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COVID-19 prompted dramatic changes in another respiratory virus

One of the first studies to document the impact of COVID-19 on already existing viruses in Australia has shown the pandemic was responsible for creating a huge change in the incidence and genetics of Respiratory Syncytial Virus (RSV) in the country.

RSV is a common virus that generally causes mild, cold like symptoms but the infection can be serious for infants and older adults.

The researchers say the pandemic disrupted the seasonal pattern of RSV, which is one of the regular ‘winter viruses’. For the first time on record, in 2020 there was no winter RSV epidemic, which is attributed to COVID-19 travel restrictions and infection control measures.

However, RSV was one of the first of the key respiratory pathogens to re-emerge after COVID-19.

The researchers genetically sequenced major outbreaks of RSV occurring out of season over the summer of 2020-21 on both sides of the country. These outbreaks coincided with the easing of COVID-19 control measures.

They found there had been a major collapse in RSV strains known before COVID-19, and the emergence of new RSV strains. These new strains dominated each outbreak in Western Australia, New South Wales and the Australian Capital Territory.

The researchers then tracked the seeding of viruses from each outbreak into Victoria, which led to another major RSV outbreak.

“Our genetic studies showed that most of the previous RSV strains had gone ‘extinct’ and that for each outbreak only a single genetic lineage had survived all the lockdowns,” said lead researcher John-Sebastian Eden, senior research fellow at the University of Sydney Institute for Infectious Diseases.

The study raises important questions as to how rapid spread and evolution of RSV could inform the re-emergence of other viruses including influenza.

“The constellation of flu strains circulating pre and post-COVID-19 has also changed a lot, leading to challenges in how we choose the composition and timing of our annual vaccines. For example, the flu season in Australia has kicked off much earlier than in previous years.” said Eden.

There is currently no approved RSV vaccine, but it is a major focus for vaccine and therapeutic development.

“We need to be vigilant – some viruses may have all but disappeared, but will likely rebound in the near future, possibly at unusual times and with stronger impact,” Eden said. “We need to be prepared for large outbreaks of RSV outside of normal seasonal periods.”

Before COVID-19, two major RSV subtypes, A and B, co-circulated at similar levels.

During late 2020 to early 2021 during the outbreak periods, this changed dramatically. The RSV-A subtype was found to be the dominant strain – making up more than 95% of cases in all the states. The RSV-B had all but disappeared.

AI reveals hidden features on chest scans of people with Long Covid

A new computer-aided diagnostic tool could help overcome some of the challenges of monitoring lung health following infection with COVID-19.

In common with other respiratory illnesses, COVID-19 can cause lasting harm to the lungs. However, it is hard to visualise this damage because conventional chest scans do not reliably detect signs of lung scarring and other pulmonary abnormalities. That is making it difficult to track the health and recovery of people with persistent breathing problems and other post-COVID complications.

The new method developed by researchers in China and at the King Abdullah University of Science and Technology, Saudi Arabia, overlays artificial intelligence algorithms on top of standard chest imaging data to reveal otherwise indiscernible visual features indicative of lung dysfunction.

As a result, radiologists can identify and analyse novel sub-visual lung lesions,” said computer scientist and computational biologist Xin Gao. “Analysis of these lesions could then help explain patients’ respiratory symptoms,” allowing for better disease management and treatment, he said.

The method first eliminates any anatomical features not associated with the lung parenchyma; the tissues involved in gas exchange that are the main sites of COVID-19–induced damage. That means removing airways and blood vessels, and then enhancing the pictures of what is left behind to expose lesions that might be missed.

The researchers trained and validated their algorithms using computed tomography (CT) chest scans from thousands of people hospitalised with COVID-19 in China.

Gao and colleagues demonstrated the tool could reveal signs of pulmonary fibrosis in people with Long COVID, thus helping to account for shortness of breath, coughing and other lung problems. He says this diagnosis would be impossible with standard CT image analytics.

Own goal: despite fewer fans and social distancing, football matches spread COVID-19 in Germany

Football matches that went ahead during the second COVID-19 wave in Germany were linked to local increases in the number of infections, despite the outdoor setting, reduced stadium occupancy and social distancing, a new study suggests.

The researchers found that local COVID-19 incidence on match days played a key role in subsequent infection levels.

Kai Fischer of the University of Düsseldorf compared counties in Germany where football matches took place with counties without matches between August and November 2020, and then looked at how infection rates evolved over time in these counties.

He found that, on average, just one additional football match in a county led to 0.34 - 0.71 additional cases per 100,000 people three weeks later. This might not sound like much, but when extrapolated to the 7-day incidence per 100,000 people, it is an increase of approximately 3-7% for just one match.

During this period, the authorities restricted the number of people who could attend matches, capping stadium occupancy levels at approximately 20%. Harsher occupancy restrictions were imposed when local weekly case numbers exceeded 35 cases per 100,000 inhabitants. Hygiene and social distancing rules also varied, with top league matches imposing stricter regulations.

Infection levels following a match were strongly linked to the local incidence of COVID-19 on the day of the match. In fact, there were very few infections after matches when the local weekly incidence was under 25 per 100,000 people.

The study used smartphone data to show that large increases in mobility occurred on match days, leading to more human interaction, and proposes that this is a possible underlying mechanism for the phenomenon.

Spanish study shows COVID-19 arrived in the US one month earlier than the official date

Researchers at the University of Alicante who are studying the global spread of the COVID-19 epidemic have published new data showing the SARS-CoV-2 virus entered the US one month earlier than the official data.

Their analysis, conducted with the University of Pennsylvania, shows that the virus likely entered through California on 28 December 2019. That is 16 days before the officially recognised entry date set by the Centres for Disease Control and Prevention, and 3 days before the first outbreak was reported by authorities in Wuhan, China.

In addition, the study provides evidence that SARS-CoV-2 on average entered each US state a month earlier than previously reflected in official data.

The data were obtained using the Retrospective Methodology to Estimate Daily Infections from Deaths methodology, which the researchers say provides more accurate estimates of the initial cases of COVID-19 in the US and has the capacity to be extrapolated to other countries to retrospectively follow the progress of the pandemic.

Harsher COVID-19 restrictions associated with faster ‘pandemic fatigue’

Between November 2020 and May 2021, adherence to COVID-19 pandemic restrictions decreased in Italy, with the fastest decreases taking place during times of the most stringent restrictions, according to a new study.

Pandemic fatigue, characterised as lower motivation to adhere to social distancing measures and adopt health protective behaviours, is a significant concern for policymakers and health officials.

From November 2020 to May 2021 in Italy, tiered restrictions were adopted to reduce the spread of COVID-19, with regions declared red, orange, yellow or white depending on the level of infection. Restrictions ranged from a night time curfew in the yellow tier to general stay-at-home mandates in the red tier.

In the new study, the researchers used large scale mobility data from Facebook and Google captured in all 20 Italian provinces to analyse the timing of pandemic fatigue. Facebook reports the change in a user’s number of movements over time, while Google data estimates the change in time spent at home.

People’s relative change in movements increased an average of 0.08% per day and time spent outside the home increased by an average 0.04% per day, leading to a more than 15% increase in relative mobility over the seven-month study period.

During times of red tier restrictions, individual mobility increased an additional 0.16% per day and time spent outside the home increased an additional 0.04% when compared to the average. This means for every 2 week period spent in the red tier, there was an additional average 3% increase in relative mobility.

The authors conclude that changes in adherence to pandemic restrictions are faster during periods characterised by the strictest levels of restrictions. Given that milder tiers have been proven to be effective in mitigating the spread of COVID-19, the researchers suggest policymakers should consider the interplay between the efficacy of restrictions and their sustainability over time.

COVID-19’s toll on global cardiac services

A new study has shown there has been global collateral damage caused by the disruption to cardiac services during the COVID-19 pandemic, with the researchers warning that problems with heart health will continue to accrue unless mitigation strategies are speedily implemented.

In the two years from December 2019, when health systems around the world were under extreme pressure and people were fearful of catching COVID-19, individuals experiencing an acute cardiac event such as a heart attack or heart failure either stayed away or could not get admitted to a hospital.

As a result there was a substantial global decline in hospital admissions of people suffering from cardiovascular disease.

In cases where people did get medical help there was, on average, more than an hour’s delay in reaching hospital or having contact with paramedics, a huge problem, given that surviving a major heart attack depends on timely and appropriate treatment.

The study by an international team led by Leeds University, is the first global assessment of the way cardiovascular services coped during the pandemic.

The researchers analysed data from 189 separate research papers looking at COVID-19's impact on cardiovascular services from 48 countries on six continents and covering a two-year period from December 2019.

Ramesh Nadarajah, lead author of the paper, said, “Heart disease is the number one killer in most countries – and the analysis shows that during the pandemic people across the world, people did not receive the cardiac care they should have received.”

The researchers warn that the disruption to cardiovascular services will leave a legacy that requires prompt action by health administrators. “Collateral cardiovascular damage from missed diagnoses and delayed treatments will continue to accrue unless mitigation strategies are speedily implemented. The deferral of interventional procedures, especially for structural heart disease, leaves many patients at high risk of adverse outcomes.”

Across the world, hospitals saw a 22% decline in people experiencing a serious heart attack, and there was 34% decline in people attending hospital with a less severe form of heart attack. The drop was not due to fewer heart attacks but fewer people attending hospital for treatment.

Globally, there was a 34% drop in heart operations and just over half (51%) of the electronic implantable devices, such as pacemakers, used to control abnormal heart rhythms were fitted when compared to the non-COVID-19 period.

AstraZeneca antibody drug retains activity against latest SARS-CoV-2 variants

While emerging variants of concern have rendered a number of antibodies against SARS-CoV-2 ineffective, new data on AstraZeneca’s Evusheld long-acting antibody combination drug show it retains neutralising activity against the Omicron variants BA.4 and BA.5, according to a new study by Oxford University.

The in vitro data on the new emerging Omicron variants are consistent with Evusheld’s neutralisation activity against previous variants of concern.

The findings are reported on the preprint server bioRxiv, in advance of peer review.

The BA.4 and BA.5, which are now the dominant variants in Africa, appear to be spreading globally in a similar pattern to earlier variants of concern. BA.4 and BA.5 have identical spike protein sequences and appear to have evolved from BA.2.

John Perez, head of late development, Vaccines & Immune Therapies at AstraZeneca, said, “By combining two antibodies with different and complementary activities against SARS-CoV-2, Evusheld was engineered from the start to outsmart the COVID-19 virus and to remain potent in the face of this virus’ ability to rapidly mutate. These findings further support Evusheld as an important option to help protect vulnerable populations such as the immunocompromised who are unable to respond adequately to COVID-19 vaccination and are at high risk for severe disease.”

Approximately 2% of the global population is considered at increased risk of an inadequate response to COVID-19 vaccination and may particularly benefit from treatment with Evusheld in advance of exposure to the virus. This includes people who are immunocompromised, such as cancer patients, transplant patients and anyone taking immunosuppressive drugs.

Long-Covid more likely to affect women than men

In what is among the largest studies of Long COVID to date, researchers at the personal genomics testing company 23andMe show it disproportionately affects women.

The study also found that about half of those with persistent symptoms are experiencing them for six months or longer. Even after a year, more than 10% of those who reported being diagnosed with Long COVID continue to have symptoms like brain fog, fatigue, and shortness of breath.

In addition, in analyses controlling for age, sex, and ethnicity, the researchers found that those who reported that they had depression or anxiety prior to COVID-19 infection had a two-fold increase in the risk of being diagnosed with Long COVID, and having a cardiometabolic disease, such as high blood pressure, coronary artery disease, type II diabetes, and high cholesterol, was associated with a 90% higher risk.

The preliminary data published by 23andme indicates that women are at least twice as likely to be diagnosed with Long COVID compared to men, even when controlling for age, ethnicity, and related health conditions. This contrasts with the overall breakdown of those infected with COVID-19, where men are much more likely to be infected than women. Men are slightly more likely to die from the virus as well.

The 23andMe study data is consistent with other studies that have found women are much more likely to develop Long COVID. More than 78% of those diagnosed with Long COVID in the study were females, compared to about 62% among those who reported not having experienced Long COVID.

Scientists do not understand the causes long COVID, nor how to best treat it. An effort to recruit patients to study the condition by the US National Institutes of Health got off to a slow start, with the agency only recruiting about 1,300 people by late March, far short of the 40,000-patient goal.

The 23andMe study included data from more than 100,000 individuals who reported contracting COVID-19. More than 26,000 said they had experienced Long COVID, and over 7,000 that they had been formally diagnosed with it.

Canadian researchers find link between pre-pandemic air pollution and COVID-19 severity

To investigate whether there was an association between long-term exposure to air pollution before the pandemic and COVID-19 severity, researchers have analysed data on all 151,105 people aged 20 years and older with confirmed SARS-CoV-2 infection in 2020 in Ontario.

They modelled historical exposure to three common air pollutants before the pandemic, of fine particulate matter, nitrogen dioxide and ground-level ozone.

The analysis, published in the Canadian Medical Association Journal, adjusted for date of diagnosis, sex and age, being part of an outbreak, essential worker status, neighbourhood socioeconomic status, health care access including previous influenza vaccination history, previous outpatient visits and other factors.

"We observed that people with SARS-CoV-2 infection who lived in areas of Ontario with higher levels of common air pollutants were at elevated risk of being admitted to the ICU after we adjusted for individual and contextual confounding factors, even when the air pollution level was relatively low," said Hong Chen of Health Canada.

They also found an elevated risk of hospitalisation with chronic exposure to particulates and nitrogen dioxide, and an increased risk of death from COVID-19 with chronic exposure to ozone.

The researchers say the results add to the growing reports linking air pollution to COVID-19 severity from other countries, including Spain and Mexico.

More research is needed to understand the mechanisms of how long-term exposure to air pollution may be influencing severity of COVID-19, the researchers say.

Genetic contribution to wellbeing increased during the pandemic

A new study by Lude Franke and colleagues at the University of Groningen, Netherlands has found that some people weathered the stress of the COVID-19 pandemic better than others, in part due to their genes.

Over the course of the pandemic, the researchers observed that a genetic predisposition to life satisfaction had an increasing influence on perceived quality of life.

How a person perceives their quality of life depends on a combination of factors that include their genes and their environment. That mix of nature and nurture makes it hard to unpick how genes contribute to feelings about quality of life, but the COVID-19 pandemic allowed Franke and his colleagues to investigate how this stressful, worldwide event interacted with a person's genetics to affect their overall wellbeing.

The team screened the genomes of more than 27,000 participants in the Netherlands who had donated genetic material to a biobank. Then they looked for connections between genetic variants and the participants' responses to a series of questionnaires about lifestyle and mental and physical health given over ten months, starting in March 2020.

The researchers found that some individuals had a genetic tendency towards better wellbeing than others during the pandemic. Additionally, as the pandemic wore on, they found that genetic tendency had an increasingly powerful influence on how those people perceived their quality of life. Moreover, the findings demonstrate that the contribution of genetics to complex traits like wellbeing can change over time.

Old antibiotic could be an effective treatment for COVID-19, say French researchers

A study by Sandrine Belouzard and Jean Dubuisson at Pasteur Institute, Lille, France and colleagues suggests clofoctol, an antibiotic that has long been used to treat bacterial lung infections may be an effective treatment for SARS-CoV-2 viral infections.

To identify potential antiviral therapies effective against COVID-19, the researchers screened a library of 1,942 approved drugs to assess if any exhibited antiviral activity against SARS-CoV-2. They selected clofoctol and tested its effects in SARS-CoV-2-infected mice.

When transgenic mice that expressed the human ACE2 receptor by which SARS-CoV-2 enters host cells were treated with clofoctol they had a decreased viral load, reduced inflammatory gene expression, and lowered pulmonary pathology. Further studies are now needed to understand the drug’s therapeutic potential in SARS-CoV-2 patients.

“The antiviral and anti-inflammatory properties of clofoctol, associated with its safety profile and unique pharmacokinetics make a strong case for proposing it as an affordable therapeutic candidate for the treatment of COVID-19 patients,” the researchers say. “The relatively low cost of this drug suggests that it is a potential clinical option for treatment of COVID-19 patients in resource-poor settings.”

Population-scale study highlights ongoing risk of COVID-19 in some cancer patients, despite vaccination

A study co-led by the universities of Oxford, Birmingham and Southampton and the UK Health Security Agency has found that while COVID-19 vaccination is effective in most cancer patients, the level of protection against COVID-19 infection, hospitalisation and death offered by the vaccine is less than in the general population and vaccine effectiveness wanes more quickly.

“We know that people with cancer have a higher risk of severe COVID-19 disease and that the immune response in cancer patients following COVID-19 vaccination is lower. However, no study has looked at vaccine effectiveness and its waning in cancer patients at a population level,” said Lennard Lee, of the Department of Oncology at Oxford University, who led the study. “We have undertaken the largest real world health system evaluation of COVID-19 in cancer patients globally.’

The study analysed 377,194 individuals with active or recent cancer who had received two doses of the COVID-19 vaccine and undergone a SARS-CoV-2 PCR test. The numbers of breakthrough COVID-19 infections and COVID-19-associated hospitalisations and deaths in this cohort of cancer patients were compared to a control population without active or recent cancer.

The overall vaccine effectiveness against COVID-19 infection in the general population after two doses of the COVID-19 vaccine over the study period was 69.8%, whereas in the cancer cohort it was slightly lower at 65.5%.

This indicates that COVID-19 vaccination is effective in most cancer patients. However, vaccine effectiveness wanes more quickly in cancer patients. At 3–6 months following the second vaccine dose, vaccine effectiveness was 61.4% in the general population, but only 47.0% in the cancer cohort.

Looking at the differences between people with different types of cancer, vaccine effectiveness is lowest and wanes most quickly in those with the blood cancers lymphoma and leukaemia.

The type of treatment that people with cancer receive also impacts both overall vaccine effectiveness and waning. In cancer patients that were treated in the last 12 months with chemotherapy or radiotherapy, vaccine effectiveness is lower and waned more by 3–6 months than in cancer patients who did not receive these treatments or were treated more than a year ago.

Peter Johnson, professor of Medical Oncology at Southampton University, said, “This study shows that for some people with cancer, COVID-19 vaccination may give less effective and shorter-lasting protection. This highlights the importance of vaccination booster programmes and rapid access to COVID-19 treatments for people undergoing cancer treatments.”

Helen Rowntree, director of research at the charity Blood Cancer UK said, “For our community, COVID-19 very much has not gone away and many people remain in their homes due to the threat of COVID-19 highlighted in this important study.”

Finnish study shows dogs can reliably detect COVID-19 infections

A study by the University of Helsinki and Helsinki University Hospital has confirmed that scent detection dogs can be taught to identify individuals with a coronavirus infection from skin swabs.

In an experimental set up at Finland’s Helsinki-Vantaa International Airport, the accuracy of the dogs in identifying the samples was 92%.

The researchers designed a triple-blind, randomised, controlled study to test the accuracy of trained scent detection dogs where neither the dog, the dog handler, nor the researcher knew which of the sniffed skin swab samples were positive and which negative.

The study also analysed factors potentially interfering with the ability of the dogs to recognise a positive sample.

In the first phase of the study, the dogs were taught to discriminate the skin swab samples of coronavirus patients from those of volunteers who tested negative. After a training period of several weeks, the dogs moved from the training centre to Helsinki-Vantaa Airport for the next stages of the study.

In the second phase of the study, four trained dogs completed a validation test to prove their discriminatory ability. During the experiment, each dog was presented with a series of 420 samples over a period of seven days.

As several parallel samples had been collected from each sample donor, each dog received an identical set of 114 coronavirus patient samples and 306 control samples for sniffing. The coronavirus status of all sample donors had been confirmed by PCR. During each testing day, the dog sniffed 20 sample tracks with three samples each, with the tracks presented in random order.

The dogs recognised the samples correctly 92% of the time. While their sensitivity to detect a positive coronavirus sample was 92 percent, their specificity was 91 percent. Only small differences in accuracy were observed between the four dogs.

The coronavirus infection being caused by virus variants was the single largest factor contributing to erroneous identification by the dogs.

“I was particularly impressed by the fact that dogs performed worse with samples we had collected from patients suffering from a disease caused by a coronavirus variant. The explanation is simple: the dogs had originally been trained with the initial wild-type virus, and thus they did not always identify the variant samples as positive. This reveals their incredible ability of discrimination,” said Anu Kantele, professor of Infectious Diseases and chief physician at the University of Helsinki and Helsinki University Hospital.

The third phase of the study involved screening passengers and staff at Helsinki-Vantaa Airport in a real-life situation. The scent dogs correctly identified 98.7% of the negative samples. The low number of coronavirus-positive samples in real-life testing prevented a proper assessment of the dogs’ performance with positive samples.

However, based on positive ‘work motivation samples’ regularly given to the dogs during this part of the study, the performance on the correctly identified positive samples also was evaluated at 98.7%. Work motivation samples are naive samples pre-collected from PCR positive patients, but not previously sniffed by dogs.

Infection with Omicron does not provide immunity from other variants of SARS-CoV-2

Omicron infection in unvaccinated individuals does not appear to provide effective immunity against other SARS-CoV-2 variants such as Delta, according to a new paper published in Nature. However, vaccinated individuals who were later infected with Omicron did show immunity against other variants.

In a study of wild-type SARS-CoV-2 (WA1), Delta and Omicron infections in a mouse model, Omicron infection was significantly milder and generated a reduced immune response compared to WA1 and Delta infection.

The researchers at the University of California, San Francisco, collected sera from the mice seven days after infection, and tested their neutralisation efficiency against WA1, Alpha, Beta, Delta and Omicron infections.

Sera from Omicron-infected mice induced neutralisation only against Omicron. By contrast, sera from Delta-infected mice showed effective neutralisation against WA1, Alpha, Beta and Delta, and some neutralisation against Omicron, and sera from WA1-infected mice showed effective neutralisation against WA1 and Alpha, and some neutralisation against Beta and Delta. These results were replicated nine days after infection.

The researchers confirmed that Omicron infection does not provide effective neutralisation against other SARS-CoV-2 variants using sera from ten unvaccinated individuals who had recovered from Omicron infection. As observed in mice, these sera showed effective neutralisation against only the Omicron variant.

However, sera from vaccinated individuals with confirmed Omicron or Delta breakthrough infection showed effective neutralisation against all variants. These findings suggest that breakthrough Omicron or Delta infections after vaccination can boost existing immunity by eliciting hybrid immunity against all variants and providing broad protection against infection.

COVID-19 vaccination after infection with SARS-CoV-2 appears to reduce Long COVID symptoms

Vaccination after infection with SARS-CoV-2 is associated with a decrease in the likelihood of Long COVID symptoms, according to a large study of UK adults.

The researcher stress that causality cannot be inferred from this observational evidence, but say vaccination, “May contribute to a reduction in the population health burden of Long COVID, at least in the first few months after vaccination.”

The analysis is based on data from the UK Office for National Statistics, covering 28,356 adults aged 18-69 years who received at least one COVID-19 vaccine dose after testing positive for SARS-CoV-2 infection.

The researchers then tracked the presence of Long COVID symptoms over a seven month follow-up period, from February to September 2021.

Long COVID symptoms of any severity were reported by 6,729 participants (24%) at least once during follow-up.

Before vaccination, the odds of experiencing Long COVID changed little over time.

A first vaccine dose was associated with an initial 13% decrease in the odds of Long COVID, but it is unclear from the data whether this improvement was sustained over the following 12 weeks, until a second vaccine dose was given.

Receiving a second vaccine dose was associated with a further 9% decrease in the odds of Long COVID, and this improvement was sustained at least over an average follow-up of nine weeks.

The researchers say, “Our results suggest that vaccination of people previously infected may be associated with a reduction in the burden of Long COVID on population health, at least in the first few months after vaccination.”

They call for further research into the long term relationship between vaccination and Long COVID, and studies “to understand the biological mechanisms underpinning any improvements in symptoms after vaccination, which may contribute to the development of therapeutics for Long COVID.”

mRNA vaccine boosters generate strong immune response after two doses of inactivated virus vaccine

New research from Karolinska Institutet shows that giving a booster shot of an mRNA vaccine to people who have received two doses of inactivated virus vaccine offers the same level of protection against COVID-19 as three doses of an mRNA vaccine.

This is significant because the relatively low cost and ease of storage of vaccines based on inactivated SARS-CoV-2 virus means they are being used in developing countries, despite the fact that they have been shown to provide lower levels of protection against COVID-19 infection than other types of vaccine.

“Our results indicate that one booster shot of an mRNA vaccine, as a complement to the cheaper but less effective inactivated vaccines, is sufficient to achieve the ‘gold-standard’ immune response measured after three doses of mRNA vaccine,” said Qiang Pan Hammarström, professor in the Department of Biosciences and Nutrition at the Karolinska, who led the study. “That would likely be a good investment - even in resource-poor countries - to protect against severe COVID-19.”

The study included 175 healthy volunteers with different vaccination histories. The researchers investigated the presence of antibodies and memory B and T cell responses against SARS-CoV-2 after vaccination and booster shots with either the Sinopharm or Sinovac inactivated vaccines, Pfizer’s or Moderna’s mRNA vaccines, or a combination of both.

The results showed that a booster shot of an mRNA vaccine given to individuals who had received two doses of inactivated vaccine strongly boosted the levels of neutralising antibodies and memory B and T cells directed against SARS-CoV-2 variants of concern, including Omicron.

The levels were markedly higher than in people receiving three doses of an inactivated vaccine, and similar to that in those who had three doses of an mRNA vaccine or a boost of mRNA vaccine after natural infection.

“Given that almost half of the COVID-19 vaccine doses distributed worldwide are inactivated vaccines, an improved mRNA booster strategy may benefit billions of people in our fight against emerging variants of concern,” said Hammarström. “A more widespread use of mRNA booster shots may also help China to [lift its] current lockdowns.”

The researchers are continuing the study, to look at the effect of the heterologous vaccination strategy on emerging Omicron subvariants of the SARS-CoV-2 virus.

“We will for the first time evaluate if this vaccination strategy can neutralise the two emerging Omicron subvariants BA.4 and BA.5, underlying the new wave of COVID-19 in South Africa,” said Hammarström.

The study was conducted within the research consortium Antibody therapy against COVID, which is funded by the European Commission.

Kidney organoids help unravel why people with diabetes at risk of severe COVID-19

Various studies have indicated that people with diabetes are more likely to develop severe COVID-19 and that more than 20% of patients hospitalised with COVID-19 suffer acute kidney damage.

However, to date, it was unknown what factors caused this to happen.

Now, an international team led by Nuria Montserrat, research professor at the Institute of Bioengineering of Catalonia (IBEC) and principal investigator of the ‘Pluripotency for organ regeneration’ group, has used bioengineering to develop mini-kidneys, or organoids, that simulate the early stages of diabetes.

The kidney organoids were used to demonstrate that the ACE2 receptor via which the SARS-CoV-2 virus enters human host cells, plays an essential role in SARS-CoV-2 infection in the kidney.

The team has also used genetic engineering to generate organoids lacking other receptors that have been identified as possible gateways for the virus. Then, using kidney cells from patients, they uncovered a possible role for energy metabolism in SARS-CoV-2 infection.

The researchers say this opens the door to the discovery of new therapies to treat COVID-19.

In diabetic kidney organoids, there is an abundance of the ACE2 receptor and this was shown to increase susceptibility to viral infection,

The researchers say it is important to understand the molecular mechanisms that underlie more severe COVID-19 in patients with diabetes and other metabolic comorbidities. The development of a diabetic kidney organoid is a step towards experimentally dissecting how metabolic changes can impact SARS-CoV-2 infections.

Their data again demonstrate that ACE2 is the essential receptor for SARS-CoV-2, even in the case of comorbidity.

Symptoms of Long COVID persisting two years after infection

Two years after infection with COVID-19, half of patients who were admitted to hospital still have at least one symptom, according to the longest follow-up study to date.

The study followed 1,192 participants in China infected with SARS-CoV-2 during the first phase of the pandemic in 2020.

While physical and mental health generally improved over time, the analysis suggests that COVID-19 patients still tend to have poorer health and quality of life than the general population. This is especially the case for participants with Long COVID, who typically still have at least one symptom including fatigue, shortness of breath, and sleep difficulties two years after initially falling ill.

The long-term health impacts of COVID-19 have remained largely unknown, with the longest follow-up studies to date only around one year after infection. The lack of pre-COVID-19 health status and comparisons with the general population in most studies has also made it difficult to determine how well patients with COVID-19 have recovered.

Lead author Bin Cao, of the China-Japan Friendship Hospital, China said, “Ongoing follow-up of COVID-19 survivors, particularly those with symptoms of Long COVID, is essential to understand the longer course of the illness, as is further exploration of the benefits of rehabilitation programmes for recovery. There is a clear need to provide continued support to a significant proportion of people who’ve had COVID-19, and to understand how vaccines, emerging treatments, and variants affect long-term health outcomes.”

The authors evaluated the health of 1,192 participants with acute COVID-19 treated at Jin Yin-tan Hospital in Wuhan, China, between January 7th and May 29th, 2020, at six months, 12 months, and two years.

Two years after initially falling ill, patients with COVID-19 are generally in poorer health than the general population, with 31% (351/1,127) reporting fatigue or muscle weakness and 31% (354/1,127) reporting sleep difficulties. In quality of life questionnaires, COVID-19 patients also more often reported pain or discomfort (23% [254/1,127]) and anxiety or depression (12% [131/1,127]) than non-COVID-19 participants.

Around half of study participants (650/1,190) had symptoms of Long COVID at two years, and reported lower quality of life than those without Long COVID.

German scientists uncover possible COVID-19 drug target

It was shown early in the pandemic that SARS-CoV-2 depends on the IFITM family of proteins that are expressed on the membranes of host cells, to enter human cells and replicate inside them. But it was not known if the same applied to the variants of concern that evolved as the infection spread around the world.

Now researchers at Ulm University medical centre have found all SARS-CoV-2 variants of concern, "remain strongly dependent” on these transmembrane proteins to replicate efficiently and to produce infectious progeny viruses.

Frank Kirchhoff, professor of virology said, “In addition, we show that an antibody against [family member] IFITM2 can protect human lung cells from SARS-CoV-2 infection. Our results suggest that IFITM2 may represent a highly unexpected target for a host-directed therapeutic approach. Targeting cellular factors in the host, rather than viral factors, reduces the risk of emergence of viral resistance.”

The researchers carried out SARS-CoV-2 infection studies in a human epithelial lung cancer cell line expressing normal and reduced levels of IFITM proteins, then measured viral replication by quantifying viral RNA and infectious virus production.

In addition, they treated human lung cells with antibodies targeting IFITM2 or the viral ACE2 receptor (used by SARS-CoV-2 to gain entry into the cell) and found that both measures inhibit SARS-CoV-2 infection.

“This has important implications for our understanding of the spread and pathogenesis of SARS-CoV-2. Additionally, our results provide insight into how SARS-CoV-2 avoids, or in this case, even exploits innate cellular defense mechanisms,” said Kirchhoff.

Long-COVID patients at increased risk of blood clots

People suffering from long COVID may face an increased risk of abnormal blood clots and researchers at University College Hospital in London have now shown this problem to be four times more likely in those experiencing difficulties with basic exercise more than 12 weeks after their COVID-19 infection.

The study, the first to report an association between abnormal blood clotting tests and reduced exercise capacity in people with Long COVID, offers important new insight into the potential mechanisms behind the longer-term effects of COVID-19 infection.

Common symptoms of Long COVID include fatigue, chest pain, shortness of breath, and brain fog. One study estimates that up to half of all people who recover from infection continue to experience lingering symptoms, but since Long COVID is an emerging condition, its biological basis is not fully understood.

The research provides insight into the underlying medical mechanisms, such as damage to cells that line blood vessels, of the disease. “By definition, this syndrome occurs when one experiences COVID-related symptoms long after the onset of infection that we can't attribute to any other cause or diagnosis,” said study author Nithya Prasannan, of the Department of Haematology at UCLH. “This study offers us laboratory and clinical evidence to begin to understand why some people experience long COVID symptoms.”

People attending an outpatient Post-COVID clinic between July 2020 and May 2021 were assessed in the study.

Researchers measured abnormal blood clotting markers by assessing the relative levels of two proteins in the body, Von Willebrand factor (VWF), a protein important in blood clotting, and ADAMTS13, a protein that cuts or splices VWF to prevent it from clogging blood vessels. If this ratio was raised, meaning that there was significantly more VWF than ADAMTS13 in the bloodstream, scientists characterised patients as being in a pro-thrombotic state, meaning that they could face a greater risk of developing blood clots.

Participants also completed exercise tests, and the researchers measured oxygen levels and tested participants’ blood before and after exercise to measure their lactate levels, which helps describe a participant’s response to exertion.

Patients who exhibited a significant decrease in oxygen levels while exercising and/or a rise in lactate afterward, were classed as having an impaired exercise capacity. Notably, patients with raised levels of blood clotting markers were also four times more likely to have an impaired exercise capacity.

“I hope that people will view this research as a step forward in understanding what causes Long COVID, which will hopefully help us guide future treatment options,” Prasannan said.

First evidence from a randomised clinical trial that second booster dose of COVID-19 vaccine is effective

A UK study investigating the immune response to a fourth dose of COVID-19 vaccine has shown immunity to SARS-CoV-2 is boosted.

The latest results from the COV-BOOST trial, show that a fourth dose of an mRNA vaccine is safe and increases antibodies to higher levels than seen after a third dose.

This is the first data from a randomised clinical study looking at the safety and efficacy of a second booster dose.

Countries including the US, Germany, Israel and the UK have been offering fourth doses to the most vulnerable, as a precautionary strategy to maintain high levels of immunity prior to data being available.

However, on 6 April the European Medicines Agency and the European Centre for Disease Control and Prevention concluded it was too early to consider using a fourth dose of COVID-19 vaccine in the general population, saying there was currently no clear evidence in the EU that vaccine protection against severe disease is waning substantially in adults with normal immune systems aged 60 to 79 years.

The COV-BOOST findings, published in Lancet Infectious Diseases, now show that a fourth dose mRNA booster is well-tolerated in people who received Pfizer as a third dose. It is also effective at increasing both antibody and cellular immunity up to and above baseline and peak levels observed following third dose boosters.

Saul Faust, professor of paediatric immunology at Southampton University, and lead of the COV-BOOST study said, “These results underline the benefits of the most vulnerable people receiving current spring boosters and gives confidence for any prospective autumn booster programme in the UK.”

In December 2021, COV-BOOST provided the world’s first data on the safety, immune responses and side effects of third dose in mix and match schedules.

In the fourth dose study, 166 people who had received a third dose of Pfizer, following Pfizer or AstraZeneca initial doses in June 2021, were randomised to receive full dose Pfizer or half dose Moderna as a fourth dose. These were approximately seven months after their third dose.

Pain at the vaccination site and fatigue were the most common side effects. There were no vaccine-related serious adverse events, and fourth doses were safe and well tolerated.

Andrew Ustianowski, National Institute of Health Research clinical lead for the COVID-19 vaccination programme said, “We knew that it was important to offer a fourth dose to those most vulnerable earlier in the year. These new study findings support that decision and provides the public with the confidence that fourth doses are both safe and even more effective than third doses at boosting immunity against COVID-19.”

People who are very obese get less benefit from COVID-19 vaccination

Adults with severe obesity generate a significantly weaker immune response to COVID-19 vaccination compared to those of normal weight, according to a study by Volkan Demirhan Yumuk, professor of medicine at Istanbul University.

This is significant because obesity is a risk factor for getting more severe disease if infected with SARS-CoV-2.

The study, presented the European Congress on Obesity in Maastricht, Netherlands last week, also found that people with severe obesity (BMI of more than 40kg/m2) vaccinated with Pfizer/BioNTech’s mRNA vaccine generated significantly more antibodies than those vaccinated with the whole inactivated SARS-CoV-2 vaccine CoronaVac, which was developed by the Chinese vaccines manufacturer Sinovac Biotech. That suggests the Pfizer vaccine might be a better choice for this vulnerable population.

Vaccines against influenza, hepatitis B and rabies, have shown similar reduced responses in people with obesity.

The researchers investigated antibody responses following Pfizer/BioNTech and CoronaVac vaccination in 124 adults (average age 42-63 years) with severe obesity who visited the Obesity Centre at Istanbul University-Cerrahpasa, Cerrahpaşa Medical Faculty Hospitals, between August and November 2021.

They also recruited a control group of 166 normal weight adults (BMI less than 25kg/m2, average age 39-47 years) who were visiting the Cerrahpasa Hospitals Vaccination Unit.

In those without previous SARS-CoV-2 infection and vaccinated with Pfizer/BioNTech, patients with severe obesity had antibody levels more than three times lower than normal weight controls.

Similarly, in participants with no prior SARS-CoV-2 infection and vaccinated with CoronaVac, patients with severe obesity had antibody levels 27 times lower than normal weight controls.

However, in those with previous SARS-CoV-2 infection, antibody levels in patients with severe obesity and vaccinated with Pfizer/BioNTech or CoronaVac were not significantly different.

“These results provide new information on the antibody response to SARS-CoV-2 vaccines in people with severe obesity and reinforce the importance of prioritising and increasing vaccine uptake in this vulnerable group,” said Yumuk.

Cognitive impairment from severe COVID-19 is equivalent to 20 years of ageing

Cognitive impairment as a result of severe COVID-19 is similar to that sustained between 50 and 70 years of age, and is the equivalent to losing 10 IQ points, according to a study by researchers at Cambridge University and Imperial College London.

The results suggest the effects are still detectable more than six months after the acute illness, and that any recovery is at best gradual.

There is growing evidence that COVID-19 can cause lasting cognitive and mental health problems, with recovered patients reporting symptoms including fatigue, ‘brain fog’, problems recalling words, sleep disturbances, anxiety and post-traumatic stress disorder, months after infection.

Between a third and three-quarters of hospitalised patients report still suffering cognitive symptoms three to six months later.

To explore this link in greater detail, researchers analysed data from 46 individuals who received in-hospital care, of whom 16 were put on mechanical ventilation, at Addenbrooke’s Hospital, Cambridge.

They underwent detailed computerised cognitive tests an average of six months after their acute illness. COVID-19 survivors were less accurate and had slower response times than the matched control population.

The effects were strongest for those who required mechanical ventilation. By comparing the patients to 66,008 members of the general public, the researchers estimate that the magnitude of cognitive loss is similar on average to that seen over 20 years ageing, between 50 and 70 years of age, and that this is equivalent to losing 10 IQ points.

David Menon of the division of anaesthesia at Cambridge University said, “Cognitive impairment is common to a wide range of neurological disorders, including dementia, and even routine ageing, but the patterns we saw – the cognitive 'fingerprint' of COVID-19 – was distinct from all of these.”

The patients’ scores and reaction times began to improve over time, but the researchers say that any recovery in cognitive faculties was at best gradual.

There are several factors that could cause the cognitive deficits, say the researchers. Direct viral infection is possible, but unlikely to be a major cause. Instead, it is more likely that a combination of factors contribute, including inadequate oxygen or blood supply to the brain, blockage of large or small blood vessels due to clotting, and microscopic bleeds.

However, emerging evidence suggests that the most important mechanism may be damage caused by the body’s own inflammatory response and immune system.

Unvaccinated people with pre-existing heart disease up to 9 times more likely to be seriously ill with COVID-19

By combining data from 110 COVID-19 studies, researchers at Queen Mary University London have found that unvaccinated individuals who contract the virus when they already have high blood pressure, diabetes or major heart damage are up to nine times more likely to suffer serious outcomes, including death, lung failure, admission to intensive care and kidney problems.

The study looked at almost 49,000 unvaccinated patients in total, and identified multiple predictors of more severe COVID-19 and worse outcomes compared to people who were vaccinated.

It found that evidence of heart muscle damage at the time of admission to hospital was associated with a nine-fold increase in likelihood of death. These patients also had higher chances of developing other complications, including severe lung failure and acute kidney injury, and to require intensive care and mechanical ventilation.

Ajay Gupta, study author and senior clinical lecturer at Queen Mary said, “These findings present a strong case for these at-risk groups to be prioritised for vaccinations and other preventative measures.”

EU-funded project in Italy shows online misinformation led to vaccine hesitancy in the US

Online misinformation had a negative impact on the US COVID-19 vaccination campaign, according to an EU-funded study by Francesco Pierri, researcher at the Politecnico di Milano, carried out in collaboration with Indiana University.

The objective of the study, which was part of the EU’s €9.9 million Periscope project, was to determine whether or not there are statistically significant associations between the quality of information consumed online and “anti-vax” sentiment in the US, with consequent repercussions on the vaccination campaign.

The study confirmed a statistically significant association between the amount of misinformation shared online and the tendency to refuse or delay vaccination. In the states and counties where the most online misinformation is consumed, there is greater vaccination hesitancy and, consequently, lower vaccination coverage.

Since the beginning of 2021, researchers at the Politecnico di Milano have collected millions of posts shared on Twitter related to vaccines, with the aim of studying the effects of unreliable and/or inaccurate information on the US vaccination campaign, which began at the end of 2020.

Using a list of news sites tagged by journalists, fact-checkers, and other academics as portals spreading false and unreliable news, the researchers identified millions of posts with potentially harmful content, for example articles claiming that vaccines don't work or cause death, shared by millions of Twitter users in early 2021 across the US.

In order to measure people's willingness or not to get vaccinated, the researchers used millions of responses to daily polls administered on Facebook in which they asked users in the US whether or not they intended to get vaccinated.

Pierri said the results, “show that the proportion of misinformation shared on average by users in a given area is positively correlated with the proportion of people who declare they have no intention of getting vaccinated and, similarly, negatively correlated with the number of vaccine doses administered.”

Periscope is a €9.9 million project involving a consortium of 32 European institutions, which is investigating the implications of COVID-19 in a broad way, including the socio-economic impacts, health impacts and the impacts on health systems.

Use of available public health data would have led to stricter COVID-19 controls in Sweden

In a controversial approach, Sweden was the only country in Europe not to have a lockdown during the first wave of the COVID-19 pandemic in 2020. Now, a new study by Xiaoqin Wang and colleagues at the University of Gävle has shown that the country’s public health agency had data on hand which if analysed at the time, would have led to stricter control measures.

One of the main criticisms of the COVID-19 Commission, which was set up to look at Sweden’s response to the pandemic, was that early protective measures were belated and failed to prevent or even significantly reduce the spread of the infection in the country.

The new analysis shows that if public health agency data which was available early had been used and analysed, it would very likely have resulted in a more restrictive strategy with tougher infection control measures.

“The opportunity was not taken to use available data to determine the outcome of Sweden’s strategy. As a result, COVID-19 mortality rates in Sweden are exceptionally high compared to our Nordic neighbours,” Wang said.

Decisions during the earliest period of the pandemic were based on subjective judgements and later, when more data became available, mathematical analyses were only focused on achieving herd immunity, the researchers note.

“Due to dubious interpretations, only less invasive infection control measures were introduced in Sweden, even at the arrival of the second wave, leading to significantly higher mortality rates compared to the other Nordic countries,” the researchers conclude.

Citizen science project guides Long COVID research agenda in Switzerland

As the pandemic progresses the number of people living with Long COVID is increasing, but it remains unclear how and why Long COVID develops, whether it can be prevented, and how it is best treated.

Now a team of scientists at the University of Zurich’s Epidemiology, Biostatistics and Prevention Institute has joined forces with representatives of two patients’ groups, Long COVID Switzerland and the Long COVID Network, to form the Long COVID citizen science board.

The aim is to amplify the voice of people with Long COVID in order to get greater understanding of the condition and drive research to improve healthcare and the development of treatments.

“Collaborative projects that bring together different stakeholders allow us to grasp the impact of such a new disease and hopefully effectively tackle the challenges for people living with Long COVID,” said Milo Puhan, professor of epidemiology and public health at the university.

The research team recruited the Long COVID citizen science board, whose members met online to discuss their needs and identify the most relevant research areas, acting as citizen scientists in co-shaping the study’s direction, analysis and findings.

The study found that people affected by Long COVID and their families need answers to a long list of 68 questions, which fall into four areas: medical, for example, risk factors, diagnosis and treatment; healthcare services; socio-economic factors, such as the impact on work and finances; and disease burden.

Through an online survey, the research team asked the citizen scientists and 241 other people affected by Long COVID to rate and prioritise these 68 questions.

“The scientists empowered us to define those research topics which have the largest impact on our health and lives. Not surprisingly the results reflect our top concern, which is that we still lack effective therapies,” said Chantal Britt, founder and president of Long COVID Switzerland.

The researchers hope this study will guide funding of future Long COVID research, and say that given the limited resources it is important to prioritise the areas of most relevance to those who are affected by the condition. Contacts

Europe-wide study shows vaccination campaigns need to be tailored

A study in eight European countries has shown that public health information on the benefits of vaccines has in some cases reduced the willingness to get immunised against COVID-19.

Taken overall, COVID-19 vaccination campaigns in Europe did not live up to the hopes of the public health authorities. However, earlier studies in various countries have yielded a mixed picture as to which communication strategies increase vaccine uptake and which factors undermine certain messages.

A team of the Technical University of Munich (TUM), the University of Trento and the London School of Economics explored these questions in Bulgaria, France, Germany, Italy, Poland, Spain, Sweden and the UK.

During the intensive phase of the vaccination campaigns, April - June 2021, more than 10,000 unvaccinated adults were initially provided online with general information on the available vaccines. Then they received one of three messages combining text and images, or were assigned to a control group.

Message 1 highlighted the efficacy of the available vaccines in reducing the risk of serious illness and death through COVID-19.

Message 2 stressed the advantages of having a vaccination certificate, especially for travel.

Message 3 presented the prospect of leisure-time activities without restrictions, for example restaurant and cinema visits, access to fitness studios and attendance at concerts.

The participants were then asked whether they intended to be vaccinated against COVID-19 if given the opportunity during the following week.

The study, published in Science Advances, shows that the text messages would be effective in boosting vaccination quotas only in Germany and, to a lesser extent, in the UK. In Germany vaccination willingness was significantly higher in the three groups than in the control group. In the UK, the readiness was higher only when the message stressed the benefits of a vaccination certificate.

In all other countries the messages were ineffective, or even produced results opposite to those intended: people in Spain and Italy, when informed of the reduced risk of illness through vaccines, were less likely to seek vaccination than the corresponding control groups.

Using data mining methods, the researchers carried out detailed analysis of various associations between the message effectiveness and sociodemographic characteristics, as well as the following factors: citizens’ trust in their government; health literacy; and the share of the population who believe in certain conspiracy theories.

For all messages, the likelihood of achieving the desired effect was reduced in countries where the health literacy of the population was low. “This result surprised us,” said Matteo Galizzi, professor of behavioural science at the London School of Economics. “We had thought that understandable and clearly visualised information on COVID-19 would lead to an improved understanding of the disease among people with little prior knowledge and thus to a greater vaccination willingness.”

In contrast, the study confirmed conjecture that citizens’ trust in their own government would have a positive effect on vaccination intention.

“During the pandemic, people often looked at other countries to see what was working better or worse. Our study showed that such comparisons have limited usefulness,” said professor Tim Büthe, chair of International Relations at TUM. “A more promising approach is to investigate the existing conditions in every country and then adapt the policy measures and communication strategies accordingly. Policy makers can use our findings to inform messaging for upcoming COVID-19 booster campaigns.”

DOI

10.1126/sciadv.abm9825

New tool for assessing the symptoms of Long COVID

Researchers at Birmingham University have worked with patients experiencing Long COVID to develop a tool that can capture symptoms and assess the impact on quality of life.

More than 200 symptoms are associated with Long COVID, which in many cases is affecting people for months after the original SARS-CoV-2 infection has gone. The symptoms can involve many organs in the body and include breathlessness, fatigue and brain fog. It is estimated Long COVID affects more than 100 million people worldwide.

Reliable ways of measuring these symptoms are needed to inform the development of new therapies and ensure patients get the best possible care.

To address this, a team from the Centre for Patient-Reported Outcomes Research at Birmingham University has designed the Symptom Burden Questionnaire for Long COVID. Patients can use it to report symptoms and the data can be used to help identify current drugs that are potential treatments and to test whether new drugs are safe and effective.

“People living with Long COVID say they experience a huge range of symptoms, but getting these recognised by healthcare practitioners and policy-makers has been a struggle,” said one of the researchers, Sarah Hughes. “We designed and tested this tool with our patient partners to ensure it is as comprehensive as possible, while also not being burdensome for patients to complete.”

The resulting questionnaire measures different symptoms of Long COVID and the impact of these symptoms on daily life. It was developed with extensive patient input following regulatory guidance, meaning its scores may be used to support regulatory decisions around the approval of new therapies for Long COVID and by policymakers.

Shielding not a substitute for lockdowns

Shielding those vulnerable to COVID-19, while allowing the virus to spread through the rest of the population, would have failed according to a new modelling paper by scientists at Bath University.

The economic and social costs of COVID-19 control measures, especially lockdowns, have been high. An alternative and widely discussed public health strategy was to ‘shield’ those most vulnerable to COVID-19, minimising their contacts with others while allowing infection to spread among lower risk individuals, with the aim of reaching herd immunity.

Shielding strategies or “focused protection” would have been impossible to implement in practice and would have likely led to far worse outcomes, according to the research. Even if implemented perfectly, the modelling reveals that allowing the infection to spread through less vulnerable groups prior to vaccination would have overwhelmed health care capacity in the UK and led to tens of thousands of unnecessary deaths.

In reality, practical considerations would have meant that large numbers of vulnerable people who were supposed to be protected would also have died.

The researchers assessed a hypothetical large city in England with a population of one million inhabitants. They compared the outcomes from no shielding, with imperfect and perfect shielding, with shielding restrictions lifted when cases fall below a given threshold.

The research concludes that while shielding may have protected the vulnerable in theory, it required extremely restrictive conditions that were impossible to achieve in practice.

For example, because shielding in real populations would have been imperfect, infections in the lower-risk population would have leaked through to vulnerable people who were shielding. In addition, if lower-risk individuals reduced social contact to avoid infection it may have been impossible to achieve herd immunity, meaning a second wave of infections would have occurred after shielding had ended.

There is would also be an even greater healthcare burden associated with the large number of cases of Long COVID. Waning immunity, and new variants would only have served to make a shielding-only strategy even more untenable.

The researchers say that although vaccines are now available and have been successfully rolled out in many countries, modelling studies are critical to determine whether shielding would have been a viable strategy for dealing with COVID-19, or, indeed, the next pandemic. Many countries have poor vaccine coverage and so the choice between shielding and measures that are more restrictive at a population level is likely to remain for some time. In future, new variants may continue to emerge that are able to escape immunity, which may require a renewed choice between lockdowns and shielding.

Despite the success of vaccination programmes, the recent omicron wave shows that we are not out of the woods yet,” said one of the authors Ben Ashby. “If in future a new variant emerges that substantially escapes existing immunity, then it’s possible we may have to choose between lockdowns and shielding once again (or indeed, in future pandemics). Although lockdowns are costly for many reasons, attempting to shield the vulnerable while letting the virus spread through the rest of the population is far worse.”

Not changing gloves at COVID-19 testing centres in Belgium may have inflated infection figures

A lack of glove changes at COVID-19 testing centres in Belgium led to major cross-contamination of samples and a high rate of false positive results, according to research presented at the European Congress of Clinical Microbiology & Infectious Diseases in Lisbon this week.

The need for rapid roll-out of large-scale PCR testing for COVID-19 presented a number of logistical challenges, including a scarcity of personnel adequately trained to do nasopharyngeal swabbing.

Research from a government-funded lab in Belgium has identified inadequate management of personal protective equipment in testing centres as a source of major cross-contamination.

Scientists at the COVID-19 Federal Platform, Department of Laboratory Medicine UZ Leuven, were alerted to the problem in September 2021 when they noticed that 70% of samples taken that day at a testing centre in Brabant, Flanders, had tested positive for COVID-19. The average positivity rate at the time was around 5-10%.

Of the positive samples, 90% had a very low viral load, which hinted that they had been contaminated with the SARS-CoV-2 virus, rather than being true positives.

The results were withheld and an investigation into the cause of the spike in positive samples carried out.

“After excluding lab contamination, we arranged the results from that day in chronological order by time of sample collection,” said lead researcher Bram Slechten. “We saw that no one had tested negative after a sample was collected from a patient with a very high viral load.

This led them to identify lack of glove changing, in combination with high-paced collection of samples by someone who was new to the job, and the breaking of a swab, as the likely source of the contamination.

Protocols were tightened up overnight and all those whose results were withheld were recalled for a new sample the next day, with all testing negative.

To assess the scale of the problem, Slechten and colleagues retrospectively checked four months of results, from June-Sept 2021, of PCR tests from 11 testing centres for false positives.

The analysis identified potential cross-contamination events in 73% (8/11) of the test centres. The percentage of samples suspected of being wrongly reported as positive widely varied each day and for each centre. The four-month average ranged from 0% to 3.4% per testing centre.

The highest number of false positives at one testing centre on a single day was 77 of 382 tests, 20% of people tested.

Site visits confirmed a lack of glove changes between one patient and the next as being the source of cross-contamination.

“If the staff didn’t change gloves between each patient, it was almost certain that contamination would occur,” said Slechten. “We identified four reasons why changing of gloves didn’t happen: it was simply not in the protocol; correct protocol was in place but it was not followed due to lack of training of new members of staff; not having the right size of glove available; and work pressure - some swabbers had to sample one patient every two minutes.”

More rigorous policies were put in place at all 11 testing centres from the end of October 2021, in response to the study results.

Follow-up of one test centre revealed the impact. Before the intervention, it had a daily positivity rate of 11% and an average false positivity rate of 3.4%. But occasionally, the false positive rate rose to 20%. After the intervention, the false positive rate fell to almost zero.

Slechten believes the false positives artificially inflated the COVID-19 case numbers for Belgium, but said, “It is hard to put a number on it however, because we saw a lot of differences between the test centres we studied. In addition, we only looked at test centres in one part of Belgium, making it hard to get the whole picture.”

It is very probable that this same cross contamination also occurred in other countries.

“While I don’t have detailed knowledge of the protocols in testing centres in other countries, the focus is generally on potential events within the lab environment. However, our research provides a perfect example of the importance of looking beyond the lab and keeping an eye on the entire testing chain,” Slechten said.

Of more than 2,000 patients hospitalised with COVID-19 only around 1 in 4 fully recovered after one year

The possible toll of long COVID is highlighted in a new UK study of more than 2,000 patients who were hospitalised with COVID-19, which shows that a year after having COVID-19, only around one in four patients feel fully well again.

The research, presented at the European Congress of Clinical Microbiology & Infectious Diseases in Lisbon this week and published in the Lancet Respiratory Medicine, shows being female, being obese and having had mechanical ventilation in hospital were all associated with a lower probability of feeling fully recovered at one year.

The most common ongoing long-COVID symptoms were fatigue, muscle pain, physically slowing down, poor sleep, and breathlessness.

The researchers used data from the post-hospitalisation COVID-19 (PHOSP-COVID) study which assessed adults who had been hospitalised with COVID-19 across the UK. Patients from 39 hospitals were included, who agreed to five-month and 1-year follow-up assessments in addition to their clinical care.

Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge. The researchers also took samples of participants’ blood at the five month visit to analyse it for the presence of various inflammatory proteins.

A total of 2,320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 completed both the 5-month and 1-year visits at the time of analysis (the study is ongoing).

These 807 patients had a mean age of 59 years, 279 were women and 28% received invasive mechanical ventilation. The proportion of patients reporting full recovery was similar between 5 months at 26% of 1,965 and 1 year, at 29% of 804.

In an earlier publication from this study the authors had identified four clusters of symptom severity at five months, which were confirmed by this new study at one year.

“The limited recovery from 5 months to 1 year after hospitalisation in our study across symptoms, mental health, exercise capacity, organ impairment, and quality-of-life is striking,” said researcher Louise Wain of the National Institute for Health Research at Leicester University. “No specific therapeutics exist for long COVID and our data highlight that effective interventions are urgently required,” she said.

Without effective treatments, long COVID could become a highly prevalent new long-term condition, the researchers said.

Longer intervals between COVID-19 vaccination boost antibody response

New research presented at the European Congress of Clinical Microbiology & Infectious Diseases in Lisbon this week shows that a longer interval between primary COVID-19 vaccine doses can boost antibody production up to nine-fold.

To find out factors affecting antibody responses following Pfizer/BioNTech vaccination, Ashley Otter and colleagues at the UK Health Security Agency (UKHSA) measured antibody levels in blood samples taken from almost 6,000 healthcare workers from across the UK.

Of these, 3,989 had their first dose of the vaccine at least 21 days earlier, while 1,882 had their second dose at least 14 days earlier. The participants were classified by infection history as either previously having had COVID-19, or naïve, with no history of infection. Almost all of those who hadn’t had COVID-19 generated antibodies against the virus on vaccination.

After dose 1, those with previous infection had up to ten times higher antibody levels than naïve individuals, whilst after dose 2, those with previous infection had antibody levels more than twice as high as those who hadn’t had previous infection.

Looking at dosing intervals, it was found that a longer dosing interval was associated with antibody levels that were up to nine times higher in naïve participants, with a more pronounced effect observed in younger participants.

Regardless of timing between infection and vaccination, all individuals mounted a very high antibody response after dose 2.

“This study shows that a longer time between vaccine dose 1 and dose 2 results in higher antibody responses in naïve participants,” Otter said. “We’ve also shown that in those with previous infection, timing between exposure and vaccination plays a critical role in post-vaccination antibody responses.”

Further research is needed to determine whether these higher antibody levels provide greater protection against COVID-19, and how longer dosing intervals affect the response to boosters, Otter said.

Swiss scientists show COVID-19 vaccination greatly reduces infectious viral load

Scientists at the University of Geneva have provided direct evidence that COVID-19 vaccination not only protects individuals from SARS-CoV-2 infection, but also reduces the spread of disease, including of the highly transmissible Omicron BA1 variant.

While diagnosis of COVID-19 using a PCR test is very effective in identifying infected people, it does not indicate whether they are infectious and capable of transmitting the virus to other people, said Isabella Eckerle, who led the research, published in Nature Medicine. “However, [understanding] of contagiousness is essential for deciding on collective prevention measures, such as periods of isolation,” she said.

PCR tests detect the presence of viral RNA, but do not indicate whether the virus is still intact and able to spread. The measurement of the infectious viral load necessarily involves culturing the virus for several days in a biosafety level 3 laboratory, a procedure impossible to perform routinely.

Since the beginning of the pandemic, samples taken at the University Hospital of Geneva screening centre have been kept for research purposes, enabling the scientists to re-analyse samples from previous waves of infection. They measured the infectious viral load of three cohorts of patients during the first five days of symptoms, to compare the viral load caused by the original virus that first emerged in Wuhan, China (118 samples, spring 2020), the Delta variant (293 samples, autumn 2021) and the Omicron variant sublineage BA.1 (154 samples, winter 2022). In addition, for the second and third cohorts, the researchers looked to see whether a significant difference could be detected in vaccinated and unvaccinated individuals.

Overall, the infectious viral load for the Delta cohort was significantly higher than the cohort with the original virus.

However, people infected by Delta who received two doses of mRNA vaccine had a significantly lower infectious viral load than unvaccinated people.

“For the Omicron cohort, contrary to what can be assumed given its rapid spread, the infectious viral load was overall lower than that of the Delta cohort,” said Eckerle. However, only people who were boosted with a third dose of vaccine had a decreased viral load; people who had received two doses only had the same viral load as unvaccinated people.

“This is immunologically consistent: many vaccines require three doses spaced several months apart to induce a sustained immune response,” Eckerle said.

This begs the question of why the Omicron variant is so contagious, if the viral load it induces is lower than its predecessors. “We still don’t know, but our data suggest that other infectious mechanisms are at play,” said Pauline Vetter, clinic director of the University of Geneva Centre for Emerging Diseases. “It is now clear that the mutations of Omicron strongly differentiate it from other variants, allowing it to partially escape the vaccine, and diminish the effectiveness of some antiviral treatments used so far,” she said.

The Geneva study shows that knowledge acquired for previous variants must be updated every time a new variant emerges, to be able to adapt the means of combating COVID-19. “In view of our results, the greatest caution should be exercised in the face of a virus whose evolution is not fully understood, and against which currently existing treatments lose some of their effectiveness,” the paper concludes.

Combination therapy best at treating severe COVID-19

First line treatments for patients hospitalised with COVID-19 include monoclonal antibodies to neutralise the SARS-CoV-2 virus and the steroid drug dexamethasone, which has strong anti-inflammatory properties.

Researchers in Berlin have now studied the mechanisms of action of both types of treatment and found evidence to suggest that combination therapy of antibodies and dexamethasone is more effective than either of these treatments alone.

The researchers tested the effects of single and combined antiviral and anti-inflammatory therapies in two hamster models of COVID-19, looking at the extent of lung tissue damage and the quantities of infectious virus and viral RNA present in the tissues at various time points.

This enabled them to check whether and how viral activity might change over the course of treatment. They found clear evidence of synergistic action when monoclonal antibodies and dexamethasone are administered in combination.

Using single-cell analyses, it was shown that antibodies are effective at reducing the amount of virus present. However, it is not the virus that damages the lung tissue, but the strong inflammatory response the virus triggers. That is where dexamethasone takes over, suppressing the immune system and preventing an escalation of the immune response.

The best treatment outcomes were achieved when the researchers administered a combination of antiviral and anti-inflammatory treatments. This type of combination therapy is not included in existing clinical guidelines, and what is more, current guidance says that in high-risk patients, antibody therapy can only be given in the first seven days following symptom onset.

In clinical practice, dexamethasone is only used once a patient requires oxygen therapy, at an extremely advanced stage of the disease. Its use in combination with antibodies however, opens entirely new treatment time windows.

This new approach must now be evaluated in clinical trials before it can be adopted in clinical practice, the researchers say.

Moderna data point to more effective COVID-19 booster vaccines

Moderna has published new clinical data on its bivalent COVID-19 booster platform including its first bivalent booster candidate, mRNA-1273.211, which includes mutations found in the Beta variant, several of which persist in more recent variants of concern, including Omicron.

A booster dose of mRNA-1273.211 provided protection against Beta, Delta and Omicron variants one month after administration, and continued to be effective six months after administration for Beta and Omicron variants.

“We believe that these results validate our bivalent strategy,” said Stéphane Bancel, CEO of Moderna. They indicate mRNA-1273.211 induces higher antibody responses than a booster dose of Moderna’s original monovalent vaccine mRNA-1273, even though it is not specifically designed to protect against the variants that have emerged since Beta.

"Our latest bivalent booster candidate, mRNA-1273.214, which combines the currently authorised Moderna COVID-19 booster with our Omicron-specific booster candidate, remains our lead candidate for the fall 2022 northern hemisphere booster,” Bancel said.

Moderna is developing updated booster vaccines to address the continued evolution of the SARS-CoV-2 virus, including monovalent and bivalent candidates targeting multiple variants of concern. The company has multiple bivalent booster candidates that have been evaluated to date, including mRNA-1273.211, which has nine spike protein mutations based on the Beta variant, and mRNA-1273.214, which has 32 spike protein mutations based on the Omicron variant.

German government awards €7.4M grant for COVID-19 trial

German biotech company Adrenomed announced that adrecizumab, its treatment for severe COVID-19 infections, is to get funding of €7.4 million from the German Federal Ministry of Education and Research as part of government initiatives to promote the clinical development of COVID-19 drugs.

The University Medical Centre Eppendorf Hamburg and Adrenomed will use the money to conduct a phase II clinical trial of adrecizumab in hospitalised patients with moderate to severe COVID-19. The grant will also support manufacturing of the drug for a phase III clinical trial.

Adrecizumab is a first-in-class antibody that is in development for treating of loss of blood vessel integrity in sepsis and septic shock. Similar dysregulation of the endothelial barrier is also a common feature of COVID-19 and leads to vascular leakage and severe impairment of lung and other organ functions.

In a novel precision medicine approach, patients with elevated levels of adrenomedullin, the target of adrecizumab, will be treated with the drug.

Another biomarker (dipeptidyl peptidase-3, DPP3) will used to exclude patients with complications that make them unsuitable for treatment with adrecizumab.

The phase II trial will enrol more than 200 patients with moderate to severe COVID-19 and elevated adrenomedullin levels.

Stefan Kluge, director of the department of Intensive Care Medicine at the Hamburg University medical centre, said there is an urgent need for therapies that can be used in severe cases and can be given at later disease stages. “Adrecizumab could potentially be a therapy that can address this treatment gap,” he said.

In a previous named-patient programme with critically ill COVID-19 patients treated with Adrecizumab, there was a rapid improvement in organ function.

The funding commitment of €7.4 million from the BMBF is a significant endorsement of Adrenomed’s biomarker-guided precision medicine approach for patients in the acute care setting, said Richard Jones, CEO of Adrenomed. “This clinical study further compliments our overall development programme of adrecizumab for the treatment of loss of vascular integrity in sepsis and septic shock,” he said.

CEPI partners with NEC to develop AI-designed coronavirus vaccine

The Coalition for Epidemic Preparedness Innovations (CEPI) and the Japanese electronics company NEC, have joined forces in the latest funding award under CEPI’s $200m programme to advance the development of vaccines that provide broad protection against SARS-CoV-2 variants and other betacoronaviruses.

CEPI will provide seed funding of up to $4.8 million to NEC OncoImmunity, a Norway-based subsidiary of NEC, which specialises in applying artificial intelligence to drug design, to support the initial development of a broadly protective coronavirus vaccine.

NEC will lead a research consortium, including the European Vaccine Initiative (EVI) and Oslo University Hospital, to deliver preclinical proof of concept for the vaccine, which will be based on the mRNA technology that underpins the approved Pfizer/BioNTech and Moderna COVID-19 vaccines.

NEC will apply its experience and capabilities in AI-powered design of vaccines, which will be complemented with insights from vaccine development against known coronaviruses including SARS-CoV, SARS-CoV-2 and MERS-CoV.

If this approach is successful, it may also be applicable to the development of vaccines against other pathogens in the CEPI portfolio, including ‘Disease X’, the unknown pathogen(s) with pandemic potential that have yet to emerge.

“Our experience with COVID-19 has taught us that an ideal vaccine must remain robust against an ever-evolving viral landscape. Our AI will assess viral regions that do not mutate rapidly and are shared among SARS, SARS-CoV-2, MERS-CoV and other known coronaviruses,” said Richard Stratford, CEO of NED OncoImmunity.

“I am confident that our unique approach in identifying and selecting antigens that could elicit broader cytotoxic T cell and antibody responses is well positioned to help create broadly protective betacorona virus vaccines,” Stratford said.

NEC is the first Japanese company to be involved in CEPI's work promoting vaccine development. In February 2022, the government of Japan announced a new contribution of $300 million to CEPI over the next five years.

Through COVID-19, coronaviruses have now demonstrated their devastating pandemic potential. The emergence of a coronavirus combining the transmissibility of COVID-19 with the lethality of SARS or MERS would be catastrophic, so developing vaccines that provide broad protection against the whole betacoronavirus genus is therefore vital to global health security. CEPI is working with partners to advance work in this area as quickly as possible.

The award is the eighth programme to be funded by CEPI to advance the development of broad spectrum vaccines as part of a 5-year plan, published in March 2021.

CEPI to set up global vaccines network that can rapidly respond to future threats

CEPI has announced plans to create a network of existing vaccine facilities that will work to develop, produce, store, and test vaccine candidates in response to new infectious disease outbreaks.

The initiative is intended to support CEPI’s goal of having the capabilities to develop vaccines in 100 days in response to disease outbreaks.

Existing vaccine developers and production sites are now being invited to express their interest in being part of the network.

The facilities selected by CEPI will be called upon to respond to an emerging infectious disease outbreak by rapidly manufacturing and supplying vaccine for clinical testing or mass vaccination. CEPI will offer support with workforce training and matching vaccine developers with manufacturers, so that facilities are ready to quickly manufacture at scale.

Preparing facilities ahead of future outbreaks will support CEPI’s goal of shortening the time taken to develop future vaccines to 100 days, or a third of the time it took to develop the first COVID-19 vaccine.

At the same time this will improve vaccine production capacity and capability in regions currently underserved, or with no such provision.

The sites will be globally distributed, enabling rapid access to vaccine doses worldwide, with a focus on improving access to doses in low- and middle- income regions. It could also allow for vaccine production to take place closer to the source of an outbreak, thereby potentially enabling faster vaccine distribution where it is needed.

CEPI aims to keep the vaccine facilities sustainable and ‘warm’ during inter-pandemic periods, by asking the network to support development and production of vaccines against endemic diseases like Lassa fever or yellow fever.

An expression of interest is open for developers, manufacturers, and government agencies. Applications will be initially reviewed against a set of criteria. Additional funding may be provided to facilities where there are current gaps in their set-up.

CEPI expects to identify facilities by November 2022, and aims to establish up to seven high potential facilities over the next 2 years as part of the network.

European Medicines Agency says it is too early for second booster of COVID-19 vaccine

EMA and the European Centre for Disease Control and Prevention have concluded it is too early to consider using a fourth dose of COVID-19 vaccine in the general population.

However both agencies agreed that a fourth dose, or second booster, can be given to adults 80 years of age and above, after reviewing data on the higher risk of severe COVID-19 in this age group and the protection provided by a fourth dose.

There is currently no clear evidence in the EU that vaccine protection against severe disease is waning substantially in adults with normal immune systems aged 60 to 79 years, but the data will continue to be monitored to determine if there is an increasing risk of severe illness among those who are vaccinated.

National authorities will also consider local data in deciding whether to use a fourth dose in those people at higher risk.

For adults below 60 years of age with normal immune systems, there is currently no conclusive evidence that vaccine protection against severe disease is waning or that there is an added value of a fourth dose.

Re-vaccination campaigns could start in the autumn, when there will be consideration of the best timing for additional doses. There may possibly be updated versions of vaccines by then.

So far, no safety concerns have emerged from the studies on additional boosters.

As of the end of March 2022, 83% of adults had received full initial vaccinations and only 64% had received a booster dose.

Evidence of the effectiveness of a fourth dose comes largely from Israel, where data indicate that a second booster given at least four months after first booster restores antibody levels without raising any new safety concerns. Data also suggest that a second booster provides additional protection against severe disease, although the duration of the benefits is not yet known and the evidence is still limited.

Details of the evidence assessed is in the joint ECDC-EMA statement on second boosters.

New COVID-19 vaccine could be effective against all viral variants

New preclinical data for a COVID-19 vaccine developed at the Medical University of Vienna indicates that it is effective against all SARS-CoV-2 variants known to date, including Omicron.

The antigen-based vaccine developed by a team led by Rudolf Valenta at the Centre for Pathophysiology, Infectiology and Immunology, targets the receptor binding domain (RBD) of the SARS-CoV-2 virus, inducing a robust and uniform RBD-specific IgG antibody response in animal models and in human serum samples. The antibody response prevents the virus from docking onto and entering the body's cells, so that infection cannot occur.

The vaccine has the potential, “to induce sterilising immunity to old and new SARS-CoV-2 variants by stopping viral replication and transmission through the inhibition of cellular virus entry,” said Valenta.

It is expected that the vaccine will be effective in people who have not previously responded to vaccination, as it will generate additional T-cells.

The development of the Austrian COVID-19 vaccine was inspired by decades of previous in allergy vaccine design.

"Our data give us grounds to hope that this readily producible protein-based vaccine antigen will be effective against all SARS-CoV-2 variants known to date, including Omicron," Valenta said. "The vaccine is designed to enable repeated injections to build up sustained sterilising immunity, is suitable for use in all age and risk groups, and appears to be superior to currently available vaccines when it comes to inducing neutralising antibodies."

If sufficient funding is forthcoming, the first clinical trials could be carried out this year.

Nudges worked when COVID-19 control measures were not feasible or enforceable

Throughout the COVID-19 pandemic, so-called nudges prompted people to adopt simple behaviours in the name of public health.

These include fist bumps in place of shaking hands and standing six feet apart.

This indicates insights from behavioural science can inform the design of effective behaviour change techniques, to influence individual behaviour.

Ivo Vlaev at Warwick University worked with members of the UK government’s Behavioural Insights Team to develop Mindspace, a framework that was used to guide effective policy drawing on the latest insights from behavioural sciences and nudge theory.

In a paper reviewing the use of Mindspace during the early months of the pandemic, Vlaev and co-authors highlight examples of nudges used in the early months of the COVID-19 pandemic and summarise their effectiveness.

The evidence is that nudges work and are a powerful social science tool amidst a pandemic.

“Organisation leaders, policymakers, and practitioners can use nudges to promote public health when mandates are not politically feasible or enforceable,” the paper says.

Benefits of less pollution and noise during lockdown cancelled out by fall in physical activity

The lockdown measures imposed across Europe in March 2020 to contain the COVID-19 pandemic led to unprecedented declines in air pollution and noise, but also of physical activity levels in cities.

The consequences of these changes for people's health differed depending on the stringency of the confinement measures and local context, according to new research by the Barcelona Institute for Global Health.

To compare different contexts, the research team looked at three European cities with different degrees of lockdown: Barcelona, where a strict lockdown was imposed including law-enforced home confinement; Stockholm, where the measures were much more relaxed and subject to individual responsibility; and Vienna, which had intermediate measures.

For each of the three cities, they collected or estimated data on air pollution, noise and physical activity from three different points in time: before the pandemic, during lockdown and in the subsequent period when restrictions were relaxed.

It was shown that the strictness of the confinement measures was directly related to the decline in exposure to noise and pollution and amount of exercise. Barcelona, the city facing the greatest restrictions was also the one that recorded the largest decreases in air and noise pollution and physical activity. Specifically, during the first lockdown, nitrogen dioxide concentrations fell by 50% on average, daily noise levels were reduced by 5 decibels and physical activity was reduced by 95%.

During the same period, in Vienna, NO2 pollution fell by 22%, and average daily noise levels were reduced by 1 decibel, while physical activity fell by 76%.

For Stockholm, NO2 levels fell by 9%, noise levels were reduced by 2 decibels and physical activity fell by 42%.

Drawing on evidence from previous studies, physical activity was the main driver of health outcomes, the researchers conclude. Extending strict confinement in Barcelona for a full year would have resulted in a 10% increase in strokes and heart attacks and an 8% and 12% increase in diagnoses of depression and anxiety, respectively, due to the reductions in physical activity.

Reduction of physical activity in Vienna for a whole year could have led to a 5% increase in the annual incidence of strokes and heart attacks, as well as 4% and 7% increase in diagnoses of depression and anxiety, respectively.

Even in Stockholm, the city with the slightest decline in physical activity levels, there would have been negative health effects if the situation had lasted for a year. The model estimated a 3% increase in the respective incidences of strokes and heart attacks, 2% more diagnoses of depression and 3% additional cases of anxiety.

On the other hand, if the reduction in NO2 concentrations from the first lockdown had been sustained for a whole year, an estimated 5% of heart attacks, 6% of strokes and 11% of depression diagnoses could have been prevented in the city of Barcelona. In Vienna, the estimated decreases would be 1% for strokes and heart attacks and 2% for depression.

In Stockholm the positive health impact would be the prevention of 1% of depression diagnoses.

Lower noise levels over one year in Barcelona could have prevented an estimated 4% of annual heart attacks, 7% of strokes and 4% of diagnosed depression. In Vienna, the incidence of myocardial infarction, stroke and depression could have been reduced by 1%. And finally, for Stockholm, a 2% reduction in diagnosed heart attacks and depression, and a 4% reduction in stroke cases related to noise reduction is estimated.

“Despite the differences observed in the three cities, there is a common pattern: the health benefits of improved air quality and noise fail to offset the profoundly negative effects of reduced physical activity levels,” said Sarah Koch, first author of the study.

Easy, accessible and cheap test picks out the most at-risk COVID-19 patients

An electrocardiogram (ECG) can pinpoint those hospitalised COVID-19 patients who are at high risk of death and might need intensive management, according to a study presented at the European Heart Rhythm Association meeting in Copenhagen on Monday.

Specifically, the research showed that a prolonged QT interval – a measure of the electrical activity of the heart - is an independent risk factor for both myocardial injury and one-year mortality.

“An ECG is an inexpensive, non-invasive, easily attainable and widely available test applied in nearly all hospitalised patients,” said Ariel Banai of Tel Aviv Sourasky Medical Centre, Israel. “Our study suggests that a simple ECG tracing performed upon admission may help healthcare professionals to triage patients with COVID-19 and identify those in need of intensive care.”

The QT interval refers to the electrical signal from the moment the ventricles of the heart contract until they finish relaxing, and is measured in milliseconds. Patients with a prolonged QT interval are at increased risk for life-threatening arrhythmias (heart rhythm disorders) and cardiac arrest.

This study examined the association between QT prolongation and long-term mortality in patients hospitalised with COVID-19. It also evaluated the relationship between prolonged QT interval and myocardial injury, in which cells in the heart die.

A total of 335 consecutive patients hospitalised with COVID-19 were prospectively studied. All patients had an ECG upon admission.

At one year, 41% of patients in the prolonged QT interval group had died, compared to 17% in the normal QT interval group.

Banai said, “In our study, one-third of hospitalised COVID-19 patients had a prolonged QT interval. These patients were generally older and sicker, but even after adjusting for these factors, prolonged QT interval was independently associated with worse survival. More studies are needed to confirm our observations, but the results indicate that ECG assessment could play a role in the risk stratification of patients admitted with COVID-19 infection.”

Deer in Germany and Austria have not contracted SARS-CoV-2, unlike their North American cousins

SARS-CoV-2 has spread from humans to white-tailed deer in North America and the animals are now considered reservoirs from which the virus could spill back to humans.

However, a team headed by researchers at the Leibniz Institute for Zoo and Wildlife Research has now shown this has not happened in Germany and Austria, and all deer tested were negative for SARS-CoV-2 antibodies.

The spread from humans to deer is a cause of concern, since novel variants could evolve in the new deer host and eventually spill back to humans. While white-tailed deer are a North American species, deer occur worldwide, and in central Europe like North America, are heavily hunted and managed.

The scientists examined blood samples from 433 roe, red and fallow deer, both pre-pandemic and collected during the pandemic, for SARS-CoV-2 antibodies using an assay that previously confirmed antibody levels in North American deer. None of the deer from Germany or Austria were positive.

The team also compared the ACE2 receptor via which the virus enters host cells. With the exception of one change which might potentially make red deer somewhat more resistant to infection, no changes were found in the receptor in the European species that could account for the difference in results between central European and North American deer exposure.

The likely explanation for the differences relates to how deer are distributed and managed in North America compared to central Europe. In North America, deer are often peri-urban and urban, with high potential levels of contact with humans and human waste. Deer are managed principally by the federal government.

In Germany and Austria, deer are generally not peri-urban or present in urban settings and the system for granting hunting licenses mean deer in a specific area are locally managed. These factors limit human-deer contact and also hinder the spread of pathogens among deer populations.

“Every effort should be made to maintain barriers to human-deer contact in central Europe to prevent the establishment of deer as a SARS-CoV-2 reservoir,” said Alex Greenwood, co-author of the paper describing the research.

Austrian study finds COVID-19 can have long term effect on the lungs

Some people who recover from COVID-19 pneumonia have evidence of damage to their lungs that persists a full year after the onset of symptoms, according to a new study by clinicians in Austria.

While COVID-19’s short-term effects on the lungs are well documented, much less is known about any long-term effects.

The researchers looked at patterns and rates of improvement of chest CT abnormalities in patients one year after COVID-19 pneumonia. They assessed 91 participants, mean age 59 years, at several points over one year after the onset of symptoms.

At one year, abnormalities were present in 49 participants. Of these, 49 two had received outpatient treatment only, 25 were treated on a general hospital ward and 22 had received intensive care.

“The observed chest CT abnormalities from our study are indicative of damaged lung tissue,” said study co-author Anna Luger of the Department of Radiology at Innsbruck Medical University. “It is currently unclear if they represent persistent scarring, and whether they regress over time or lead to pulmonary fibrosis.”

While the abnormalities decreased in initial follow-up, 63% of those affected did not show any further improvement after six months.

Evidence from the SARS-CoV-1 outbreak of 2002 to 2004 shows that lung abnormalities may remain detectable even after decades, but do not show any progression. However, more recent studies have shown a risk of progression.

“We were able to show that the severity of acute COVID-19, protracted systemic inflammation and the presence of residual chest CT abnormalities are strongly related to persistently impaired lung function and clinical symptoms,” said study co-author Christoph Schwabl of Innsbruck Medical University.

UV-LED lights can kill coronaviruses

Lightbulbs that are already in use in offices and public spaces can destroy coronaviruses and HIV, according to a new study from Toronto University.

Researchers killed both viruses using UV-LED lights, which can alternate between emitting white light and decontaminating ultraviolet light. With a cheap retrofit, they could also be used in many standard lighting fixtures, giving them a “unique appeal” for public spaces, said Christina Guzzo, senior author of the study.

Guzzo first tested the lights on bacterial spores that are notorious for their resistance to ultraviolet light.

“If you're able to kill these spores, then you can reasonably say you should be able to kill most other viruses that you would commonly encounter in the environment,” Guzzo said.

Within 20 seconds of UV exposure, growth of the spores dropped by 99%.

The researchers then created droplets containing coronaviruses, to mimic typical ways people encounter viruses in public, from coughing and sneezing. The droplets were then exposed to UV light and placed in a culture to see if any of the virus remained active. With just 30 seconds of exposure, the virus’ ability to infect dropped by 93%.

Guzzo also compared UV light to two heavy duty disinfectants used in lab research, showing UV lights were similarly effective in their ability to deactivate viruses.

“I was really surprised that UV could perform on the same level of those commonly used lab chemicals, which we regard as the gold standard,” Guzzo said.

UV-LEDs are cheap and could be easy to retrofit in existing light fixtures, and the bulbs are long-lasting and simple to maintain.

However, repeated, prolonged exposure to UV radiation is harmful. Guzzo suggested UV lights should be used when public spaces are empty, such as vacated buses that have finished their routes, or empty elevators. Escalator handrails could be continuously disinfected by putting UV lights in the underground part of the track, cleaning it with each rotation.

Safe Antivirus Technologies, a Toronto-based start-up company that worked with Guzzo on the study, is developing UV-LED lighting modules with motion sensors. The lights automatically switch to UV light when a room is empty, then turn back to regular light when there is movement.

Apply COVID-19 rules to clinical trials derailed by war in Ukraine, EMA says

The European Medicines Agency (EMA) is advising companies running clinical trials affected by the war in Ukraine to use the experience gained during the COVID-19 pandemic and apply the same approaches and flexibilities.

More than one month after the war started, this is the first advice from the European Commission, the EMA and the heads of national medicines agencies on how to manage the conduct of clinical trials in Ukraine.

EMA says certain changes and protocol deviations in the current situation are unavoidable, when for example scheduled study visits cannot take place, or arrangements need to be made to transfer trial participants who are fleeing Ukraine to other investigator sites of the same trial in the EU.

Clinical trial sponsors have also asked for guidance on how to handle the situation in terms of trial records, documentation, data collection, protocol deviations, and missing data with its potential impact on methodological aspects.

Karolinska researchers develop new method for discovering nanobodies against emerging COVID-19 variants

Scientists at the Karolinska Institutet say they have developed a new way of discovering antibody fragments, called nanobodies, against emerging SARS-CoV-2 variants.

They have found multiple nanobodies that block infection with different SARS-CoV-2 variants in human cells and mice.

Despite the roll-out of vaccines and antivirals, the need for effective therapeutics against severe COVID-19 infection remains high. Nanobodies offer several advantages over conventional antibodies because they have a long half life in the blood stream, are better able to penetrate tissues and are easier and cheaper to manufacture.

In a paper published in Nature Communications, the researchers describe a single nanobody, Fu2, that significantly reduced the viral load of SARS-CoV-2 in cell cultures and mice. Using electron cryomicroscopy, they found that Fu2 naturally binds to two separate sites on the viral spike protein, thus inhibiting the virus’ ability to enter the host cell.

A second paper in Science Advances describes additional nanobodies that in cell cultures and mice effectively cross-neutralised both the founder and beta variant of SARS-CoV-2 and the more distantly related SARS-CoV-1.

The researchers are now applying the same techniques to identify nanobodies that are able to neutralise the Omicron variant.

Catching flu and COVID-19 causes greater risk

Adults in hospital who have COVID-19 and the flu at the same time are at much greater risk of severe disease and death compared to patients who have COVID-19 alone, according to new research.

Patients co-infected with SARS-CoV-2 and influenza were over four times more likely to require ventilation support and 2.4 times more likely to die than if they only had COVID-19.

Researchers say this shows there is a need for more flu testing of people admitted to hospital with COVID-19.

The team from Edinburgh, Liverpool and Leiden universities and Imperial College London, made the finding based on more than 305,000 hospitalised patients with COVID-19.

The research, which is part of the International Severe Acute Respiratory and emerging Infection Consortium’s Coronavirus Clinical Characterisation Consortium, is the largest ever study of people with COVID-19 and other endemic respiratory viruses.

Kenneth Baillie, professor of experimental medicine at Edinburgh University said, “We found that the combination of COVID-19 and flu viruses is particularly dangerous. This will be important as many countries decrease the use of social distancing and containment measures. We expect that COVID-19 will circulate with flu, increasing the chance of co-infections. That is why we should change our testing strategy for COVID-19 patients in hospital and test for flu much more widely.”

Different SARS-CoV-2 variants cause different long COVID symptoms

New research that is due to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in Lisbon, Portugal, 23-26 April, suggests the symptoms connected to long COVID could be different in people infected with different variants.

The study is by Michele Spinicci and colleagues from the University of Florence and Careggi University Hospital in Italy.

Estimates suggest that over half of survivors of SARS-CoV-2 infection experience long COVID. The condition can affect anyone, old and young, otherwise healthy, and those with underlying conditions. It has been seen in people who were hospitalised with COVID-19 and those with mild symptoms.

The researchers carried out a retrospective observational study of 428 patients treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2 and the Alpha variant were circulating in the population.

At least three-quarters of patients reported at least one persistent symptom.

Researchers compared the symptoms reported by patients infected between March and December 2020, when the original SARS-COV-2 was dominant, with those reported by patients infected between January and April 2021, when Alpha was the dominant variant and discovered a substantial change in the pattern of neurological and cognitive/emotional problems.

They found that when the Alpha variant was the dominant strain, the prevalence of muscle aches and pain, insomnia, brain fog and anxiety/depression significantly increased, while anosmia (loss of smell), dysgeusia (difficulty in swallowing), and impaired hearing were less common.

“Many of the symptoms reported in this study have been measured, but this is the first time they have been linked to different COVID-19 variants”, said Spinicci. “The long duration and broad range of symptoms reminds us that the problem is not going away, and we need to do more to support and protect these patients in the long term.”

Immune response shown to protect unvaccinated healthcare workers from COVID-19

Despite daily contact with COVID-19 patients early in the pandemic, some health professionals avoided falling ill. Now, a University of Gothenburg study has shown they were protected by immunoglobulin A (IgA) antibodies.

To understand how the immune system builds up its defences against COVID-19, researchers at the university’s Sahlgrenska Academy monitored 156 employees at five primary care health centres, for six months.

None of them had been vaccinated against COVID-19, and most of them met infected patients daily.

“We thought it was important to investigate what happened when completely healthy people encountered the coronavirus, before vaccines became available,” said Christine Wennerås, professor of clinical bacteriology at the Sahlgrenska.

Those staff who did not contract the disease had high levels of IgA in their respiratory tracts. These antibodies, found naturally in the secretions of mucous membranes in the airways and gastrointestinal tract, bind to viruses and neutralise them.

One in ten protected

The study showed that a third of the care workers developed antibodies to COVID-19. These subjects fell into two distinct groups, based on antibody patterns and COVID-19 incidence.

One group, who had IgA antibodies only, never succumbed to COVID-19, while the other group, which had IgG antibodies and T cells against SARS-CoV-2, did contract the infection.

“We all have IgA. It’s found on the mucous membranes, and COVID-19 is an infection that spreads via those membranes,” Wennerås said.

The study aimed to identify health factors that appeared to afford protection against COVID-19. Numerous factors were found by means of questionnaires, blood tests and more.

What all the subjects who neither tested positive, nor fell ill, had in common, were IgA antibodies.

A lot of the COVID-related research has focused on IgG antibodies and T cells, Wennerås noted. “The interesting thing is that when we now examine other people's articles and tables, we find evidence for the conclusion we’ve arrived at about IgA. But it’s not something those studies have highlighted,” said Wennerås.

Self-monitoring of oxygen levels can help anticipate serious COVID-19 infections

Measuring blood oxygen levels at home with pulse oximeters is a safe way for people with COVID-19 to spot signs their health is deteriorating and they may need emergency care, according to new research.

It is known that a fall in blood oxygen levels is a critical indicator of severe COVID-19 infection. Now, a study led by Imperial College London’s Institute of Global Health Innovation, has provided the first extensive evidence review of the use of pulse oximeters in home monitoring for people with COVID-19.

It looked at 13 studies involving almost 3,000 participants across five countries, most of which were carried out during the first wave of the pandemic.

The review indicates that with medical guidance, home pulse oximetry can act as a safety net, reducing unnecessary emergency and hospital admissions for patients who can safely stay at home, while spotting early signs of deterioration and escalating care for those who need it.

However, there is a shortage of research on darker skinned patients, for whom oximetry may be less accurate than in white people.

Based on their findings, the researchers put forward recommendations to help standardise the use of oximetry in home COVID-19 monitoring.

This includes the use of a defined cut-off point in blood oxygen levels of 92%, at which professional care should be sought.

Ahmed Alboksmaty, research associate at the Institute of Global Health Innovation said, “Our study shows that people with COVID-19 can safely keep an eye on their blood oxygen levels at home using pulse oximetry. If their oxygen levels drop below a certain point, then this indicates that they need to seek professional medical care.”

Some smartphones and mobile apps also have the capability to measure blood oxygen levels. However, while a number of studies have reported similar accuracy to traditional pulse oximeters, the researchers concluded there is not enough evidence yet to recommend their use for clinical monitoring.

People infected with Omicron remain infectious for as long as with other COVID-19 variants

While the Omicron variant appears to be less harmful than previous variants in terms of severity of disease, hospitalisations and deaths, a virology expert told a special COVID-19 meeting of the European Congress of Clinical Microbiology & Infectious Diseases on Wednesday that the evidence so far shows that the period of infectiousness with Omicron is not convincingly shorter than with other variants.

Studies using culturable virus as a marker for infectiousness indicate people with the Omicron variant are infectious from around 2 days before symptoms appear, to 7 days after.

“The decisions being made by different countries around the world to shorten the period of isolation for Omicron infections are partly based on evidence from modelling, but also take account of the fact that Omicron is causing less severe disease, and fewer hospitalisations and deaths,” said Marjolein Irwin-Knoester of the University Medical Centre Groningen, Netherlands. “From the evidence so far, I am not convinced that a person is likely to be infectious for a shorter period of time with Omicron as they would have been with previous variants.”

At a recent time point - and with the situation ever-evolving - required isolation periods varied from four days in Norway and Denmark, to five days in the Netherlands and UK, seven days in Belgium, Spain and vaccinated people in France, to ten days in Germany and unvaccinated people in France.

The legal requirements to isolate have also changed in some jurisdictions. For example, in the UK, there is no longer a legal requirement to self-isolate with COVID-19, it is now just a recommendation.

While there is some evidence that vaccination decreases the time of shedding of infectious virus, the evidence around this subject is conflicting. However, for Omicron, the beneficial effect of vaccination on reducing infectiousness is likely to be lower, most probably due to mismatch between currently designed vaccines and the Omicron variant.

Anti-ageing drug could be treatment for COVID-19

BioAge Labs, a biotech developing drugs that address the molecular causes of ageing, announced its clinical stage oral drug BGE-175, which targets age-related immune deficiencies, protects aged mice from lethal infection with SARS-CoV-2.

In the study, published in Nature, daily doses of BGE-175 prevented death in aged mice infected with a lethal dose of SARS-CoV-2. Ninety percent of mice that received the drug survived, whereas all untreated control mice died.

BGE-175 treatment was initiated two days after infection, when the mice were already ill, mirroring a situation in which a patient receives medication only after developing symptoms.

In both humans and animals, immune function declines with age, increasing the severity of COVID-19 in people over 65. Unlike antivirals for treating COVID-19, BGE-175 corrects these age-related immune deficits rather than targeting the virus.

The drug acts by inhibiting a protein which BioAge has identified as a key target for immune aging. Through this pathway, BGE-175 boosts dendritic cells that help the body identify pathogens and decreases neutrophil infiltration that leads to damaging inflammation, thus combating the decline in immunity that makes older people more vulnerable to infection.

A phase II clinical trial is underway in the US, Brazil, and Argentina to determine whether BGE-175 can prevent respiratory failure and mortality in patients over 50 years of age hospitalised with COVID-19.

French research shows COVID-19 vaccination is not associated with recurrence of myocarditis

A small study has shown that SARS-CoV-2 vaccination in patients who had an inflamed heart muscle (myocarditis) in the past is not associated with a recurrence of the condition or other serious side effects.

“These results provide reassuring data that may encourage patients with a history of myocarditis to get vaccinated against SARS-CoV-2,” said study author Iyad Abou Saleh of Hospices Civils de Lyon, France. “It should be noted that the majority of patients in our study received the [Pfizer/Biontech] vaccine and therefore the findings may not apply to other vaccines.”

Rare cases of myocarditis following SARS-CoV-2 vaccination have been reported in the scientific literature with a prevalence of 2.1 cases for 100,000 people. However, there is a lack of data regarding the risk of myocarditis recurrence after SARS-CoV-2 vaccination in patients with a history of the condition.

“Our experience shows that in some situations patients have avoided vaccination because they, or their GP, were afraid it could cause another bout of myocarditis,” Abou Saleh said.

The researchers included all patients hospitalised in Hospices Civils de Lyon during the last five years (from January 2016 to June 2021) with a diagnosis of acute myocarditis.

A total of 142 patients with a prior history of confirmed acute myocarditis were enrolled in the study. The average age was 31 years and 20.3% were women. Among them, vaccination status was known for 71 patients (50%): 55 patients were vaccinated and 16 were not vaccinated. The main reason given for not getting the vaccine was the fear of myocarditis recurrence (12 patients, 75% of non-vaccinated patients). Vaccination status was unknown for 66 patients and five patients had died before the COVID-19 outbreak.

“We showed that SARS-CoV-2 vaccination in patients with a history of acute myocarditis is not associated with a risk of recurrent myocarditis or other serious side effects,” said Abou Saleh.

COVID-19 infection increases the risk of type 2 diabetes

A new study has shown that people who have had Covid-19 are at increased risk of developing type 2 diabetes.

This follows on from earlier research showing that the pancreas can be affected by SARS-CoV-2 and that following a COVID-19 infection, reduced numbers of insulin secretory granules in beta cells and impaired glucose-stimulated insulin secretion have been observed.

In addition, after COVID-19, some patients developed insulin resistance and had elevated blood glucose levels, even though they had no previous history of diabetes.

SARS-CoV-2 infection may lead to activation of the immune system that can persist for months, and which impairs insulin effectiveness.

To date, however, it was unclear whether these metabolic changes are transient or whether COVID-19 increases the risk of diabetes. To investigate this question, researchers from the German Diabetes Centre, the German Centre for Diabetes Research and the health data company IQVIA conducted a retrospective cohort study.

The study included 1,171 physician practices across Germany and ran from March 2020 to January 2021, covering 8.8 million patients. Follow-up continued until July 2021.

As a control group, the researchers selected people with acute upper respiratory tract infections (AURI), which are also frequently caused by viruses. The two cohorts were matched for sex, age, health insurance, month of COVID-19 or AURI diagnosis, and comorbidities (obesity, hypertension, high cholesterol, heart attack, stroke).

During the study period, 35,865 people were diagnosed with COVID-19 and the analysis showed they were more likely to go on to develop type 2 diabetes than people with AURI.

The incidence of diabetes with COVID-19 infection was 15.8 compared to 12.3 per 1,000 people per year with AURI, meaning that the relative risk of developing type 2 diabetes was 28% higher in the COVID-19 group than in the AURI group.

COVID shown to have long term effect on memory

Seven in ten long COVID patients experience concentration and memory problems several months after the initial onset of their disease, with many performing worse than their peers on cognitive tests, according to new research from Cambridge University.

Half of the patients in the study reported difficulties in getting medical professionals to take their symptoms seriously, perhaps because cognitive symptoms do not get the same attention as lung problems or fatigue.

The findings are among the first results of an online study called ‘COVID and Cognition’ monitoring the symptoms of 181 long COVID patients over 18 months. The majority suffered COVID-19 at least six months before the study began. Very few people had been ill enough with COVID-19 to be hospitalised. A further 185 people who have not had COVID-19 are involved in the study as controls.

Of the 181 long COVID patients, 78% reported difficulty concentrating, 69% reported brain fog, 68% reported forgetfulness, and 60% reported problems finding the right word in speech. These self-reported symptoms were reflected in significantly lower ability to remember words and pictures in cognitive tests.

Participants carried out multiple tasks to assess their decision-making and memory. These included remembering words in a list, and remembering which two images appeared together. The results revealed a consistent pattern of ongoing memory problems in those who had suffered COVID-19 infection. Problems were more pronounced in people whose overall ongoing symptoms were more severe.

People who experienced fatigue and neurological symptoms, like dizziness and headache, during their initial illness were more likely to have cognitive symptoms later on. They also found that those who were still experiencing neurological symptoms were particularly impaired on cognitive tests.

“This is important evidence that when people say they’re having cognitive difficulties post-COVID, these are not necessarily the result of anxiety or depression. The effects are measurable; something concerning is happening,” said Muzaffer Kaser, a researcher in the Department of Psychiatry at Cambridge University and a consultant psychiatrist, who was involved in the research.

Italian research finds COVID-19 vaccines are safe for people who are immunocompromised

People with impaired immunity are at high risk of severe complications from COVID-19, but there is also uncertainty about the safety and effectiveness COVID-19 vaccines.

A new study in carried out in Italy has found the two mRNA-based vaccines are well tolerated by these high-risk patients. The trial found that the vaccines were safe and did not cause unexpected adverse events in a group of patients with various cancers, neurological, and rheumatological conditions that are associated with immunosuppression.

The original clinical trials for COVID-19 vaccines were conducted in healthy volunteers. While this is standard practice, it means that high-risk immunocompromised patients, such as those taking immunosuppressant drugs for neurological conditions, were not included in the trials.

The study enrolled 566 high-risk patients in the trial, and administered two doses of either the Pfizer-BioNTech or Moderna mRNA vaccine. The patients reported any adverse events in a questionnaire.

The most common reported side-effects were also commonly reported by people with a fully functioning immune system who have received the vaccine. The study also found no evidence that the underlying disease of the patients was affected, and vaccination did not interfere with the patient’s ability to undergo standard treatment for their conditions.

Antibodies elicited by COVID-19 vaccines can still bind to the Omicron variant

The Omicron variant of SARS-CoV-2 can partially evade vaccine immunity, but a new study of 38 vaccinated individuals has shown that three leading vaccines still elicit antibodies that can bind to the virus.

The discovery suggests that vaccines can still protect against Omicron through immune mechanisms besides neutralising antibodies, potentially explaining the relative mildness of Omicron infections in vaccinated individuals.

Omicron rapidly became the dominant SARS-CoV-2 variant due to its very high transmissibility and its ability to infect people who have received vaccines. Although the virus can evade the neutralising antibodies elicited by vaccines, vaccinated individuals have a far lower chance of hospitalisation or death.

In addition, death rates haven’t climbed at the same rate as case counts during the rapid spread of Omicron worldwide, suggesting that vaccines may be providing protection through various immune mechanisms.

The researchers examined the binding activity of antibodies in plasma samples from 11 individuals who received the Moderna vaccine, 14 individuals who received the Pfizer vaccine, and 13 individuals who received the Chinese Sinovac vaccine.

Although many vaccine-induced antibodies failed to bind to the Omicron variant’s receptor binding domain, they still showed some ability to bind to the viral spike protein. Furthermore, non-neutralising antibodies that help activate the innate immune system could still bind to the spike protein across all 3 vaccines.

COVID-19 symptoms vary by geography and underlying disease

Researchers at Imperial College London found that symptoms of COVID-19, including the initial triad of cough, fever and loss of smell, varied by both country and presence of underlying health conditions like asthma and diabetes.

They say this is the first study to explore symptoms among those who test positive for COVID-19 by location and underlying chronic disease, but are not so seriously ill they are admitted to hospital.

It involved analysis of data on symptoms self-reported by 78,299 individuals in 190 countries between April and September 2020. Of these, 64,699 were symptomatic and untested, 7,980 tested positive, and 5,620 tested negative.

The researchers say the study creates a framework for using global self-reported data to identify parallels between health conditions, world region, and symptom profile of infectious diseases.

Joint senior author Aldo Faisal, professor in the departments of Computing and Bioengineering at Imperial, said understanding symptom variation by location and health is crucial for clinical practice. “It could help speed up diagnosis, predict outcomes more precisely and target treatment, particularly with the emergence of new variants."

Global snapshots can help to inform treatment of patients, whose age and underlying health conditions like asthma or diabetes are likely to affect COVID-19 symptoms and outcomes. The approach could also help to inform public health messaging and practice by monitoring in real-time the effects of new outbreaks or variants.

The symptom mapper was advertised primarily on social media and surveyed both tested and untested individuals, so that countries with poor testing infrastructure could still be included. The data represent a snapshot of symptoms from the early stage of the pandemic and relate only to the initial SARS-CoV-2 strains circulating between April and September 2020 and not the subsequent Delta and Omicron variants.

Most responses were from India (22.5%), Mexico (16.8%), Pakistan (9.5%), Philippines (9%), UK (5.7%), and Brazil (5.5%). The researchers used the machine learning technique of clustering to identify similarities between the symptom profile of different countries and underlying health conditions.

Respondents who tested positive for COVID-19 were more likely to report joint pain, loss of appetite and loss of smell and taste, than responders who had tested negative, or had symptoms but had not been tested. Fewer respondents who had tested positive for COVID-19 reported sore throat and nasal congestion than those who had tested negative or had symptoms but were untested.

Respondents with underlying lung conditions and/or type 2 diabetes were more likely to report several symptoms than those with no underlying conditions. However, loss of smell and taste was more likely to be reported as a symptom amongst COVID-19 positive responders with no underlying disease.

Respondents in Brazil were five times more likely to report chest pain and joint pain than other countries. Respondents in Pakistan were four times more likely to report chest pain and five times more likely to report joint pain. Respondents in India were three times more likely to report chest pain and four times more likely to report joint pain.

The UK symptom profile differed from the majority of countries, which the researchers say could be because its respondents were overall older than those of other countries.

The research provides a global snapshot of symptoms, an approach that could help to track variation in symptoms and identify changes linked to future variants or vaccination status.

First author Balasundaram Kadirvelu, of the Department of Computing, said, “Although many around the world have been hospitalised, most people who contract COVID-19 treat it at home with no clinical contact. These self-reported data allow us to capture the symptom profiles of patients not in contact with health services. In doing so, they offer a new perspective on the pandemic.”

Study finds long lasting inflammatory immune response after mild COVID-19 infection

A new study from Karolinska Institutet, the Helmholtz Center Munich and the Technical University of Munich has demonstrated that immune system macrophages show altered inflammatory and metabolic expression several months after mild COVID-19.

“We can show that the macrophages from people with mild COVID-19 exhibit an altered inflammatory and metabolic expression for three to five months post-infection,” said Craig Wheelock, of the Department of Medical Biochemistry and Biophysics at the Karolinska. “Even though the majority of these people did not have any persistent symptoms, their immune system was more sensitive than that of their healthy counterparts,” he said.

Long-term symptoms are relatively common after severe COVID-19 infection but may also affect people who had mild disease. More research is needed to understand the long-term immune aberrations in patients who have recovered from the infection, the researchers say.

They analysed blood samples from 68 people who had mild COVID-19 infection and a control group of 36 people who had not had COVID-19, isolating and sequencing macrophages to measure active genes. The researchers also measured eicosanoid signalling molecules, which are a fundamental feature of inflammation.

“It is not surprising to find a large number of eicosanoid molecules in people with COVID-19 as the disease causes inflammation, but it was surprising that they were still being produced in high quantities several months after the infection,” Wheelock said.

Serious COVID-19 linked to long lasting mental health problems

A new study published in The Lancet Public Health indicates serious COVID-19 illness is linked to an increase in the risk of long-term adverse mental health effects.

The findings suggest that, on the whole, non-hospitalised patients with a SARS-CoV-2 infection were more likely to experience depressive symptoms up to 16 months after diagnosis, compared to those never infected.

Patients who were bedridden for seven days or more had higher rates of depression and anxiety, compared to people who were diagnosed with COVID-19, but never bedridden.

The analysis finds that symptoms of depression and anxiety mostly subsided within two months for non-hospitalised patients with COVID-19. However, patients who were bedridden for seven days or more remained at increased risk of depression and anxiety over the 16-month study period.

Most studies to date have only examined adverse mental health impacts for up to six months after a COVID-19 diagnosis, and little is known about the long-term mental health impacts beyond that period, particularly for non-hospitalised patients with varying degrees of illness severity.

The analysis drew upon data from seven cohorts across Denmark, Estonia, Iceland, Norway, Sweden, and the UK and included 247,249 people.

Overall, participants diagnosed with COVID-19 had a higher prevalence of depression and poorer sleep quality compared to individuals who were never diagnosed (20.2% vs 11.3% experienced symptoms of depression; and 29.4% vs 23.8% experienced poor sleep quality; equivalent to an 18% and 13% increase in prevalence respectively after adjusting for other factors including but not limited to age, gender, education, body mass index, and previous psychiatric diagnosis.

Study author Unnur Anna Valdimarsdóttir, professor at the University of Iceland, said, “Our research is among the first to explore mental health symptoms after a serious COVID-19 illness in the general population up to 16 months after diagnosis. It suggests that mental health effects aren’t equal for all COVID-19 patients and that time spent bedridden is a key factor in determining the severity of the impacts on mental health.”

New coating on air filters can kill SARS-CoV-2 and other pathogens for months

Researchers at Birmingham University have developed a new antimicrobial technology for air filters which can kill bacteria, fungi and viruses, including SARS-CoV-2, in seconds, providing a potential means of preventing the spread of airborne infections.

A paper published in Scientific Reports reports on the testing of air filters coated with the chemical biocide chlorhexidine digluconate and how its antimicrobial action compares to standard filters commonly used in industrial air condensing units, and on passenger trains.

In the laboratory, cells of the Wuhan strain of SARS-CoV-2 were added to the surface of both the treated and control filters and measured at intervals over a period of more than an hour. While much of the virus remained on the surface of the control filter for an hour, all SARS-CoV-2 cells were killed within 60 seconds on the treated filter.

To determine how effective the filters are in a real-world setting, both the control and treated filters were installed in heating, ventilation and air conditioning systems on train carriages. The filters were installed for three months in matched pairs across carriages on the same train line, before being removed and shipped for researchers to analyse colonies of bacteria trapped on them.

The trial found no pathogens survived on the treated filter, even after three months on the train. Further tests also found the treated filters are durable, and are able to maintain their structure and filtration function over the lifetime of their use.

Felicity de Cogan of the Institute of Biology and Infection at Birmingham University, who is a co-author of the paper, said most ventilation systems recycle air through the system, and the filters currently being used in these systems are not normally designed to prevent the spread of pathogens, only to block air particles. “This means filters can actually act as a potential reservoir for harmful pathogens,” she said. “We have been able to develop a filter treatment which can kill bacteria, fungi and viruses, including SARS-CoV-2, in seconds.”

Other novel filters, ranging from high efficiency particulate air filters used in aerospace cabins, to UV light and silver nanoparticles added to filter mesh, have been developed to purify air. However, they have shortcomings, including not being energy efficient, or being slow to be exert their effect, meaning they are not suitable for the majority of existing heating, ventilation and air conditioning systems, which would require significant infrastructure upgrades to use them.

“In comparison, the technology we have developed can be applied to existing filters and can be used in existing heating, ventilation and air conditioning systems with no need for the cost or hassle of any modifications,” de Cogan said.

New study points to possible cause of shortage of breath post-COVID

Long-lasting immune activity in the airways could be the cause of persistent breathlessness following COVID-19, according to a new study of 38 people who had been hospitalised with severe COVID-19.

The results, published in the journal Immunity, indicate these patients have an altered landscape of immune cells in their airways and signs of ongoing lung damage. However, the preliminary results suggest that this might improve over time.

The researchers say that their findings need to be confirmed by a larger study, but that anti-inflammatory drugs could possibly speed recovery

Co-author James Harker, senior lecturer in respiratory science at Imperial College London said, “Our study found that many months after SARS-CoV-2 infection, there were still abnormal immune cells in the airways of patients with persistent breathlessness. We also identified a protein signature in the lungs indicating ongoing injury to the airways.”

The findings suggest that persistent breathlessness in the cohort of COVID-19 patients was caused by the immune system failing to switch off once the COVID-19 infection wanes, leading to airway inflammation and injury.

While previous studies have examined the causes of post-COVID-19 breathlessness by looking at blood biomarkers, this latest study looked directly at which immune cells are active in the lungs.

The researchers studied scans of the lungs and how well they were functioning, as well as analysing fluid from within the lungs and blood samples, to assess the presence of nearly 500 proteins.

The study included 38 post-COVID-19 patients three to six months after they left hospital and 29 healthy volunteers, who had no underlying diseases and had not had COVID-19.

At three to six months, there were more immune cells in the lungs of the post-COVID-19 participants than in the healthy controls, but there was no difference in the immune cells seen in the blood of the post-COVID-19 patients and the healthy participants.

The finding that the immune response in the blood does not seem to match that of the lungs emphasises the importance of assessing airway immunity in order to better understand persistent respiratory symptoms post COVID-19, the researchers say.

The participants in the study contracted COVID-19 before vaccines were available.

Pandemic wipes out one third of UK cancer research

There was a substantial decrease in the number of cancer research projects getting off the ground in the UK between 2019 and 2020, with the lifetime value of the projects funded in 2020 falling 57%, to £1.29 billion, compared to pre-pandemic 2019 when £3.03 billion was committed.

The new figures are from the UK National Cancer Research Institute, which has been collecting data on cancer research funding since 2002.

NCRI is concerned that as a result, the amount spent on cancer research will continue to decline over the next five years.

In the financial year 2020/21, funding agencies that are members of NCRI spent a total of £634 million on cancer research, a decrease of 9% compared to 2019/20. For the five years before the COVID-19 pandemic, there was an upward trend in cancer research spending.

In particular, the pandemic has hit charities like Cancer Research UK, which rely on High Street shops and events such as coffee mornings and sponsored runs to raise much of their revenue. Charity funding bodies have done everything possible to ensure that funding commitments made before the pandemic were honoured, but this has meant less money for new research.

While a 9% decrease in the amount spent on cancer research is alarming, there is concern this does not reflect the full impact of the COVID-19 pandemic, said Iain Frame, CEO of NCRI. “This is because several NCRI partners made tough decisions during the COVID-19 pandemic to maintain their research funding commitments, including moving priorities away from other areas and making redundancies,” he said.

There has been a substantial decrease in the number and lifetime value of new cancer research projects funded, and as current projects come to an end, there could be a continued decrease in spending on cancer research over the coming years.

New human genetic variants found to be associated with becoming critically ill with COVID-19

More than 20 human genetic variants that predispose patients who are infected with SARS-CoV-2 to become critically ill have been uncovered by the UK Genomicc (Genetics Of Mortality In Critical Care) project.

The findings may have direct implications for the development of new treatments and the future prioritisation of therapy.

Critical illness in COVID-19 is caused by inflammatory lung injury, which is mediated by the host’s immune system. Genetic factors are known to have a role.

In the study, the researchers compared whole genome sequences of more than 7,000 patients who became critically ill with COVID-19, with those of more than 48,000 matched control individuals.

They found 23 variants that predispose to life-threatening disease, 16 of which were previously unknown. They include variants within genes involved in interferon signalling, leukocyte differentiation and the production of mucin proteins, all of which are important factors in the regulation of the immune system and functioning of the lungs.

Some of the variants identified are potential drug targets, raising the possibility of new therapies aimed at genetic mechanisms that predispose to life-threatening disease.

The results, published in Nature, are also broadly consistent with the multicomponent model of COVID-19, which holds at least two distinct components can predispose to life-threatening illness: a failure to control viral replication and an enhanced tendency towards lung inflammation and blood clotting.

UK Biobank study reveals changes in the brain after COVID-19

New research has found there are changes to the human brain, including in areas associated with smell and memory, following SARS-CoV-2 infection.

The findings reveal damaging effects of COVID-19 and also increase understanding of how the disease spreads through the central nervous system.

Whether these effects persist in the long term, or can be partially reversed, requires further investigation.

Although there was some evidence to suggest COVID-19 may cause brain-related abnormalities, most studies have focused on hospitalised patients with severe disease, and have been limited to imaging patients after they had the infection.

The effects of SARS-CoV-2 on the brain in milder and far more common cases remain unknown,

To investigate this, the researchers looked for changes in the brains of 785 UK Biobank participants, aged 51–81. They had had two brain scans, on average 38 months apart, and had completed cognitive tests.

A total of 401 participants tested positive for infection with SARS-CoV-2 between their two scans, of whom 15 were hospitalised; the remaining 384 individuals were age- and sex-matched controls.

There was an average of 141 days between participants receiving a COVID diagnosis and the second imaging scan. The researchers identified various long-term effects following infection, including a greater reduction in grey matter thickness in the orbitofrontal cortex and parahippocampal gyrus, regions that are associated with smell and memory of events.

In addition, participants who had COVID-19 displayed evidence of tissue damage in regions associated with the olfactory cortex, which is an area of the brain linked to smell, and an average reduction in whole brain sizes.

On average, the participants who were infected with SARS-CoV-2 also showed greater cognitive decline between their two scans. This was associated with the atrophy of the cerebellum, which is linked to cognition.

The researchers also performed a control analysis on people who developed pneumonia that was not related to COVID-19, enabling them to show that the changes were specific to COVID-19, and not due to generic effects of contracting a respiratory illness.

New research suggests a causal link between blood group and severe COVID-19

A new study has analysed over 3,000 proteins to identify those which are causally linked to the development of severe COVID-19. The researchers found six proteins that could underlie an increased risk of severe COVID-19 and eight that could contribute to protection from severe COVID-19.

The findings provide insight into potential new targets for approaches to treat and prevent severe COVID-19.

One of the proteins, ABO, which was identified as having a causal connection to the risk of developing severe COVID-19, determines blood groups. The researchers say that suggests blood groups play an instrumental role in whether people develop severe forms of the disease.

Researcher Alish Palmos from Institute of Psychiatry, Psychology & Neuroscience, King’s College London said, “We have used a purely genetic approach to investigate a large number of blood proteins and established that a handful have causal links to the development of severe COVID-19. Honing in on this group of proteins is a vital first step in discovering potentially valuable targets for development of new treatments.”

The study considered two incremental levels of severity of COVID-19: hospitalisation and respiratory support or death. Using data from a number of genome-wide association studies the researchers found the six proteins that were causally linked to an increased risk of hospitalisation or respiratory support/death due to COVID-19 and the eight that were causally linked to protection against severe disease.

ABO was causally associated with both an increased risk of hospitalisation and a requirement for respiratory support. This supports previous findings around the association of blood group with higher likelihood of death. Taken together with previous research showing that the proportion of blood group A is higher in COVID-19 positive individuals, this suggests blood group A is a candidate for follow-up studies.

Gerome Breen, professor of genetics at King’s College said, “What we have done in our study is provide a shortlist for the next stage of research. Out of 1,000s of blood proteins we have whittled it down to about 14 that have some form of causal connection to the risk of severe COVID-19.”

People spreading misinformation about COVID-19 met with ridicule not facts

A study analysing the spread and refutation of misinformation about facemasks on Twitter during the Covid-19 pandemic shows that rather than trying to provide the correct information, people were made fun of for their ignorance.

From a democratic debate perspective, the results are not encouraging, said Rebecca Adler-Nissen, one of the five researchers at the University of Copenhagen and Aarhus University, who carried out the research.

“We tend to believe that people eager to correct misinformation will be very fact-oriented. But our study shows that this group of people typically choose to ridicule those spreading misinformation,” Adler-Nissen said. “Instead of bridging gaps or inviting people to change their minds by updating their knowledge, their response to misinformation takes the form of know-it-all remarks intended to patronise their opponent and praise themselves.”

The researchers analysed 9,345 Danish-language tweets about facemasks and COVID-19 posted between February and November 2020.

The analysis shows that only around 5% (471 tweets) focus on misinformation. Of these, around 3% of all tweets and retweets disseminated misinformation about facemasks, for example claiming facemasks are dangerous because they raise the user’s CO2 levels, or that facemasks are irrelevant because COVID-19 is pure fabrication.

For only 2% of the 471 incorrect tweets was there any attempt to correct the misinformation. In most cases the response was rather to deride, ridicule or stigmatise the sender of the misinformation, often using humour: 33% of all tweets rejecting misinformation used satire, irony and humour.

The researchers conclude that a lot of the people who either spread or reject misinformation are really trying to do the same thing: namely defend their own social position among like-minded people.

The study is part of the interdisciplinary HOPE project, which with support from the Carlsberg Foundation is examining how democracies have coped with the COVID-19 pandemic.

The study calls into question our ability as citizens to discuss and correct misinformation in social media, when those who should know better often choose to ridicule rather than to inform, the researchers say.

“Twitter in the US has experimented with tasking volunteers with checking assertions. Our analysis suggests that this is a complex task, because people do not go online simply to exchange information, but also to consolidate their own status and identity,” Adler-Nissen said. “When people commit to fighting misinformation, it is also a way to make themselves visible to like-minded people. And we need to be aware of that dynamic.”

RNA interference could be new approach to treating COVID-19

A team led by the Technical University of Munich (TUM) has successfully used a specific enzyme to destroy the genetic information of SARS-CoV-2 directly after the virus penetrates human cells. The researchers say this could provide the basis of a therapy to treat COVID-19.

The approach depends on harnessing RNA-Induced Silencing Complex (RISC), an enzyme which cuts viral RNA.

Efforts have been made for quite some time now to make therapeutic use of this mechanism. The researchers set out to discover how viral RNA can be best attacked using RISC, and at which stage of the replication cycle treatment should take place.

They found that RISC is most effective when the virus has just penetrated a human cell.

The researchers tested their approach in human lung tissue, confirming the results and are now planning to develop a method for delivering the enzyme directly to the lungs in an inhaled formulation.

New method for measuring spread of COVID-19 from blood donations

Researchers at Aston University in the UK have helped develop a mathematical model which can estimate daily transmission rates of COVID-19 and other infections by testing for antibodies in blood collected at blood donation centres.

They say it is a faster way to assess transmission than existing epidemiological models, and can be used to assess infection rates in the absence of population level testing for COVID-19 infections.

The Aston researchers worked with counterparts at the Universidade Federal de Minas Gerais in Brazil to apply their models to results obtained from Brazilian blood donor centres. The testing was done by Fundacao Hemominas, one of the largest blood services in Brazil, which covers an area similar to that of continental France.

They used the reported number of SARS-CoV-2 cases along with data on anti-SARS-CoV-2 antibodies in blood donors, to determine daily transmission rates and cumulative incidence rate of reported and unreported cases.

The model gave the experts the ability to have higher level view of infection rates and the relative rate of immunity, compared to official measurements.

The antibody testing started at the beginning of the pandemic and involved 7,837 blood donors in seven cities during March–December 2020. At that point COVID-19 diagnostic testing wasn’t widely available and there was a high proportion of undetected asymptomatic or light symptomatic cases. The data obtained allowed the experts to estimate the proportion of people who were going undiagnosed.

“Public communication about the COVID-19 epidemic was based on officially reported cases in the community, which strongly underestimates the actual spread of the disease in the absence of widespread testing,” said Felipe Campelo, senior lecturer in computer science at Aston University. “This difference underscores the convenience of using a model-based approach such as the one we proposed, because it enables the use of measured data for estimating variables, such as the total number of infected persons.”

The model delivers daily estimates of relevant variables that usually stay hidden, including the transmission rate and the cumulative number of reported and unreported cases of infection, Campelo said.

From July 2020 there was a sharp increase in the number of people tested for COVID-19 in Brazil, as new infrastructure became available. This allowed the experts to further validate their methodology by observing how officially recorded data became closer to the model predictions once testing became more widespread, including for asymptomatic or mildly symptomatic people.

In future, the researchers aim to improve the accuracy of the model by introducing changes to account for vaccination effects, waning immunity and the potential emergence of new variants.

New research shows face masks play a crucial role in preventing spread of COVID-19

An international research team has developed a new theoretical model to better assess the risks of spreading viruses such as COVID-19, with and without a face mask.

The results show the standard ‘safe’ distance of two metres does not always apply, and in fact varies greatly depending on a range of environmental factors, and that face masks can indeed play a crucial role.

Modelling the direct virus exposure risk associated with talking, coughing and sneezing, the research shows it is possible to calculate the direct risk of spreading COVID-19 infection, by including factors such as interpersonal distance, temperature, humidity levels and viral load, and to demonstrate how these risks change with and without a face mask.

For example, a person talking without a face mask can spread infected droplets one metre away. Should the same person cough, the drops can be spread up to three metres, and if the person sneezes, the spread distance can be up to seven metres.

But using a face mask, the risk of spreading infection decreases significantly. Provided the face mask is worn correctly, the risk of infection is negligible even at distances as short as one metre, regardless of environmental conditions, and if an infected person is talking, coughing or sneezing.

The model uses data from recent experiments on droplet emissions, enabling the researchers to take several factors into account and quantify the risk of infection, with and without a face mask.

The study was led by the University of Padua, in collaboration with the University of Udine, the University of Vienna and Chalmers University of Technology.

European Medicines Agency takes on new pandemic-driven oversight role

The regulation reinforcing EMA’s role in crisis preparedness and management of drug and medical device supplies has come into force today, putting some of the structures and processes established by EMA during the COVID-19 pandemic on a more permanent footing.

EMA is now responsible for monitoring drug supplies and reporting shortages of critical drugs during a crisis. From 2 February 2023, it will have a similar role in medical devices.

To ensure a robust response to serious shortages, a Medicines Shortages Steering Group, will be set up.

In addition, a standing Emergency Task Force will provide scientific advice on the development of products intended for use during a public health emergency; review scientific data; provide recommendations on the use of drugs that do not have formal regulatory approval; and coordinate independent vaccine effectiveness and safety monitoring studies.

The composition and rules under which the medicines shortages group and the emergency task force operate are due to be endorsed by EMA’s management board in March.

A further preparedness measure will involve updating the role of the EU Single Point of Contact (SPOC) network, the system that EMA and national regulators use to exchange information on shortages.

Under the new mandate, SPOC will make recommendations on all matters relating to monitoring and management of shortages and availability issues during a crisis, and provide guidance to companies.

Transmission game tests in advance how effective pandemic control measures will be

Researchers at the Max Planck Institute for Human Development, Germany, with collaborators at the Plymouth University, UK, and the IESE Business School, Spain have developed a game they say can test in advance the effectiveness of control measures to slow the spread of SARS-CoV-2.

The study found the most effective approach was a message that directly appealed to the public, contained moral reason, and was clear and consistent.

The research, published in Science Advances, involved seven groups of 100 people from a cross section of the US population playing a game designed to emulate virus transmission. It integrated simulations of outbreak dynamics with monetary stakes for the players.

Blue players represented healthy individuals, and purple players infected individuals. The aim of the game was to stay blue.

If players took more risks and managed to stay blue, they got a higher reward. However, if they got ‘infected’ and turned purple, they lost everything.

The interventions in the game implemented principles used by countries worldwide to persuade people to comply with pandemic control measures.

The study showed that the most effective way to reduce risk-taking behaviour was a message with a simple imperative backed by a moral explanation, for example, ‘choose this action to protect your and other players’ money’. On average, participants who responded to these instructions also earned the highest amount of money.

Showing the case rate numbers, that is how many players were purple, had no effect on behaviours, nor did saying how many participants were choosing less risky behaviours. That actually led to a slight increase in risk-taking behaviour overall.

“Non-pharmaceutical interventions, such as wearing masks, maintaining physical distance, and reducing contacts, require large-scale behaviour change, which depends on individual compliance and cooperation,” said lead author Jan Woike, lecturer in psychology at Plymouth University. “The behavioural sciences offer cognitive and communication tools to help, but the effectiveness of methods to increase compliance has rarely been tested in controlled scenarios that reflect the dynamics of infectious outbreaks.”

What is important about the transmission game is that it makes it possible to test the effectiveness of an intervention before implementing it in a real pandemic.

“It was interesting to note that the most effective intervention was not the one that participants liked the most. Clear and consistent messaging worked best in reducing risk-taking behaviours,” Woike said.

Anglo-German research team uses synthetic biology to uncover secrets of SARS-CoV-2 spike protein

Scientists at the Max Planck Institute for Medical Research in Heidelberg and their collaborators at the Max Planck Centre for Minimal Biology at Bristol University have developed a new approach to studying SARS-CoV-2, after creating a stripped down version of the virus, or virion, to which they can now attach distinct structures, such as the spike protein by which the virus enters human cells.

This has enabled them to study individual molecular mechanisms in a controlled setting, which they can further manipulate and tune.

Using this technique to study the spike protein they have discovered a switching mechanism, showing that upon binding of inflammatory fatty acids, the spike protein changes its conformation, thereby becoming less visible to the host immune system.

The synthetic construct also overcomes safety concerns about handling live virus because the virions have a similar structure to natural viruses but do not contain any genetic information.

“Even more important for us, as we build these synthetic virions from scratch, is that we can precisely design their composition and structure. This allows us to perform a very systematic, step-by-step study on distinct mechanisms”, said Oskar Staufer, first author of the paper describing the research.

The inflammatory fatty acids that are released during any inflammation in the body help spark the immune response and healing processes. While it was known that the spike protein has a distinct region where inflammatory fatty acids can bind, the function of this binding pocket was previously not understood.

Using the virions, the researchers were able to show that upon binding of a fatty acid, the spike protein changes its conformation and folds, becoming less visible to the immune system. As a result, fewer antibodies bind to the spike protein. Following on from this discovery, the researchers are now assessing if it can inform the development of antiviral therapies.

Late to the party, GSK and Sanofi ready to apply for approval of COVID-19 vaccine

Sanofi and GlaxoSmithKline have announced they are now ready to submit the file for approval of their jointly developed COVID-19 vaccine, after reporting positive results in phase III efficacy trials and of its use as a booster.

The data show the vaccine induced robust immune responses and had a favourable safety profile in multiple settings. In participants who had received two doses of an mRNA or adenovirus vaccine, the Sanofi-GSK booster vaccine induced a significant increase in neutralising antibodies across different vaccines and age groups.

When the Sanofi-GSK vaccine was used as a two-dose primary series followed by a booster dose, neutralising antibodies also increased significantly.

“The Sanofi-GSK vaccine demonstrates a universal ability to boost all platforms and across all ages. We also observed robust efficacy of the vaccine as a primary series in today’s challenging epidemiological environment,” said Thomas Triomphe executive vice president, Sanofi Vaccines. “No other global phase III efficacy study has been undertaken during this period with so many variants of concern, including Omicron.”

The companies are now in discussions with regulators, including the US FDA and European Medicines Agency.

New research shows two doses of COVID-19 vaccine or natural infection provide limited protection against Omicron variant

Scientists at the Medical University of Vienna have published data showing people who are dual vaccinated or have recovered from a natural COVID-19 infection have virtually no protection against the currently circulating Omicron variant of SARS-CoV-2.

The research indicates only individuals who have received a third booster dose of vaccine generate antibodies that can partially block Omicron.

In a study led by Rudolf Valenta at the Institute of Pathophysiology and Allergy Research, an Austrian subpopulation of vaccinated and recovered individuals was examined for antibody status and protection against the Wuhan, Delta and Omicron variants of SARS-CoV-2. The researchers tested whether the virus can bind to the ACE2 receptor on human cells via its receptor binding domain (RBD) in people immunised with all vaccines and vaccine combinations currently licensed in Austria.

The results showed that both COVID-19 convalescent individuals and individuals who had been vaccinated twice, had developed antibody protection against Delta. However, the antibodies were not able to block binding of the RBD of Omicron.

Blockade of Omicron was better in those individuals who had received a third vaccination. "The third vaccination developed protective antibodies in many individuals," said Valenta. “However, there is also a significant proportion (20%) in whom no protection was established.”

The RBD in variants that emerged before Omicron differed only slightly from one to the other, so that infections with these variants and immunisation with the currently available vaccines provided protection. Omicron is the first variant that differs greatly from the previous variants in its RBD, consequently infection with earlier variants, and currently available vaccines, provide little or no protection against it.

Why natural killer cells react to COVID-19

Little has been known to date about how the immune system’s natural killer (NK) cells detect which cells have been infected with SARS-CoV-2. Now an international team led by researchers from Karolinska Institutet have shown that NK cells respond to a particular peptide on the surface of infected cells.

The study, which is published in Cell Reports, is an important piece of the puzzle in understanding how the immune system reacts to COVID-19.

Unlike antibodies, NK cells are able to recognise and kill virus-infected cells immediately, without having encountered them before. This ability is controlled by a balance between activating and inhibiting receptors on NK cells, which can react to different molecules on the surface of other cells.

The research shows cells infected with SARS-CoV-2 carry on their surface a peptide from the virus that triggers a reaction in NK cells carrying a receptor, NKG2A, which is able to detect the viral peptide.

The study involved collaboration between the Karolinska and laboratories and universities in Italy, Germany, Norway and the US. In the first phase, the researchers used computer simulations that were then confirmed in the lab by infecting human lung cells with SARS-CoV-2 in a controlled environment. That made it possible to demonstrate that NK cells with the NKG2A receptor are activated to a greater degree than the NK cells without it.

The study is now being followed up using a biobank at the Karolinska containing blood samples from over 300 people treated for COVID-19 during the first wave of the pandemic, to assess if the composition of NK cells in a given patient contributed to how severe their symptoms were when infected with SARS-CoV-2.

New optical method for rapid detection of COVID-19

Researchers at the University of Seville have devised a new highly accurate optical method for detecting SARS-CoV-2 in saliva from COVID-19 patients.

It has also been possible to detect SARS-CoV-2 in saliva of asymptomatic people. The main advantage of the new technology over PCR is in the speed of sample processing and the ability of the optical system to simultaneously analyse a large number of samples.

The researchers have demonstrated proof of concept in the lab and are currently working on validating the new methodology, which detects virus with high sensitivity imaging and data processing based on advanced statistics and artificial intelligence.

Multiple samples can be processed simultaneously, without contact or reagents and with relatively simple equipment that requires minimal training to operate.

Details of the proof of concept study were published in Nature Scientific Research earlier this month.

Institut Pasteur scientists find bats carry viruses genetically similar to SARS-CoV-2

Despite all the controversy - and the accusation that SARS-CoV-2 escaped from the Wuhan Institute of Virology - the origin of the virus and how it was transferred into the human population remains unknown.

Now, scientists at Institut Pasteur have identified coronaviruses that are genetically similar to SARS-CoV-2, within bat populations in northern Laos. Their research, published as an accelerated preview in Nature suggests that these novel bat coronaviruses may have the potential for infecting humans.

Lead author Marc Eloit and colleagues tested 645 bats, belonging to 6 families and 46 species, living in limestone caves in northern Laos.

They found three viruses that they considered to be closely related to SARS-CoV-2, with the genetic sequences encoding the ACE2 binding regions by which SARS-CoV-2 enters human host cells similar to that of SARS-CoV-2.

These bat viruses were able to bind to human ACE2 receptors more efficiently than the original Wuhan SARS-CoV-2 strain isolated from humans. One of these viruses was also shown to replicate within human cell lines, but was inhibited by antibodies that neutralise SARS-CoV-2.

The findings support the hypothesis that SARS-CoV-2 could have originated from bats living in the limestone caves of Southeast Asia and southern China.

This is the first time that SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through the ACE2 pathway have been identified. The ACE2 receptor binding domains of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2.

“Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses potentially infectious for humans circulate in [bats] in the Indochinese peninsula,” the researchers conclude.

Italian study confirms the extent of the ‘Covidisation’ of biomedical research

Among the casualties of the COVID-19 pandemic, one that has not been highlighted to date is biomedical research not directly related to the pandemic and SARS-CoV-2.

The extent of the impact on other fields of research is seen in a new analysis carried out by researchers at the IMT School for Advanced Studies in Lucca, Italy. They looked at papers that appeared on the PubMed search engine for published research between the beginning of 2018 and the end of 2020, showing that COVID-19 profoundly affected and shifted priorities in the biomedical field.

While publications related to all the aspects of the pandemic skyrocketed, publications, clinical trials, and grants in subjects not directly related to COVID-19 decreased by up to 25% compared to the pre-COVID era, a phenomenon referred to as the ‘Covidisation’ of research.

To conduct their analysis, Massimo Riccaboni, professor of economics at the IMT School, and Luca Verginer, now a post-doc at the ETH Zürich, analysed more than 34 million biomedical citations on PubMed, developing an index of keywords related to COVID-19. One example is anosmia, loss of the sense of smell, which quickly emerged as a major symptom of infection.

In the first three months of the pandemic, the number of scientific papers about COVID-19 was five times higher than the number of articles on H1N1 swine influenza. The term betacoronavirus skyrocketed from 2019 to 2020, while alphacoronavirus - a different genus from SARS-CoV-2 - did not experience any growth.

Medical terms not related to COVID-19 appeared less and less frequently in the scientific literature, with a fall of between 10 – 13% in the number of papers, and in their impact factor of almost 20%.

Another effect emerged from the analysis, with grants assigned in the 2018 pre-COVID era, diverted to support COVID-19 related research, as seen from the number of publications linked to those grants.

The Italian researchers did not coin the term ‘Covidisation’ of research, but their analysis reveals the magnitude and proportions of this shift for the first time. “The overall picture that emerges is that there has been a profound realignment of priorities and research efforts, with the entirety of medicine focused on COVID-19,” said Riccaboni.

“While this effort and the mobilisation of the scientific community brought us vaccines, this shift in fact also displaced biomedical research in the fields not related to COVID-19, bringing other undesired consequences,” he said.

This phenomenon adds to other negative impacts of COVID-19 on research, such as the record number of studies suspended, the toll on women and early-career scientists, and the questionable quality of methods and data gathered in fast-tracked, small scale clinical trials.

Spanish researchers point to vagus nerve dysfunction as possible cause of long COVID

A pilot study suggests that many of the symptoms connected to long COVID could be linked to the effect of the virus on the vagus nerve.

One of the most important multi-functional nerves in the body, the vagus nerve extends from the brain to the torso and into the heart, lungs and intestines, as well as several muscles, including those involved in swallowing.

It is responsible for a wide variety of functions including controlling heart rate, speech, the gag reflex, moving food through the intestines, sweating, and many others.

The researchers propose SARS-CoV-2-mediated vagus nerve dysfunction could explain long COVID symptoms, including dysphonia (persistent voice problems), dysphagia (difficulty in swallowing), dizziness, tachycardia (abnormally high heart rate), low blood pressure and diarrhoea.

This is based on morphological and functional evaluation of the vagus nerve in cohort of long COVID patients with symptoms that are known to be related to its dysfunction.

In 22 patients in the study, the most frequent vagus nerve damage-related symptoms were diarrhoea, tachycardia, dizziness, dysphagia, dysphonia, and low blood pressure. Almost all had at least three vagus nerve dysfunction-related symptoms.

In this pilot evaluation, most long COVID subjects with vagus nerve dysfunction symptoms had a range of significant, clinically-relevant, structural and/or functional alterations in their vagus nerve, including nerve thickening, trouble swallowing, and symptoms of impaired breathing, the researchers said. “Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”

SARS-CoV-2 variants have potential to escape the cellular immune response

A number of existing strains of SARS-CoV-2, and possible future variants that could arise, have the potential to escape the immune system’s cytotoxic T cell response in some of the population, according to a computational modelling study conducted by Antonio Martín-Galiano and colleagues at the Carlos III Health Institute in Madrid.

The T cell response is encoded by HLA (human leukocyte antigen) genes which show the greatest diversity of any genes in humans. As a result, different individuals have different HLAs that lock onto SARS-CoV-2 based on the motifs of different epitopes on the surface of the virus.

The thousands of different HLA types in the human population and the thousands of epitopes on SARS-CoV-2, make it difficult to directly evaluate the immune response of every human HLA to every viral variant by in vitro screening.

Instead, using bioinformatics techniques, the researchers first determined the full set of epitopes from the original reference strain of SARS-CoV-2 from Wuhan, China.

They found 1,222 epitopes of SARS-CoV-2 were associated with the 12 major HLA subtypes that cover around 90% of the human population. That means at least 9 out of every 10 people can launch a T cell response to COVID-19 based on these 1,222 epitopes.

However, SARS-CoV-2 has gathered thousands of mutations since it was first characterized late in 2019. The researchers computationally analysed whether any of almost 118,000 different SARS-CoV-2 isolates from around the world had mutations in the epitopes seen on the Wuhan strain. They showed 47% of the epitopes were mutated in at least one isolate.

In some cases, existing virus isolates had mutations in multiple epitope regions. However, these cumulative mutations never affected more than 15% of epitopes for any given HLA type.

The distribution of different HLA types varies by geography and when susceptible HLAs were cross-referenced with the geographic origin of their respective escape isolates, it was shown they co-existed in some geographical regions, including sub-Saharan Africa and East and Southeast Asia. That suggests there is potential genetic pressure on the T cell response in these areas.

“The accumulation of these changes in independent isolates is still too low to threaten the global human population,” the researchers said. But they added, “Our protocol has identified mutations that may be relevant for specific populations and warrant deeper surveillance.”

In addition, Martín-Galiano notes that “unnoticed SARS-CoV-2 mutations” might in future “threaten the cytotoxic T response” in some populations.

Researchers show host-induced mutations in SARS-CoV-2 limit its ability to replicate

In the popular understanding, mutations of the SARS-CoV-2 virus are associated with the emergence of virus variants that are more contagious and pathogenic than their predecessors.

However, a new study shows that virus mutations often work in the opposite direction.

Virology researchers at the University of Gothenburg’s Sahlgrenska Academy have mapped mutation patterns in the SARS-CoV-2 and shown that a naturally occurring human enzyme ADAR1 (adenosine deaminases acting on RNA), can cause mutations that impairs the virus’ ability to replicate.

ADAR1 in the membrane of human cells can induce mutations in nucleotides that form the building blocks in the RNA of the virus.

“Our study shows that there is an inverse relationship between the viral load and the extent to which ADAR1 has mutated the virus. We also found that ADAR1-induced mutations are the most common type of SARS-CoV-2 mutation,” said virologist Johan Ringlander.

In particular, the scientists noted that individual patients are often infected with more than one variant of the virus. When mutations in relatively rare virus variants were investigated, it was found that a common mutation induced by ADAR1, in which one nucleotide, guanosine, replaces another, adenosine, significantly worsened the reproductive ability of SARS-CoV-2.

Analyses of more than 200,000 virus strains from patients who were ill with COVID-19 showed that mutations caused by ADAR1 were mainly circulating in summer 2020, when transmission and mortality rates were low in Europe. When transmission and mortality rates were higher, virus variants with ADAR1-induced mutations were uncommon, probably because they were outcompeted by more infectious virus strains.

The results clarify how human host cells can generate mutated virus variants. “Mutations can make a virus more infectious, but in most cases the mutations we’ve studied make the virus weaker; instead of spreading, it’s removed from infected cells. These findings suggest that ADAR1 serves as a protective mechanism used by the body to limit viral infections,” Ringlander said.

“When SARS-CoV-2 multiplies in the airways, inflammation occurs. Its effects include activation of ADAR1, which in turn reduces the likelihood of the virus infecting other cells, said lead author Michael Kann, professor of clinical virology at Sahlgrenska Academy. “We’re currently investigating whether this protective mechanism may be important in other viral infections as well,” Kann said.

Long-COVID in children defined

The first research definition of what is meant by Long-COVID in children and young people has been formally agreed, following a UK government-funded study to map the symptoms.

The definition sets out what should be measured; the next stage of the research project is to reach consensus on how to make these measurements.

The definition will be important in providing an internationally agreed standard that can be used to measure outcomes in clinical trials of potential treatments. Currently, the lack of such agreement means that data collection is inconsistent, making it hard to assess efficacy.

The definition in children and teenagers closely complements that proposed by the World Health Organisation for Long COVID in adults, and if widely adopted, will substantially help strengthen the evidence base on this debilitating condition, say the researchers.

The slew of definitions currently used, all of which differ in number, type, and duration of symptoms has contributed to the very wide reported variations in the estimated prevalence of Long COVID in children of 1% to 51%.

A consistently applied definition of Long COVID will enable researchers to reliably compare and evaluate studies on prevalence, disease course, and outcomes, providing a more accurate picture on the true impact of the condition.

Consensus was reached among a representative panel of 120 international experts skilled in health service delivery (47), research (50), and lived experience (23).

The research definition of Long COVID in children and young people is as follows:

A condition in which a child or young person has symptoms (at least one of which is a physical symptom) that:
Have continued or developed after a diagnosis of COVID-19 (confirmed with one or more positive COVID tests)
Impact their physical, mental or social wellbeing
Are interfering with some aspect of daily living (eg, school, work, home or relationships) and
Persist for a minimum duration of 12 weeks after initial testing for COVID-19 (even if symptoms have waxed and waned over that period)

These translate into, “Post-COVID-19 condition occurs in young people with a history of confirmed SARS CoV-2 infection, with at least one persisting physical symptom for a minimum duration of 12 weeks after initial testing that cannot be explained by an alternative diagnosis. The symptoms have an impact on everyday functioning, may continue or develop after COVID-19 infection, and may fluctuate or relapse over time.”

The study has been accepted by the journal Archives of Disease in Childhood, but is yet to be published.

Longitudinal study shows three exposures to viral spike protein protects against Omicron variant

Scientists at Ludwig-Maximilians-Universitaet in Munich, Helmholtz Munich, and Technical University of Munich have shown that the immune system is capable of neutralising the Omicron variant of SARS-CoV-2 after three exposures to the spike protein of the virus.

In a paper in Nature Medicine, they show this level of exposure leads to production of a high quantity of high quality neutralising antibodies that have high affinity for the spike protein.

This was the case in people who had received three doses of vaccine, people who had recovered from COVID-19 and then had two vaccinations, and to double-vaccinated people who then had a breakthrough infection.

The longitudinal study involved 171 participants who are members of staff at the University Hospital, who have been regularly tested for COVID-19. The researchers identified individuals who had contracted SARS-CoV-2 during the first wave of the pandemic in spring 2020, and compared them to a second group of people who had not been infected. Subsequently, both groups were vaccinated and monitored for almost two years. The cohort included 98 people who had a natural infection and 73 who had not.

The longitudinal study made it possible to follow how the immune response evolves over time against the virus and after vaccination. It was shown that the ability of the immune system to neutralise the virus correlates only weakly with the amount of neutralising antibodies. Rather, the critical factor was how effectively these antibodies bind to the virus and block infection.

Omicron exhibited the most pronounced evasion from neutralising antibodies compared to all other viral variants tested and three separate exposures to the spike protein are needed to build up high-level neutralising activity against this newest variant of concern.

Severe COVID-19 linked to damage to blood vessels

SARS-CoV-2 infection has little effect on some people, while others develop life-threatening COVID-19 symptoms. But although it is known that severe disease is marked by strong activation of the immune system, it is not known exactly why symptoms and disease severity vary so significantly.

A team of German scientists has now discovered that a hallmark of severe COVID-19 is damage to the endothelial cells that line the blood vessels.

By studying 25 patients with severe COVID-19 and 17 recovered patients in the intensive care unit, the scientists were able to prove that the severity of disease is linked to disruption of the endothelial barrier and to identify seven proteins in blood that are biomarkers of a severe form of COVID-19.

They also showed that recovery was dependent on the regeneration of damaged endothelial cells.

In addition to enabling patients to be triaged according to their risk of severe disease, the biomarkers are potential targets for COVID-19 therapies.

The team now wants to investigate which elements of the immune system lead to damage to the endothelium and if there are indicators of which patients will suffer from Long-COVID.

Population based study in Sweden shows vaccines continue to protect against severe COVID-19 over time

The level of protection COVID-19 vaccines provide against infection quickly wanes, though they continue to protect against severe disease, according to a nationwide, registry-based study performed by researchers at Umeå University, Sweden, published in The Lancet.

“The bad news is that the protection against infection seems to be diminished by seven months after the second dose of vaccine,” says Peter Nordström, professor of geriatric medicine at Umeå University. “The good news, however, is that the protection against a severe infection that leads to hospitalisation or death seems to be better maintained.”

The study included almost 1.7 million individuals, with the results then confirmed in an even larger population of almost 4 million individuals. It showed protection against infection of any severity waned progressively following the peak of protection, which occurred a month after the second dose.

Protection against severe disease was 89% after one month and 64% from four months and onwards during follow-up of nine months. There was some evidence to suggest a lower level of protection in the oldest individuals.

Anna Nordström, adjunct professor in public health at Umeå University and co-author of the study said a key strength of the study is the long follow-up and it was done in a real-world setting based on the total population of Sweden. “This increases the possibility to generalise the results to other countries with similar population structure as in Sweden,” she said.

Human challenge studies of SARS-CoV-2 are safe

The world’s first human challenge study in which healthy volunteers were deliberately infected with the SARS-CoV-2 virus in controlled conditions has shown this is safe.

That sets the scene for other human challenge studies to be used in efficacy studies of vaccines, antiviral drugs and diagnostics, according Open Orphan, the Dublin-based contract research organisation that ran the trial.

The aim was to find the lowest dose of nasally administered SARS-CoV-2 that reliably caused a low level infection, enabling the testing of drugs and vaccines.

Among the 18 of 34 volunteers who contracted COVID-19, there were no serious symptoms. Sixteen of the 18 had mild cold like symptoms, while the other 16 volunteers did not become infected.

The data supports the safety of the infection challenge model for assessing vaccines and therapies, Open Orphan said. Similar challenge studies are routinely used in testing treatments for other respiratory diseases, including flu and respiratory syncytial virus infections.

The human challenge study was funded by the UK government and carried out at the Royal Free Hospital in London. The research is continuing, to adapt the model for emerging variants of SARS-CoV-2 and to reflect the fact that unlike the volunteers in this first study, most of the UK population has now been vaccinated or had a natural infection.

Andrew Catchpole, chief scientist at hVivo, the unit of Open Orphan that oversaw the study, and co-investigator on the trial said, “Importantly the study demonstrated that SARS-CoV-2 challenge studies are safe and well tolerated by the volunteers with no serious symptoms and no serious adverse events.”

While the study used the original SARS-CoV-2 strain, and there are differences in transmissibility between it and the other variants, the same factors will be responsible for protection against it, meaning the findings remain valuable for variants such as Delta or Omicron, Catchpole said. “These data provide a clear platform to now utilise the human challenge model to expedite product efficacy testing for new vaccines or antivirals.”

Smart FFP2 facemask sends a mobile alert when CO2 limits are exceeded

Scientists and engineers at the University of Granada have developed and tested a ‘smart’ FFP2 facemask that notifies the user via their smartphone when the permitted carbon dioxide limits inside the mask are exceeded.

This addresses a problem that has been particularly highlighted since the COVID-19 pandemic began, of re-inhaling previously exhaled CO2 trapped inside facemasks.

Wearing FFP2-type facemasks for any length of time produces a concentration of CO2 between the face and the mask that is higher than the normal atmospheric concentration. CO2 rebreathing can cause adverse effects, even in healthy people, such as general malaise, headaches, fatigue, shortness of breath, dizziness, sweating, increased heart rate, muscle weakness, and drowsiness.

These negative effects are known to be linked to both the duration of exposure and the concentration of the gas. Some health regulations recommend a maximum value of 0.5% CO2 in the working environment (averaged over an 8-hour day), or that a 30 minute exposure to 4% CO2 be considered very harmful to health.

“Notwithstanding the generalised evidence in favour of facemasks to reduce transmission throughout the population, there is also broad agreement on the possible adverse effects caused by their prolonged use, mainly as a consequence of the increase in respiratory resistance and the re-inhalation of the CO2 that accumulates inside the mask,” the researchers say.

The new FFP2 facemask with a flexible, integrated opto-chemical gas sensor designed at the University of Granada makes it possible to ascertain the level of CO2 rebreathed in real time, using a smartphone application. This is low cost, scalable, reliable, and convenient, the researchers say.

Details of the design are published in Nature Communications.

Italian research institutes organise COVID-19 hackathon to apply AI in health

A COVID CXR Hackathon has been launched by the Italian Institute of Technology, Fondazione Bruno Kessler and the University of Modena and Reggio Emilia, with an invitation to the international scientific community to apply the most advanced software and analysis models of artificial intelligence to the interpretation of COVID-19 clinical data, with the aim of making the work of doctors in hospital wards easier, and ease the strains the pandemic has put on health systems.

The organisers of the hackathon say automated or semi-automated techniques developed using machine learning could help doctors tell which patients can be treated safely at home, improving planning and allocation of resources.

Participants in the hackathon will have to develop systems capable of processing real data gathered from hospitalised patients in the first wave of the pandemic in early 2020.

The winning proposals will not only be accurate, but must operate in a way that is transparent and understood by healthcare providers who are not artificial intelligence experts. The contributions will be evaluated by a team of doctors and computer scientists.

Alessio Del Bue, head of Pattern Analysis and Computer Vision at the Italian Institute of Technology in Genoa said, “COVID CXR Hackathon was designed to transform the pandemic experience into a driver for the scientific community to show that the development of automated intelligent systems, both for the recognition of images and other types of data, is ready to face the most pressing problems of our society. Discussion with clinicians, companies and industry is critical.”

Researchers develop new way of modelling COVID-19 in mice

Disease models play a major role in COVID-19 research, allowing the study of disease mechanisms and preclinical development of vaccines and treatments. Now a research group at the Medical University of Vienna has developed a new way of modelling COVID-19 in mice, which closely mimics how humans react to the SARS-CoV-2 virus.

There are many similarities between the immune systems of mice and humans, meaning in general that mice make good models of human disease.

However, because of specific genetic and structural differences between mice and humans in the ACE2 receptor by which SARS-CoV-2 enters the host cells, mice are not readily infected with virus variants isolated from human COVID-19 patients.

The researchers have taken SARS-CoV-2 from a human patient and modified it so it can bind to murine ACE2. Animals infected by the modified virus develop symptoms of COVID-19, allowing the study of disease mechanisms and of potential treatments.

It was shown that the immune response in infected mice is similar to that seen in humans.

As an example of the utility of the model, the researchers demonstrated that synthetically produced ACE2, administered by inhalation, can protect against SARS-CoV-2 infection.

Study confirms pulse oximeters give false readings in people of darker skin colour

A warning issued last year by the US Food and Drug Administration drew attention to research showing pulse oximeters that detect blood oxygen levels by shining light through the skin give inaccurate readings in people with darker skin colour.

Now researchers at Nottingham University have quantified the levels of false readings and are about to investigate the impact this has on patients getting the treatment they need, when they need it

The research, published in the European Respiratory Journal, shows that pulse oximeters recorded oxygen levels of nearly 7% higher than was the fact in a group of patients of mixed ethnicity with COVID-19. That compared over-stating oxygen levels in white patients by 3%.

There were also false high readings in patients with of both Black and Asian ethnicity. Levels of blood oxygen are one of the key ways of assessing the severity of COVID-19 infections, and these incorrect measurements could delay people being admitted to hospital and receiving the best and most timely treatment.

The researchers used electronic datasets that are collected for clinical use in real time, but archived and available to answer important clinical questions and improve both patient care and safety.

They compared the difference in blood oxygen levels as measured by pulse oximetry and by arterial blood gas tests, which involve measuring oxygen levels directly in a blood sample.

There were differences in oxygen levels between the pulse oximetry and arterial blood gas readings in all groups. The highest difference was in the mixed ethnicity group, which was nearly 7% higher in the oximetry reading.

The smallest difference was in the white group, where the pulse oximeter reading was 3.2% higher than in the gold standard arterial blood gas. A reading of 5.4% higher using pulse oximetry was seen in the Black group and 5.1% higher in the Asian cohort.

The differences between the readings were in the clinically important range of 85 to 89% oxygen saturation, when many clinical decisions are made.

“This data builds on what we know, which is that patients with darker skin have less accurate oxygen measurements using the pulse oximeters. Any error of measurement of oxygen levels will make assessing the severity of COVID-19 infection more difficult, and may delay delivery of timely medical care,” said Andrew Fogarty, from the School of Medicine at Nottingham University, lead author of the study. “We are now exploring the impact of this on clinical outcomes to see if it may have led to any issues in escalating treatment intensity for our patients.”

Norwegian biotech’s cancer drug selected for EU funded study in treating COVID-19

BerGenBio and the Oslo University Hospital are to test the Norwegian biotech’s cancer drug bemcentinib, in hospitalised COVID-19 patients, as part of the EU-SolidAct trial.

The EU-funded SolidAct is a pan-European programme for setting up rapid and coordinated studies of drugs to treat COVID-19 during the ongoing pandemic, under a master protocol.

As part of the trial, bemcentinib will be studied in up to 500 hospitalised COVID-19 patients, with Bergen-based BerGenBio providing the drug and meeting incremental costs related to the bemcentinib sub-protocol.

The first drug studied under the EU-SolidAct platform was Eli Lilly’s baricitinib, which is now being evaluated by the European Medicines Agency. Bemcentinib was selected by an international expert group to be the second drug to be studied in EU-SolidAct, which has set up clinical sites in 15 countries.

In cancer, bemcentinib acts to block expression of the enzyme Axl kinase, which is central to a key mechanism by which cancer evades the immune system. The oral, once-a-day, drug is currently in phase II development in a number of cancers.

It was first tested in COVID-19 patients in the UK Accord trial, on the basis of preclinical data showing Axl kinase inhibition blocks viral entry and enhances the interferon response, a key cellular defence mechanism against viral infection.

As the COVID-19 pandemic continues to evolve, it is even more important to identify new therapies for hospitalised patients that have a mechanism of action effective across emerging variants of SARS-CoV-2, said Martin Olin, CEO of BerGenBio. “The EU-SolidAct platform provides BerGenBio with a unique opportunity to rapidly study the effectiveness of bemcentinib and to evaluate the promising signals of efficacy that were observed in hospitalised patients requiring oxygen in earlier studies,” he said.

Marius Trøseid, associate professor at Oslo University Hospital, and chief Investigator of EU-SolidAct agreed. “With new variants and evolving patient populations, it is increasingly important to have more treatment options for preventing need of intensive care and long hospitalisations.”

New spin out formed to commercialise French nasal vaccine against COVID-19

Since June 2020 researchers at the University of Tours have been working on the development of a nasal vaccine against the SARS-CoV-2 virus.

To date, pre-clinical tests have demonstrated efficacy of the vaccine after two nasal immunisations delivered three weeks apart, both in terms of the immune response and early neutralisation of the original virus and its variants,

These results were subsequently confirmed at the end of 2021 in rodent studies that validated its effectiveness against the Delta variant. The vaccine, consisting of the spike protein and non-mutated viral proteins, is therefore seen as likely to protect against Omicron also.

Now, a start-up LoValTech (for Loire Valley Technology) has been granted an exclusive licence to commercialise the nasal vaccine following its spin out from the university earlier this month.

The company has raised a total of €2.4 million in grants from various funding bodies for further development of the vaccine, including for the production of the vaccine proteins for clinical trials.

LoValTech will also work with collaborators to develop a device for administering the vaccine.

Discussions on the design of the clinical trials and the drafting of the phase I protocol are due to start over the next few weeks.

Air quality improvements during the first lockdown in Europe may have prevented more than 800 deaths

More than 800 deaths across Europe were avoided as a result of the improved air quality resulting from the government measures taken to limit the spread of the SARS-Cov-2 virus.

Paris, London, Barcelona, and Milan were among the top six cities with the highest number of avoided deaths, according to new research funded by the European Centre for Medium-Range Weather Forecasts on behalf of the Copernicus Atmosphere Monitoring Service and led by a team at the London School of Hygiene & Tropical Medicine (LSHTM).

The study compared government policies from 47 European cities from February to July 2020 and estimated the changes in pollution levels and related number of deaths avoided during the first wave of COVID-19 pandemic.

Measures such as school and workplace closures, cancelling public events, and stay-at-home requirements had the strongest effect on reducing NO2 levels. This is linked to the reduction in road transport and local mobility which is known to be a contributor to NO2 air pollution.

Spanish, French and Italian cities had the largest decrease in NO2, of between 50% and 60% during the period.

Although strong decreases in NO2 were observed, levels of fine particulate matter were reduced more modestly since they are also produced by natural sources, including wildfires and dust, and other emission sources like residential activities, that were slightly increased during lockdown.

“The lockdown during the first wave of the COVID-19 pandemic created immense health and social costs, however, it has offered unique conditions to investigate potential effects of strict policies to reduce pollution levels in urban areas,” said Antonio Gasparrini, professor of biostatistics and epidemiology at LSHTM and senior author of the study. “This ‘natural experiment’ has given us a glimpse of how air quality can be improved by drastic public health measures that would be difficult to implement in normal times. The information can be important to design effective policies to tackle the problem of pollution in our cities.”

Although all cities experienced a slight increase in air pollution levels after the strong decline in March and April 2020, levels remained below business-as-usual scenario estimates throughout the period studied. Restrictions on internal and international travel showed a minor impact on the local pollution levels.

Austrian research shows COVID-19 booster vaccination is safe and effective in immunosuppressed patients

Patients who are receiving immunosuppressive therapy, such as cancer chemotherapy or treatment for rheumatoid arthritis, often do not respond to primary COVID-19 vaccination, and have an increased risk for severe COVID-19 disease.

Until now, it was not clear whether these at risk patients can benefit from an additional booster vaccination.

Now, new research by the Medical University of Vienna has shown that a third vaccination is safe and effective in those patients who were initially unable to produce antibodies after vaccination. The study was recently published in the journal Annals of the Rheumatic Diseases.

Researcher Michael Bonelli was able to show that even patients being treated with the rheumatoid arthritis drug rituximab, who did not respond to primary vaccination are able to develop an immune response following a booster vaccination.

The study is the first randomised, blinded trial to show the efficacy and safety of a booster vaccination in patients without an immune response after two vaccinations because of rituximab treatment.

An ongoing study is investigating the efficacy of a forth vaccination in patients at risk.

Pfizer and BioNTech start trial of vaccine aimed against Omicron

Pfizer and BioNtech said they have begun a clinical study of an updated version of their COVID-19 vaccine, which is specifically designed to protect against the Omicron variant.

The study will have three cohorts, comparing the current Pfizer-BioNTech COVID-19 vaccine with the Omicron-based vaccine.

“While current research and real-world data show that boosters continue to provide a high level of protection against severe disease and hospitalisation with Omicron, we recognise the need to be prepared in the event this protection wanes over time and to potentially help address Omicron and new variants in the future,” said Kathrin Jansen, head of vaccine R&D at Pfizer.

“Emerging data indicate vaccine-induced protection against infection and mild to moderate disease wanes more rapidly than was observed with prior strains,” said Ugur Sahin, CEO of BioNTech. “This study is part of our science-based approach to develop a variant-based vaccine that achieves a similar level of protection against Omicron as it did with earlier variants but with longer duration of protection.”

UK/German study finds out why Omicron causes less severe disease

The SARS-CoV-2 Omicron variant causes less severe disease than the Delta variant that went before, even though it is better at escaping immune protection provided by vaccination or previous infections.

The reasons for this have so far remained elusive, but now a new study by scientists at Kent University and the Goethe-University Frankfurt has shown Omicron is particularly sensitive to inhibition by the interferon response, a non-specific immune response that can be triggered by every cell in the body.

They say this explains why COVID-19 patients infected with the Omicron variant are less likely to experience severe disease.

Martin Michaelis of the School of Bioscience at Kent University, said, “Our study provides for the first time an explanation why Omicron infections are less likely to cause severe disease. This is due to [the fact that] Omicron, in contrast to Delta, does not effectively inhibit the host cell interferon immune response.”

Although more transmissible, the study showed Omicron remains sensitive to eight of the most important antiviral drugs and drug candidates for the treatment of COVID-19. The same is not true of monoclonal antibody drugs designed to lock onto and neutralize the virus, which are mostly not effective against the Omicron variant.

The cell culture study the researchers carried out does not exactly reflect the more complex situation in humans, noted Jindrich Cinatl of the Institute of Medical Virology at the Goethe-University, but he said, “Our data provide encouraging evidence that the available antiviral COVID-19 drugs are also effective against Omicron.“

Canadian researchers uncover molecular structure of Omicron’s spike protein

Researchers at the University of British Columbia faculty of medicine have conducted the world’s first molecular-level structural analysis of the Omicron variant spike protein by which the virus gets access to human cells.

The Omicron variant has an unprecedented 37 mutations on its spike protein - three to five times more than previous variants.

The near single atom resolution analysis, published in the journal Science, reveals how the heavily mutated Omicron variant attaches to and infects human cells.

Understanding the molecular structure of the viral spike protein will inform the development of more effective therapies against Omicron and related variants in the future, said Sriram Subramaniam, professor in the department of biochemistry and molecular biology and lead author of the paper. “By analysing the mechanisms by which the virus infects human cells, we can develop better treatments that disrupt that process and neutralise the virus,” he said.

The structural analysis revealed that several mutations create new salt bridges (bonds between oppositely charged proteins) and hydrogen bonds between the spike protein and the ACE2 receptor on human cells. The researchers say these new bonds appear to increase the binding affinity, creating stronger attachments between the virus and human cells. However, another mutation was shown to decrease the strength of these attachments.

“Overall, the findings show that Omicron has greater binding affinity than the original virus, with levels more comparable to what we see with the Delta variant,” said Subramaniam. “It is remarkable that the Omicron variant evolved to retain its ability to bind with human cells despite such extensive mutations.”

In other experiments, the researchers showed the Omicron spike protein has an increased ability to evade antibody drugs. In contrast to previous variants, Omicron showed measurable evasion from all six monoclonal antibodies tested, with complete escape from five. The variant also displayed increased evasion of antibodies in blood samples from vaccinated individuals and unvaccinated COVID-19 patients.

Antibody drugs rushed through approvals withdrawn for lack of efficacy against Omicron

The US Food and Drug Administration has revised the authorisations for two monoclonal antibody drugs bamlanivimab and etesevimab (administered together) and REGEN-COV (casirivimab and imdevimab) to limit their use to only when a patient is not infected by the Omicron variant that is now causing most infections worldwide.

The move comes on the heels of data showing these treatments are highly unlikely to be active against Omicron.

Current monoclonal antibodies are designed to neutralise SARS-CoV-2 by binding to the spike protein seen in the original variant of the virus that emerged in Wuhan. The mutations in the Omicron variant means this mechanism of action is no longer effective.

French biotech Valneva says booster dose effective against Omicron

Valneva announced results from an initial laboratory study demonstrating that antibodies induced by three doses of its whole virus, inactivated COVID-19 vaccine candidate, VLA2001, neutralise the Omicron variant.

Blood samples from 30 participants in the phase I/II trial of VLA2001-201 were used in a pseudovirus assay to analyse neutralisation of the original Wuhan variant of SARS-CoV-2, as well as the Delta and Omicron variants.

All 30 samples presented neutralising antibodies against the ancestral virus and Delta variant, and 26 samples (87%) presented neutralising antibodies against the Omicron variant. The mean reduction of neutralisation relative to the ancestral virus was 2.7-fold for Delta and 16.7-fold for Omicron.

Juan Carlos Jaramillo, chief medical officer of Valneva, said, “We are extremely pleased with these results, which confirm the potential for broad-spectrum protection of our inactivated, adjuvanted whole virus vaccine and its ability to address currently circulating variants of concern.

“We continue to believe that VLA2001 could be an important component of the fight against COVID-19, and Valneva remains fully committed to bringing VLA2001 to people who need it as soon as we can,” he said.

Valneva is continuing to provide data to the European Medicines Agency, the UK Medicines and Healthcare products Regulatory Agency, and the National Health Regulatory Authority in Bahrain, as part of the rolling submissions process for initial approval of VLA2001. The company continues to expect to complete these submissions in time to receive potential regulatory approvals in the first quarter of 2022.

Valneva announced in November 2021 that the European Commission signed an agreement for the company to supply up to 60 million doses of VLA2001 over two years – including 24.3 million doses in 2022. Delivery of the vaccine in Europe is currently expected to begin in April 2022, subject to approval by the EMA.

Public more likely to support COVID-19 rules if suggested by experts not politicians

Policies to tackle COVID-19 are more likely to get broad public support if they are proposed by experts or by politicians from cross-party coalitions, rather than from politicians from a single ruling party, according to a new study of seven countries.

Public behaviour and support for measures such as facemasks or social distancing have been crucial in tackling the worldwide pandemic. Yet, it has also been difficult to secure and maintain that support, and to avoid debates getting polarised.

The research found that polarisation emerges when policies are associated with opposing political parties and politicians, but that people have a high level of confidence that science experts will act in the public’s best interest.

The COVID pandemic provided a unique opportunity to study this issue. It was a new threat and one that was experienced simultaneously across the world, allowing for international comparisons.

The research team included colleagues from the UK, US, Sweden, Israel, Austria, Italy and Singapore and involved 13,000 participants in 7 countries: UK, US, Brazil, Israel, Italy, Sweden and South Korea. These countries display a range of different political systems and parties in government and varying experiences of COVID and responses to it.

In each country, participants were asked first about their overall political views, using a measure called affective polarisation: their feelings towards liberal and conservative politicians and towards experts.

They were then asked to give their views on two COVID policies. Both involved restrictions, but one emphasised more stringent public health measures to keep case numbers down, while the other involved fewer restrictions for economic recovery.

Respondents in all countries supported policies proposed by experts and bipartisan coalitions, more than those proposed by either liberal or conservative elites.

Italian research shows Russia’s Sputnik V COVID-19 vaccine provides protection against Omicron variant

A comparative study conducted at the Spallanzani Institute in Rome, the leading Italian research institute for infectious diseases, by a joint Italian-Russian team of researchers has shown that the Sputnik V coronavirus vaccine induces more than two times higher levels of virus neutralising antibodies to the Omicron variant than two doses of Pfizer/BioNTech vaccine.

The study was conducted on comparable blood samples from individuals dosed with Sputnik V and Pfizer’s vaccines.

Among all samples, 74.2% of Sputnik V-vaccinated blood samples were able to neutralise Omicron, compared to 56.9% of samples from Pfizer-vaccinated people.

The data support the results of a recent laboratory study by the Gamaleya Centre in Moscow, where Sputnik V was developed, also demonstrating that Sputnik V induces robust neutralising antibody response to Omicron variant.

Sputnik V is currently approved in 71 countries with a total population of over 4 billion people. Its safety and efficacy have been demonstrated in more than 30 studies and real-world data publications from more than 10 countries.

First dual action COVID-19 drug could work against all variants

A research team led by virologist Stephan Ludwig, at the Institute of Virology, University of Münster, has demonstrated that a drug targeting RNA viruses has the dual action of preventing replication of SARS-CoV-2 in human cells and of blocking the exaggerated immune response seen in severe cases of COVID-19.

The data, published in Cellular and Molecular Life Sciences, provided the basis for approval to conduct an ongoing phase II clinical trial.

“In the results we have published, we have been able for the first time to show such a dual action for an anti-COVID 19 agent,” Ludwig said.

The drug in question, Zapnometinib, originally under development as an anti-flu medication, was shown to be effective in a variety of cell culture models, including showing activity against all tested variants of SARS-CoV-2. That implies it will have broad applicability against any emerging variants in the future. Animal testing to confirm this is currently underway, as the clinical trial progresses.

Zapnometinib, which is being developed by German biotech Atriva Therapeutics, inhibits the Raf/MEK/ERK signalling pathway that is involved in the replication of many RNA viruses, including flu, hantavirus, respiratory syncytial virus and also coronaviruses.

“Positive results from the still ongoing clinical study in humans might already lead to an emergency approval this year for a new, broadly effective COVID-19 medication,” said Ludwig.

In April 2021 Atriva was awarded €11.4 million by the German Federal Ministry of Education and Research (BMBF) to finance the phase II study. The funding was part of a €50 million BMBF programme for COVID-19 therapies, awarded to eight companies.

Protective gene variant against COVID-19 identified

An international metastudy led by researchers at Karolinska Institutet has identified a specific gene variant that protects against severe COVID-19 infection.

The researchers homed in on the variant by studying people of different ancestries, which they say highlights the importance of conducting clinical trials that include people of diverse descent.

Previous studies, mainly involving people of European ancestry, found individuals carrying a particular segment of DNA that encodes for genes in the immune system, have a 20% lower risk of developing a severe COVID-19 infection.

This region of DNA is, however, packed with numerous genetic variants, which makes it challenging to pinpoint the one that could potentially serve as a drug target to develop treatments for severe COVID-19 infection.

A small piece of this DNA region is the same in people of both African and European ancestries, leading the researchers to look for individuals of predominantly African ancestry who had the same protection against COVID-19 as those of European ancestry and enabling them to identify the gene variant of interest.

The analysis included 2,787 hospitalised COVID-19 patients of African ancestry in the US and 130,997 people in a control group from six cohort studies. Eighty percent of individuals of African ancestry carried the protective variant. The outcome was compared with a previous metastudy of individuals of European heritage.

The COVID-19 pandemic has spurred considerable collaboration among researchers in different parts of the world, which has made it possible to study genetic risk factors in a wider diversity of individuals than previously. Even so, the majority of all clinical research is still being done on individuals of predominantly European descent.

“This study shows how important it is to include individuals of different ancestries. If we had only studied one group, we would not have been successful in identifying the gene variant in this case,” said Hugo Zeberg, assistant professor in the department of Neuroscience at Karolinska Institutet, co-author of the research published in Nature Genetics.

Genetic risk factor for COVID-19-related loss of smell or taste identified

A genetic risk factor that influences whether an individual is likely to experience a loss of smell or taste as symptoms of COVID-19 has been discovered by the US consumer genetic testing company 23and Me.

Loss of smell or taste are recognised symptoms of COVID-19 but not all individuals infected with SARS-CoV-2 experience them, and the mechanisms responsible are unclear.

Adam Auton and colleagues performed a genome-wide association study using online survey data collected from 69,841 (63% female; 37% male) research participants aged over 18 years, living in the US and the UK. They found that a set of variants located near the two genes, UGT2A1 and UGT2A2, increased the likelihood that an individual will experience a loss of smell or taste following SARS-CoV-2 infection by 11%.

Both genes encode enzymes that are expressed in cells that line the inside of the nose and are involved in eliminating odorants that bind to receptors involved in smell detection.

This discovery provides clues into the biological mechanisms that underlie COVID-19-related loss of smell or taste, the researchers say. The details are published in Nature Genetics.

One in 10 people potentially infectious past the 10-day COVID-19 quarantine period

A study led by Exeter University and published in the International Journal of Infectious Disease has found that 13% of people who test PCR positive for SARS-CoV-2 still exhibited clinically-relevant levels of virus after 10 days.

The researchers used a new test that can detect if virus is still active, meaning people might still be infectious. Some people in the study retained clinically relevant levels of virus for up to 68 days. The researchers say the new test they used should be applied in settings where people are vulnerable, to stop the spread of COVID-19.

Conventional PCR works by testing for the presence of viral fragments. While it is possible to tell if someone has recently had the virus, it does not detect whether it is still active. The new test gives a positive result only when the virus is active and potentially capable of onward transmission.

The test was applied to samples from 176 people in Exeter who had tested positive on standard PCR tests. The data shows that at five days, 30% still exhibited clinically-relevant levels of potentially active virus.

Merlin Davies, of Exeter University Medical School, said, “In some settings, such as people returning to care homes after illness, continuing to be infectious after ten days could pose a serious public health risk. We may need to ensure people in those settings have a negative active virus test to ensure people are no longer infectious. We now want to conduct larger trials to investigate this further.”

AstraZeneca says booster doses of its COVID-19 vaccine are effective against variants – including Omicron

Positive results from a preliminary analysis of an ongoing safety and immunogenicity trial of AstraZeneca’s vaccine given as a third dose booster, show there is an increased immune response to Beta, Delta, Alpha and Gamma SARS-CoV-2 variants, while a separate analysis of samples from the trial showed increased antibody response to the Omicron variant.

The results were observed among individuals previously vaccinated with either the AstraZeneca vaccine, or Pfizer or Moderna’s mRNA vaccines.

A separate phase IV trial showed that a third dose of the AstraZeneca vaccine substantially increased antibody levels following primary vaccination with CoronaVac, which is manufactured by the Chinese company Sinovac Biotech.

Astrazeneca said these data add to the growing body of evidence supporting the use of its vaccine as a third dose booster, irrespective of the primary vaccination received.

Mene Pangalos, executive vice president of biopharmaceuticals R&D at AstraZeneca, said the vaccine has already protected hundreds of millions of people from COVID-19 and these data show that it has an important role to play as a booster, including when used after other vaccines. “We will continue to progress regulatory submissions around the world for its use as a third dose booster,” he said.

EMA and other regulators meet to agree requirements for adapted COVID-19 vaccines

The European Medicines Agency said it co-chaired a meeting of regulators from around the world to discuss the global regulatory response to the COVID-19 Omicron variant.

The goal of the meeting was to review available evidence for the effectiveness of the approved COVID-19 vaccines against the Omicron and reach alignment on the key regulatory requirements to support development of a possible adapted vaccine.

Emer Cooke, EMA executive director, told the meeting the discussion was not only about the regulatory response to Omicron, but is also part of setting the scene for a more strategic discussion about what types of vaccines might be needed in the long-term to adequately manage COVID-19.

“These decisions are not for regulators alone. Collaboration is needed across all the actors in this space, including public health decision makers at national, regional and global level,” Cooke said.

While most available data suggest that the approved COVID-19 vaccines are losing effectiveness in protecting against infection and mild disease, they continue to provide high protection against serious infections.

EMA said details on the discussions and the outcomes of the meeting will be published in the coming days. Meanwhile, the agency said its preliminary assessment of the available data indicates COVID-19 vaccines remain effective against severe disease and hospitalisation caused by the Omicron variant.

Although Omicron appears to be more infectious than other variants, studies from South Africa, UK and some EU countries show a lower risk of being hospitalised after infection with Omicron; based on these studies, the risk is currently estimated to be between a third and half of the risk with the Delta variant.

However, results from recently published studies show that vaccine effectiveness against symptomatic disease is lower for Omicron than for other variants and tends to wane over time. As a result, more vaccinated people are likely to develop breakthrough disease due to Omicron.

The latest evidence, which includes real-world effectiveness data, also suggests that people who have had a booster dose are better protected than those who have only received their primary course.

EMA said it will continue to review data on vaccine effectiveness and severity of the disease. The outcome of these assessments may impact future vaccination strategies recommended by experts in the EU.

New method analyses SARS-CoV-2 sequence data to predict which variants are high risk

A collaboration between BioNTech and UK artificial intelligence specialist Instadeep has led to the development of a new computational method that analyses worldwide genome sequencing data to pick out high-risk variants of SARS-CoV-2.

The Early Warning System (EWS), based on artificial intelligence (AI) calculated immune escape and fitness metrics, combines structural modeling of the spike protein by which the virus enters host cells, and AI algorithms, to quickly flag potential high-risk variants. It can pick up sequences uploaded to SARS-CoV-2 data repositories within less than a day, based on metrics scoring their fitness and their immune escape properties.

The two companies validated these predictions using experimental data generated in-house and publicly available data.

During a trial period, the system identified more than 90% of the World Health Organisation (WHO)-designated variants. The WHO-designated variants of concern, Alpha, Beta, Gamma, Theta, Eta and Omicron were detected by the EWS in the same week as their sequences were first uploaded, with the Omicron variant ranked as a high-risk variant the same day its sequence became available.

The results from the study underline that the EWS is capable of evaluating new variants in minutes and risk-monitoring variant lineages nearly in real-time. It is also fully scalable as new variant data becomes available.

“With the advanced computational methods we have been developing over the past months we can analyse sequence information of the spike protein and rank new variants,” said Ugur Sahin, CEO and co-founder of BioNTech. “Early flagging of potential high-risk variants could be an effective tool to alert researchers, vaccine developers, health authorities and policy makers, thereby providing more time to respond to new variants of concern.”

The data published as a pre-print is the result of a collaboration established between BioNTech and InstaDeep in November 2020. As part of the collaboration, the companies formed a joint AI innovation lab in London and Mainz, Germany.

Molecule developed by researchers in Finland immediately inactivates SARS-CoV-2, offering short-term protection

A new molecule developed by researchers at Helsinki University protects against SARS-CoV-2 infection for at least eight hours, and in contrast to vaccines, is effective immediately after administration as a nasal spray.

“In animal models, nasally administered TriSb92 offered protection against infection in an exposure situation where all unprotected mice were infected,” said Anna Makela, first author of the study, which has been published as a preprint.

The molecule, TriSb92, inhibits the functioning of the spike protein on the surface of the SARS-CoV-2 virus.

“Targeting this inhibitory effect of TriSb92 to a site on the coronavirus spike protein common to all variants of the virus makes it possible to effectively inhibit the ability of all known variants, Omicron included, to infect people,” Makela said.

EMA evaluating Pfizer’s COVID-19 oral antiviral Paxlovid

The European Medicines Agency said it has started evaluating Pfizer’s oral antiviral drug Paxlovid in the treatment of mild-to-moderate COVID-19 in adult and adolescent patients who are at high risk of progression to severe disease under a reduced timeline, and could issue an opinion within weeks.

The expedited timeframe is possible because EMA has already started a rolling review, which included in vitro, animal and clinical studies, including one looking at use of Paxlovid in non-hospitalised, unvaccinated patients with COVID-19, who had symptomatic disease and at least one underlying condition putting them at risk of severe disease.

Paxlovid reduces the ability of SARS-CoV-2 to cause serious infections by blocking the activity of an enzyme the virus needs to multiply.

T cells generated in response to common colds can protect against SARS-CoV-2 infection

A new study has provided direct evidence of a protective role for T cells generated in response to common colds caused by coronaviruses.

While previous studies have shown that T cells induced by other coronaviruses can recognise SARS-CoV-2, the research by scientists at Imperial College London is the first to show the presence of these T cells at the time of SARS-CoV-2 exposure influences whether someone becomes infected.

The researchers also say their findings could inform the design of a second generation, universal vaccine that could prevent infection from current and future SARS-CoV-2 variants, including Omicron.

Rhia Kundu, first author of the study said, “Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why. We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection.”

The study, which started in September 2020 when most people in the UK had neither been infected nor vaccinated against SARS-CoV-2, involved 52 people who lived with someone with PCR-confirmed SARS-CoV-2 infection, and who had therefore been exposed to the virus. The participants did PCR tests at the outset and 4 and 7 days later, to determine if they developed an infection.

Blood samples from the 52 participants taken within 1-6 days of them being exposed to the virus were analysed for pre-existing T cells induced by previous common cold coronavirus infections that also cross-recognise proteins of the SARS-CoV-2 virus.

The researchers found that there were significantly higher levels of these cross-reactive T cells in the 26 people who did not become infected, compared to the 26 people who did become infected.

These T cells targeted internal proteins within the SARS-CoV-2 virus, rather than the spike protein on the surface of the virus.

The current COVID-19 vaccines do not induce an immune response to these internal proteins, which researchers say, offer a new vaccine target that could provide long-lasting protection, because T cell responses persist longer than antibody responses, which wane within a few months of vaccination.

Leiden University to co-develop nasal spray COVID-19 vaccine

Dutch biotech Intravacc has formed a partnership with Leiden University Medical Centre (LUMC) to develop and evaluate a new nasal spray COVID-19 vaccine in a clinical phase I/II study.

The vaccine, Nanovac, is based on microscopic soluble nanospheres, containing synthetic mini proteins administered as a nasal spray, to directly protect the upper respiratory tract including nasal passages and throat, before the virus reaches the lungs.

The design and route of administration makes the vaccine broadly protective, harnessing both arms of the immune system against COVID-19.

A team led by Luis Cruz at LUMC’s Translational Nanobiomaterials and Imaging department has spent more than a year working on the nasal spray vaccine. Preclinical studies in animals showed positive results.

The phase I/II clinical study is led by Leo Visser of the Infectious Diseases Department at LUMC.

Nanovac is intended to protect against current and future COVID-19 variants, by generating an immune reaction not only against the spike protein the virus uses to enter human host cells, but also other conserved epitopes derived from distinct coronavirus proteins.

In addition, the product includes an adjuvant to enhance the immune response it generates.

Intravacc says the vaccine can be produced rapidly in large quantities at a lower cost than existing vaccines, and can be stored at room temperature.

New type of mRNA COVID-19 vaccine delivers positive data

US biotech Gritstone Bio has announced positive phase I clinical data from the first cohort of participants in the UK trial of its self-amplifying mRNA (samRNA) vaccine, demonstrating both strong neutralising antibody responses to the spike protein and robust T cell responses.

The vaccine is being assessed for use as a booster against SARS-CoV-2 in healthy adults who previously received two doses of AstraZeneca's first-generation COVID-19 vaccine.

Andrew Allen, CEO of Gritstone said, “As we have seen with the Omicron variant, viral surface proteins such as spike are mutating at a high rate, leaving the immunity provided by spike-dedicated vaccines vulnerable to variants containing numerous spike mutations. We designed our COVID-19 vaccines to drive broad CD8+ T cell immunity, an additional key layer of protection against viruses.”

Andrew Ustianowski, lead investigator for the study at Manchester University and clinical lead for the National Institute for Health Research COVID-19 vaccine research programme, said the initial data strongly support the approach to T cell priming and potent neutralising antibody generation with a dose of samRNA potentially up to 10-fold lower than that required for first generation mRNA vaccines.

“We are increasingly realising the importance of both the T cell response and non-spike protein targets for protection against severe disease, hospitalisation, and death, and to allow protection against current and future variants of the virus,” Ustianowski said.

The trial is ongoing in the UK.

Institutional investors tell pharma companies vaccine equity no longer optional

A group of over 65 leading institutional investors is calling on COVID-19 vaccine manufacturers to move quickly to increase the availability and deployment of vaccinations around the world.

An investor statement has been drawn up to that end under the leadership of the Dutch fund Achmea Investment Management and letters have been sent to pharmaceutical companies asking them to make the global availability of vaccines part of the remuneration policy of managers and directors.

In total, the more than 65 asset managers, pension funds and insurers who have joined the initiative represent total assets of €3,000 billion.

The World Health Organisation (WHO) has said affordable vaccination for the whole world is vital to combat the pandemic, from both the humanitarian and economic viewpoints. The WHO has outlined a clear path to achieving this and the institutional investors want pharmaceutical companies to make these WHO targets part of their remuneration policy.

Rogier Krens, chief investment officer of Achmea said, “We will only be able to get this pandemic under control by working together. Our view is that pharmaceutical companies have a duty to do their utmost on this, but unfortunately we see that they are lagging behind. In addition, the business case is clear: new variants threaten the recovery of economies around the world.”

Preprints shown to be a good way to disseminate COVID-19 research

While physicists have long posted preprints of their research in advance of peer review, biologists have held back. The COVID-19 pandemic has changed that, with preprints in the biomedical sciences being posted and accessed at unprecedented rates and drawing widespread attention from the general public, press and policymakers for the first time.

This has sharpened longstanding questions about the reliability of information shared prior to journal peer review. In particular, do the findings shared in preprints typically withstand the scrutiny of peer review, or are conclusions likely to change in the version of record?

Researchers have assessed preprints from the bioRxiv and medRxiv servers that had been posted and subsequently published in a journal through 30th April 2020, during the initial phase of the pandemic response. They used a combination of automatic and manual annotations to quantify how an article changed between the preprinted and published version.

They found that the total number of figures and tables hardly differed between preprint and published articles. 7.2% of non-COVID-19 and 17.2% of COVID-19-related abstracts changed from the preprint to the peer reviewed journal paper, but the majority of these changes do not qualitatively change the overall conclusions that were drawn.

The data analysing abstracts suggests that the main conclusions of 93% of non-COVID-related life sciences articles do not change from their preprint to final published versions, with only one out of 184 papers in the analysis contradicting a conclusion made by its preprint.

“Our data provides confidence in the use of preprints for dissemination of research,” the researchers conclude.

Vaccines and monoclonal antibodies less effective against Omicron variant of SARS-CoV-2

With the Omicron variant of SARS-CoV-2 spreading at an alarming rate and poised to replace the Delta variant, German scientists led by Stefan Pöhlmann and Markus Hoffmann from the German Primate Centre at the Leibniz Institute for Primate Research in Göttingen have assessed the efficiency of vaccines and therapeutic antibodies against Omicron, looking at how efficiently it is neutralised by antibodies from recovered and vaccinated people.

The team was able to show that antibodies from people who recovered from a natural infection hardly inhibit the Omicron variant. Antibodies produced after two doses of the Pfizer/BioNTech vaccine also showed significantly reduced efficacy.

Better inhibition was observed after Pfizer boosters and after heterologous vaccination with the AstraZeneca and Pfizer vaccines.

In common with other researchers, the German scientists found that most of the therapeutic antibodies evaluated in the study are not effective against the Omicron variant.

Currently, combinations of the antibodies Casirivimab and Imdevimab, and Etesevimab and Bamlanivimab are used to treat COVID-19, but these drugs do not work against Omicron. Only one antibody, GlaxoSmithKline’s Sotrovimab, retains its effect.

"Our cell culture studies suggest that most antibodies currently available for COVID-19 therapy will be ineffective against Omicron. Sotrovimab is an exception and could become an important treatment option for Omicron-infected patients," Hoffmann said.

Fifth COVID-19 vaccine approved in Europe

US biotech Novavax has received EU marketing approval for COVID-19 vaccine Nuvaxovid, which becomes the fifth vaccine approved by the European Medicines Agency.

The approval is based on results from two main clinical trials involving over 45,000 people.

The first study, conducted in Mexico and the US, found a 90.4% reduction in the number of symptomatic COVID-19 cases from 7 days after the second dose in people who received Nuvaxovid (14 cases out of 17,312 people), compared with people given placebo (63 out of 8,140 people)..

The second study conducted in the UK also showed a similar reduction in the number of symptomatic COVID-19 cases in people who received Nuvaxovid (10 cases out of 7,020 people), compared with people given placebo (96 out of 7,019 people). In this study, the vaccine efficacy was 89.7%.

Taken together, the results of the two studies show a vaccine efficacy for Nuvaxovid of around 90%. The original strain of SARS-CoV-2 and the Alpha and Beta variants of concern were the most common viral strains circulating when the studies were ongoing. There is currently limited data on the efficacy of Nuvaxovid against the Omicron variant which is now spreading rapidly across Europe.

Nuvaxovid contains a synthetic version of the spike protein found on the surface of SARS-CoV-2, along with an adjuvant to help strengthen immune responses to the vaccine.

Protection offered by AstraZeneca COVID-19 vaccine declines after three months

A new study based on real world evidence from Scotland and Brazil suggests that booster programmes are needed to help maintain protection from severe disease in those vaccinated with AstraZeneca’s vaccine.

The researchers analysed data from two million people in Scotland and 42 million people in Brazil. They found that in Scotland, when compared with two weeks after receiving a second dose, there was approximately a fivefold increase in the chance of being hospitalised or dying from COVID-19 at around five months after being double vaccinated.

The decline in effectiveness begins to first appear at around three months, when the risk of hospitalisation and death is double that of two weeks after the second dose. Similar numbers were seen for Brazil.

The researchers were able to compare data between Scotland and Brazil as they had a similar interval between doses, of 12 weeks, and the same initial prioritisation of who was vaccinated – people at highest risk of severe disease and healthcare workers.

The dominant variant was different in each country during the study period – Delta in Scotland and Gamma in Brazil – meaning the decline in effectiveness is likely because of vaccine waning and the impact of variants, the researchers say.

The study also estimated vaccine effectiveness at fortnightly intervals by comparing outcomes of people who have been vaccinated with those who are unvaccinated.

Aziz Sheikh, director of Edinburgh University’s Usher Institute and study lead, said, “Vaccines have been a key tool in fighting the pandemic, but waning in their effectiveness has been a concern for a while. By identifying when waning first starts to occur in the AstraZeneca vaccine, it should be possible for governments to design booster programmes that can ensure maximum protection is maintained.”

Spanish scientists develop new sensor to detect SARS-CoV-2 in saliva

Scientists at the Universidad Carlos III de Madrid have developed the first photo-electrochemical sensor that can detect the SARS-CoV-2 virus in a saliva sample. This sensor, which uses a type of artificial antibody called an aptamer, is claimed to be more sensitive that antigen-based sensors and to detect the virus more quickly and cheaply than PCR tests.

These new sensors can be incorporated into portable diagnostic systems and are easy to use.

The researchers say the sensor has a wide range of sensitivity to different virus concentrations, meaning it is capable of detecting concentrations below 0.5 nanomolar, that is typical in patients who have not yet developed COVID symptoms. It works at concentrations of up to 32 nanomolar, providing a tool for monitoring the progress of infection in patients.

“The advantage over current antigen-based sensors is the greater sensitivity and specificity of the photo-electrochemical sensor measurements, which are comparable to more complex measurements, such as those from fluorescence-based sensors, and they are simpler, cheaper, and faster than PCR-based sensors,” said Mahmoud Amouzadeh Tabrizi, researcher at the university’s Department of Electronic Technology.

This research is being undertaken as part of a project financed by the Regional Government of Madrid and the EU, which brings together scientists from the Madrid region to develop technologies for manufacturing tissue and organs, and to optimise these processes for clinical and industrial application.

GSK and Sanofi say their vaccine works as a booster

A single booster dose of the COVID-19 vaccine being co-developed by Sanofi and GlaxoSmithKline delivered consistently strong immune responses, with neutralising antibodies increasing 9- to 43-fold regardless of the primary vaccine received (AstraZeneca, Johnson & Johnson, Moderna, Pfizer/BioNTech), and for all age groups tested.

The companies said the booster was well tolerated, with a safety profile similar to currently approved COVID-19 vaccines.

However, the ongoing global phase III trial to support approval of the vaccine has been extended into early 2022, in order to accrue more data. That is because at this stage in the pandemic it has been hard to recruit enough people who were infection naïve and had never been infected by SARS-CoV-2, as required by the regulators.

“These preliminary data show we have a strong booster candidate, whatever primary vaccine you have received,” said Thomas Triomphe, executive vice president, Sanofi Pasteur. “While pursuing a phase III trial is a challenge in a quickly shifting pandemic environment, we look forward to seeing the results to support submissions of our booster vaccine as quickly as possible.”

The booster trial is ongoing across sites in multiple countries, including the US, France, and the UK, and is now assessing how effective the vaccine is against the Omicron variant of concern.

The clinical development is being funded by the US Biomedical Advanced Research and Development Authority.

Multiple sclerosis drugs found to cut COVID-19 vaccine effectiveness

Treatments for multiple sclerosis (MS) can reduce the effectiveness of COVID-19 vaccines, according to researchers from Cardiff University and Queen Mary University of London.

Disease-modifying MS drugs affect the immune system, and as vaccines work by triggering the body to produce an immune response, it was suspected this might happen.

The researchers studied almost 500 people with MS. Their findings show that those taking two particular drugs, fingolimod and ocrelizumab, were less likely to produce antibodies in response to AstraZeneca and Pfizer/BioNTech COVID-19 vaccines than people with MS not taking these disease modifying drugs.

The researchers also studied T-cell responses in a small group of study participants who failed to mount an adequate antibody response to COVID-19 vaccination. They found that overall, 40% of this group were able to produce a strong T-cell response.

“People with MS have faced uncertainty during the Covid-19 pandemic as a direct result of their condition and the treatments they take to manage it,” said Ruth Dobson, clinical senior lecturer in neurology at Queen Mary. “Our study provides high-quality evidence that will support clinicians to advise people with MS on treatment options. However, further trials are essential to help us understand how best to balance the risks of potentially suspending or delaying MS treatment with the need to effectively vaccinate people with MS against COVID-19,” she said.

India’s largest vaccines company donates £50M for vaccines research centre at Oxford University

Oxford University is getting £50 million from India’s largest vaccines manufacturers, Serum Life Sciences, to set up a new vaccines research laboratory.

The lab will be built on the same site as the recently announced Oxford University Pandemic Sciences Centre, with the buildings sharing infrastructure and support facilities.

The Serum-funded facility will house over 300 research scientists and will provide the focus and scale for translation of the university’s academic vaccine development programmes.

The new building will house the headquarters and main laboratory space of the Jenner Institute, which collaborated with Serum on the development and global rollout of AstraZeneca’s COVID-19 vaccine, which is based on research carried out at the university. The two are also collaborating on the development of a malaria vaccine.

Adrian Hill, director of the Jenner Institute, said the success of the collaborative programmes on both the malaria and COVID-19 vaccines, “Has highlighted the great potential of partnerships between leading universities and large-scale manufacturers to develop and supply vaccines for very cost-effective deployment at exceptional scale. We look forward to a wider range of vaccine activities in the future, building on this generous support.”

Vaccines shown to induce lower levels of neutralising antibodies against Omicron variant

Researchers from Oxford University have analysed the impact of the Omicron COVID-19 variant of concern on the immune responses generated by vaccination using blood samples from individuals who had previously received two doses of the AstraZeneca or Pfizer/BioNTech vaccines.

They show there was a substantial decrease in the level of neutralising antibodies generated in response to vaccination against, or infection from, COVID-19.

The results indicate that the Omicron variant has the potential to drive a further wave of infections, including among those already vaccinated, the researchers say, though they highlight that there is currently no evidence of increased potential to cause severe disease, hospitalisations or death.

Gavin Screaton, head of the Medical Sciences Division at Oxford University, who led the research said, “These data will help those developing vaccines, and vaccination strategies, to determine the routes to best protect their populations, and press home the message that those who are offered booster vaccination should take it.”

Matthew Snape, professor in paediatrics and vaccinology, said, “These data are important but are only one part of the picture. They only look at neutralising antibodies after the second dose, but do not tell us about cellular immunity.”

The next step for the research will be to use the stored blood samples to assess the impact of booster doses

EMA has started formal review of new COVID-19 antiviral drug

Following an interim recommendation to support governments in deciding on early use of Merck’s COVID-19 antiviral drug Lagevrio, the European Medicines Agency is now reviewing more data from the main clinical study.

The interim recommendation was based on an assessment of data based on 762 subjects. This showed Lagevrio reduced the risk of hospitalisation or death in people with COVID-19 who were at higher risk of severe disease from 14.1% in the placebo group to 7.3% in the Lagevrio group. The study did not include people who had been vaccinated.

The updated results, based on 1,408 subjects, show that Lagevrio reduced the risk of hospitalisation or death in people with COVID-19 who were at higher risk of severe disease from 9.7% in the placebo group to 6.8% in the Lagevrio group.

EMA said it will assess these data as part of the review of the marketing application, but for now the earlier recommendations remain unchanged.

Lagevrio is an oral drug that reduces the ability of SARS-CoV-2 to multiply in the body by increasing the number of mutations in its genetic material, impairing the ability of the virus to multiply.

German biotech gets €20.7M government grant for COVID-19 therapy

Apogenix announced it has received €20.7 million funding from the German Federal Ministries of Health (BMG) and of Education and Research (BMBF), as part of the ‘Clinical development of COVID-19 drugs and their manufacturing’ programme.

The money will be used to finance a phase III clinical trial of Apogenix’s drug asunercept in moderately to severely ill, hospitalised COVID-19 patients and for scaling up its manufacturing.

The German government will fund 80% of these costs, and the remaining 20% will be covered by Apogenix’s main investor dievini Hopp BioTech Holding.

Interim data from an ongoing phase II trial in the treatment of moderately to severely ill COVID-19 patients has provided initial evidence of the efficacy. It is thought asunercept has the potential to treat severely ill COVID-19 patients irrespective of the SARS-CoV2 virus variants.

“It is becoming more and more evident that, in addition to COVID-19 vaccines, there is an urgent need for effective drugs to treat those who develop COVID-19 without or despite vaccination,” said Thomas Hoeger, CEO of Apogenix. Asunercept is expected to prevent the death of immune cells and lung cells that leads to acute respiratory distress syndrome, thus reducing the number of COVID-19 patients who require intensive care.

The phase III trial will recruit hospitalised COVID-19 patients with advanced disease who are being treated with oxygen in addition to standard therapy.

UK data suggests Omicron variant can outperform Delta variant

The UK Health Security Agency (UKHSA) has published an updated risk assessment for the Omicron variant, that suggests this new form of the SARS-CoV-2 virus is displaying a significant growth advantage over Delta, meaning that it is likely to outcompete Delta in the UK and become the dominant variant.

The assessment is based on analysis of UK data showing increased household transmission risk, increased secondary attack rates - that is the chance of each case infecting another individual - and increased growth rates compared to Delta.

If the growth rate and doubling time continue at the rate seen in the last two weeks since the existence of Omicron was first announced by scientists in South Africa, it is expected at least 50% of COVID-19 cases to be caused by the Omicron variant in the next 2-4 weeks. The UK recorded 51,342 cases of COVID-19 on Wednesday 8 December.

The risk assessment also suggests that Omicron reduces the level of protection given by having had a previous infection or vaccination. Whilst there are insufficient data to quantify either vaccine effectiveness or risk of reinfection in the UK exactly, the observed growth, case distribution and early analyses in both South Africa and the UK are consistent with some loss of immune protection against infection. UKHSA said new studies are being undertaken to assess this further.

As yet, there are insufficient data to make any assessment of protection against severe disease, or to assess the severity of illness caused by Omicron. Further studies are underway in the UK and abroad.

One of the reasons for the gap in the data is that only half of the PCR tests are able to detect Omicron. This gap is being filled by sending 15 – 20% of all PCR tests samples for genomic sequencing.

UKHSA’s chief medical advisor, Susan Hopkins said, “It is increasingly evident that Omicron is highly infectious and there is emerging laboratory and early clinical evidence to suggest that both vaccine-acquired and naturally acquired immunity against infection is reduced for this variant.”

Since the emergence of SARS-CoV-2 virus and its global spread, the UK has sequenced and shared more than 1.4 million genomes. It has been gradually increasing sequencing capacity since March 2021 with the weekly upload of sequences increasing from 20,000 genomes per week to 64,000 last week and it will be closer to 80,000 by January 2022.

Pfizer and BioNTech say Omicron variant reduces the efficacy of their vaccine

While preliminary laboratory studies demonstrate that three doses of the Pfizer/BioNTech COVID-19 vaccine can neutralise the Omicron variant, the initial two dose schedule shows significantly reduced neutralisation, the two companies said this week.

However, two doses may still induce protection against severe disease.

The companies are working on a variant-specific vaccine for Omicron and expect to have it available by March. If such a modification is required that will not impact the ability to manufacture four billion doses in 2022

The data, released on December 8, are the results from an initial laboratory study. They show blood samples from individuals who had received two doses of the current COVID-19 vaccine exhibited, on average, more than a 25-fold reduction in neutralising antibodies against the Omicron variant compared to wild-type that first emerged in Wuhan, and against which the vaccine was designed.

More robust protection may be achieved by a third dose, as data from additional studies indicate that a booster increases the antibody levels by 25-fold. According to the companies’ preliminary data, a third dose provides a similar level of neutralising antibodies to Omicron as is observed after two doses against wild-type and other variants that emerged before Omicron.

GSK says its antibody is effective against new Omicron variant of SARS-CoV-2

GlaxoSmithKline said Xevudy, its monoclonal antibody for treating COVID-19, has been shown to retain full activity in lab tests against the Omicron variant of SARS-CoV-2.

The data was generated through pseudo-virus testing of all the 37 mutations seen in Omicron, which are raising concern that the variant will be resistant to vaccines and antiviral drugs.

These findings build on the initial preclinical data published last week, showing Xevudy retained in vitro activity against key individual mutations of the Omicron variant, and add to the growing body of preclinical evidence demonstrating that Xevudy retains activity against all tested variants of concern.

Hal Barron, chief scientific officer of GSK said that from the outset it was hypothesised that Xevudy would have a high barrier to resistance. “These pre-clinical data demonstrate the potential for our monoclonal antibody to be effective against the latest variant, Omicron, plus all other variants of concern defined to date by the World Health Organisation, and we look forward to discussing these results with regulatory authorities around the world,” Barron said.

The European Medicines Agency is currently reviewing GSK’s application for marketing approval of Xevudy, which binds to a part of SARS-CoV-2 which is shared with its relative SARS-CoV-1. That indicates that the epitope is highly conserved, which may make it more difficult for resistance to develop.

Wellcome awards grant for development of novel COVID-19 antiviral drug

Japanese pharmaceutical company Sosei announced its UK subsidiary Sosei Heptares has received a grant from the research charity Wellcome Trust to advance the preclinical development of oral antiviral drug targeting the main protease of SARS-CoV-2, an enzyme critical to replication of the virus, as a potential treatment for COVID-19.

Sosei Heptares initiated its COVID-19 R&D programme in April 2020, applying its structure-based drug design capabilities to selectively inhibit the protease. The most advanced candidate resulting from this research, SH-879, has demonstrated potent anti-viral activity against SARS-CoV-2 and potential for oral dosing, with a differentiated profile from other anti-viral drugs for COVID-19 that are either approved or in late stage development.

Work on SH-879 will now be accelerated with the support of the Wellcome grant, made through the COVID-19 Therapeutics Accelerator. The Accelerator was launched in March 2020 by Wellcome, Bill & Melinda Gates Foundation and Mastercard, to speed the development of COVID-19 therapeutics that address gaps in existing treatment research.

EMA starts rolling review of Valneva’s COVID-19 vaccine

The European Medicines Agency said it has decided to start a rolling review of the French biotech Valneva’s COVID-19 vaccine, based on preliminary results from laboratory studies and early clinical studies in adults.

These studies suggest the vaccine triggers the production of antibodies that target SARS-CoV-2, EMA said.

The vaccine contains inactivated SARS-CoV-2 virus that cannot cause the disease, along with two adjuvants that are intended to strengthen the immune response to the vaccine.

Bavarian Nordic says its COVID-19 vaccine could be universal booster

Danish vaccines manufacturer Bavarian Nordic announced positive topline results from a phase II clinical trial of its COVID-19 vaccine candidate, ABNCoV2, showing it has potential to be used as a booster to other types of COVID-19 vaccines.

A total of 103 participants who had been previously vaccinated with mRNA or adenoviral COVID-19 vaccines were enrolled and received a single booster vaccination with ABNCoV2. At enrollment, around 57% either had no detectable neutralising antibodies and/or were below the levels that could be quantified, or were at levels reported to provide decreased levels of protection from COVID-19.

One week post vaccination with ABNCoV2, a 2-34-fold increase in the levels of neutralising antibodies against the Wuhan SARS-CoV2 variant was observed and peaked at two weeks with a 2-40-fold increase depending on the initial antibody levels.

However, all subjects, irrespective of whether they initially had very low, or high levels of neutralising antibodies were boosted to absolute antibody levels reported to be associated with a very high efficacy against COVID-19.

The same trend in terms of the fold-increases post the booster with ABNCoV2 was also observed for the Alpha, Beta and Delta variants.

Paul Chaplin, CEO of Copenhagen-based Bavarian Nordic, said the results confirm ABNCoV2 has, “the perfect profile” for a universal booster vaccine.

Commission calls for concerted effort to block the Omicron variant

The EU and member states should implement a joint strategy to limit the entry of the Omicron variant into the EU, with daily reviews of essential travel restrictions, and be ready to impose all necessary controls, the Commission said in a statement calling for a coordinated approach to dealing with the resurgence of COVID-19.

There is a rapidly rising number of infections across Europe caused by the Delta variant of SARS-CoV-2, which is putting renewed pressure on hospitals. The new potential threat from the Omicron variant is adding to these concerns, the Commission said.

“Over the last couple of weeks, many of us have witnessed it first hand: COVID 19 has resurged,” said Ursula von der Leyen, president of the European Commission. On top of this, the arrival of the “presumably highly contagious” Omicron variant calls for “our utmost attention,” she said.

Member states need to step up vaccination and investment in treatments and improve monitoring and prevention.

Stella Kyriakides, commissioner for health said the high transmissibility of the Delta variant, the high number of people who are not vaccinated, and the easing of control measures such as social distancing and mask wearing “will bring us a challenging winter.”

“The emergence of the Omicron variant only adds to the urgent need to vaccinate and to boost our immunity in order to break transmission chains,” Kyriakides said.

The Commission said it will step up efforts to manufacture, authorise and jointly procure COVID-19 therapeutics.

COVID-19 pushes UNESCO framework on open science over the line

“The COVID-19 pandemic has brought into focus how open science practices such as open access to scientific publications, the sharing of scientific data and collaboration beyond the scientific community can speed up research and strengthen the links between science policy and society,” said Audrey Azoulay, UNESCO director general, unveiling the first global definition of open science.

The framework, which has been adopted by 193 countries, will make science more transparent and more accessible, equitable and inclusive, allowing scientists and engineers use open licenses to share their publications and data, software and even hardware more widely.

That will enhance international scientific cooperation, Azoulay said. “The UNESCO Recommendation on Open Science will drive the wider adoption of open practices, encourage greater endorsement of open science and ensure that research findings are beneficial to all.”

While currently some 70% of scientific publications are locked behind paywalls, over the past two years, this proportion has dropped to about 30% for publications on COVID-19, showing science can be more open.

Before the UNESCO framework, there was no universal definition of open science, with standards set only at regional, national or institutional levels. In adopting the framework, the 193 countries have agreed to abide by common standards and adopted a common roadmap. The signatories will report back every four years on their progress.

Rise in number of Omicron cases found in Europe

The European Centre for Disease Control said that as of 1 December 2021, 15 additional cases of the Omicron variant of concern have been confirmed, bringing the total to 59 confirmed cases.

The cases have been reported across Europe, in Austria (3), Belgium (2), Czechia (1), Denmark (4), France (1, in Réunion), Germany (9), Italy (4), the Netherlands (16), Portugal (14), Spain (2), and Sweden (3).

A number of probable cases have also been reported from across the region, but are still under investigation. All cases for which there is available information on severity were either asymptomatic or mild and it remains the case that to date, there have been no severe infections and no deaths reported.

UK approves GSK’s antibody treatment for COVID-19 infections

The UK Medicines and Healthcare products Regulatory Agency has approved the use of Xevudy, an antibody developed by GlaxoSmithKline, for people with mild to moderate COVID-19, who are at high risk of developing severe disease.

This is the second monoclonal antibody therapeutic to be approved in the UK, following Ronapreve.

The European Medicines Agency began its review of Xevudy on 18 November, when it said, “it could deliver an opinion within two months.” The agency previously approved Ronapreve, developed by Roche, along with another monoclonal antibody Regkirona, developed by the South Korean biotech Celltrion, for COVID-19.

Xevudy works by binding to the spike protein on the outside of the COVID-19 virus, preventing the virus from attaching to and entering human cells, so that it cannot replicate in the body.

In a clinical trial, a single dose of the intravenously administered antibody was found to reduce the risk of hospitalisation and death by 79% in high-risk adults with symptomatic COVID-19 infection. Risk factors include diabetes, heart disease and age over 60. The drug is most effective when taken during the early stages of infection and it should be used as soon as possible, and within five days of symptom onset.

MHRA said it is too early to know whether the Omicron variant has any impact on Xevudy’s effectiveness, but it will work with GSK to establish this.

UK approves GSK’s antibody treatment for COVID-19 infections

This is the second monoclonal antibody therapeutic to be approved in the UK, following Ronapreve.

Xevudy works by binding to the spike protein on the outside of the COVID-19 virus, preventing the virus from attaching to and entering human cells, so that it cannot replicate in the body.

MHRA said it is too early to know whether the Omicron variant has any impact on Xevudy’s effectiveness, but it will work with GSK to establish this.

ECDC confirms 33 cases of new Omicron variant have been picked up in the EU

As of 29 November 2021, 33 confirmed cases of the Omicron variant of concern have been reported in Austria, Belgium, Czechia, Denmark, Germany, Italy, Netherlands and Portugal, according to the European Centre for Disease Control and Surveillance (ECDC).

A number of probable cases have also been reported that are still under investigation. All confirmed cases have a history of travel to African countries, with some having taken connecting flights at airports between Africa and Europe.

Separately, Scotland’s health minister Humza Yousaf said six cases reported in Scotland were not all related to travel, indicating there may be some community transmission.

ECDC said for those cases for which there is information available severity was either asymptomatic or mild. No severe cases and no deaths have been reported among Omicron cases so far.

J&J working to assess if new Omicron variant reduces effectiveness of its COVID-19 vaccine

In collaboration with academic groups in South Africa and around the world, Johnson & Johnson is now evaluating the effectiveness of its COVID-19 vaccine against the new and rapidly spreading Omicron variant, testing blood serum from participants in completed and ongoing booster studies to look for neutralising activity against the variant.

At the same time, the company said it is working on an Omicron-specific variant vaccine, which it will advance as needed.

Omicron highlights the importance of continued surveillance, testing and vaccination to prevent hospitalisation and deaths from COVID-19, said Mathai Mammen, global head of Janssen Research & Development at Johnson & Johnson. “We will not be complacent. Building on our long-term collaboration with scientists on the ground in South Africa and the ongoing real world effectiveness studies being conducted with the Johnson & Johnson COVID-19 vaccine, we will work together to generate new data on Omicron.”

“In parallel, we have begun work to design and develop a new vaccine against Omicron and will rapidly progress it into clinical studies if needed,” Mammen said.

ECDC raises alarm about Omicron variant of SARS-CoV-2 virus

There is considerable uncertainty related to the transmissibility, vaccine effectiveness, risk for reinfections and other properties of the Omicron variant of SARS-CoV-2, the European Centre for Disease Control said in its assessment of the threat of the new variant.

However, given its immune escape potential and potentially increased transmissibility advantage compared to Delta, “We assess the probability of further introduction and community spread in [Europe] as ‘high’,” CDC said.

With the number of COVID-19 infections caused by the Delta variant already on the rise in Europe before the emergence of Omicron was announced by South Africa’s Ministry of Health on Friday 26 November, the impact of the introduction and possible further spread of Omicron could be ‘very high’, ECDC added.

Based on the mutation profile of Omicron, partial immune escape is likely, and genomic surveillance remains of utmost importance for early detection of the presence of this variant, to enable the following of epidemiological trends and guide containment measures.

Following on from the announcement of the emergence of the new variant, its naming and designation by the World Health Organization as a variant of concern, cases have been reported from across Europe and in Canada.

Moderna announces strategy to deal with Omicron SARS-CoV-2 variant

Moderna said it is testing three existing COVID-19 vaccine booster candidates against the Omicron variant and also developing a new variant-specific vaccine candidate against the SARS-CoV-2 variant of concern that was first identified in South Africa.

Omicron includes mutations seen in the Delta variant that are believed to increase transmissibility, and mutations seen in the Beta and Delta variants that are believed to promote immune escape, making vaccines less effective. The combination of mutations represents a significant potential risk of the waning of natural and vaccine-induced immunity and a booster dose of an authorised vaccine represents the only currently available strategy for boosting waning immunity.

Moderna is working to test the ability of the current vaccine dose to neutralise the Omicron variant and data is expected in the coming weeks. The company has also tested a higher dose booster in healthy adults and has completed dosing of 306 participants in a safety and immunogenicity study of this high dose.

In addition, Moderna is studying two multi-valent booster candidates in the clinic, that are designed to anticipate mutations such as those that have emerged in the Omicron variant. The first candidate includes several mutations present in Omicron that are also present in the Beta variant, while the second includes many of the mutations present in Omicron that also occur in both the Beta and Delta variants.

Now Moderna will rapidly advance an Omicron-specific booster candidate and says it has demonstrated the ability to advance new candidates to clinical testing in 60-90 days.

“The mutations in the Omicron variant are concerning and for several days we have been moving as fast as possible to execute our strategy to address this variant,” said Stéphane Bancel, CEO of Moderna. “We have three lines of defence that we are advancing in parallel: we have already evaluated a higher dose booster of mRNA-1273; second, we are already studying two multi-valent booster candidates in the clinic that were designed to anticipate mutations such as those that have emerged in the Omicron variant and data is expected in the coming weeks; and third, we are rapidly advancing a Omicron-specific booster candidate,” he said.

Study finds there is a gradual increase in COVID-19 infection risk after 2nd vaccine dose

The protection two doses of the Pfizer/BioNTech vaccine provide from COVID-19 infection wanes with time, suggesting a third booster dose might be necessary, according to an Israeli study published in the British Medical Journal.

Israel was one of the first countries to roll out a large scale COVID-19 vaccination campaign in December 2020, but has seen a resurgence of infections since June 2021.

The research, carried out by the Research Institute of Leumit Health Services in Tel Aviv, confirms that the Pfizer-BioNTech vaccine provided excellent protection in the initial weeks after vaccination, but suggests that protection wanes for some individuals with time.

Examining the time elapsed since vaccination and risk of infection is needed to inform decisions about the need for a third injection, and its preferred timing.

The researchers examined electronic health records of 80,057 adults who had a PCR test for COVID-19 at least three weeks after their second injection. Of these 80,057 participants, 7,973 (9.6%) had a positive test result. These individuals were then matched to negative controls of the same age and ethnic group who were tested in the same week.

The rate of positive results increased with time elapsed since a second dose. Across all age groups 1.3% of participants tested positive 21-89 days after a second dose, but this increased to 2.4% after 90-119 days; 4.6% after 120-149 days; 10.3% after 150-179 days; and 15.5% after 180 days or more.

After taking account of other potentially influential factors, the researchers found a significantly increased risk of infection with time elapsed since a second dose.

Compared with the initial 90 days after a second dose, the risk of infection across all age groups was 2.37-fold higher after 90-119 days; 2.66-fold higher after 120-149 days; 2.82-fold higher after 150-179 days; and 2.82-fold higher after 180 days or more.

The researchers say they cannot rule out the possibility that other unmeasured factors, such as household size, population density, or virus strain may have had an effect. However, this was a large study of people who all received the same vaccine, and they were able to carry out detailed analysis of the data, suggesting the results are robust.

They conclude that in individuals who received two doses of the Pfizer/BioNTech vaccine, protection decreased over time, and the risk of breakthrough infection increased progressively compared with the protection provided during the initial 90 days.

The results suggest booster doses are warranted, the researchers say.

COVID-19 became more lethal in late 2020, but Alpha variant not entirely to blame

A new statistical analysis suggests that COVID-19 became more lethal in the UK in late 2020, but points to multiple factors, and not just the rise of the more infectious Alpha variant of the virus first identified in Kent, that were to blame.

Studying how the lethality of COVID-19 has changed over time in different regions could help guide efforts to address this disease. While preliminary evaluations of infection and mortality data suggest that COVID-19 may have become more lethal in the UK in late 2020, more rigorous analyses have been lacking.

To explore this further, Patrick Pietzonka and colleagues at the Department of Applied Mathematics and Theoretical Physics, Cambridge University, used Bayesian inference, a technique that enabled them to draw statistically stronger conclusions about lethality from weekly data on the number of cases and the number of deaths due to COVID-19 in the UK.

Specifically, the researchers compared predictions from different mathematical simulations of COVID-19 spread and deaths, some of which incorporated increased lethality.

The analysis suggests that in late autumn of 2020 COVID-19 did indeed become more lethal in the UK, meaning that the probability that an infected person would die from the disease increased.

It was thought this increase in lethality was driven by the Alpha variant of the SARS-CoV-2 virus, which was more infectious than previous variants.

However, the new analysis suggests that lethality increased to a greater degree than the Alpha variant would have accounted for, and that the increase in lethality began before Alpha became widespread.

These findings suggest that, while the Alpha variant contributed to increased lethality in late 2020, other factors were also in play.

Further research will be needed to identify those factors, but Pietzonka and colleagues suggest they may include both the increased strain on healthcare services and the seasonal cycle in the severity of viruses that is seen in other respiratory diseases like the common cold and flu.

French researchers find more evidence SARS-CoV-2 went from bats to humans

Scientists in the Department of Virology at the Institut Pasteur in Paris have identified coronaviruses closely related to SARS-CoV-2 from two bats sampled in Cambodia more than a decade ago.

The discovery, described in Nature Communications, along with the recent detection of the closest ancestors of SARS-CoV-2 known to date in cave-dwelling bats in Laos, indicates that SARS-CoV-2-related viruses that cause COVID-19 have a much wider geographic distribution than previously reported, and further supports the hypothesis that the pandemic originated via spillover of a bat-borne virus.

The researchers used metagenomic sequencing to identify the nearly identical viruses in two horseshoe bats, Rhinolophus shameli, originally sampled in 2010. The findings suggest that SARS-CoV-2 related viruses are likely circulate via multiple Rhinolophus species.

The limited understanding of the geographic distribution of SARS-CoV possibly reflects a lack of sampling in southeast Asia, or at least across the Greater Mekong subregion, which encompasses Myanmar, Laos, Thailand, Cambodia, Vietnam, and the Yunnan and Guanxi provinces of China, the researchers say.

In addition to bats, the researchers note that pangolins and certain species of cat, civet, and weasels found in this region are readily susceptible to SARS-CoV-2 infection, and might represent intermediary hosts for transmission to humans.

These findings underscore the importance of increasing surveillance of pathogens in wildlife in southeast Asia, which hosts a high diversity of wildlife and where trade in wildlife puts humans in direct contact with wild hosts of SARS-like coronaviruses.

EMA begins review of oral COVID-19 antiviral drug

The European Medicines Agency has started evaluating an application for approval of the oral antiviral drug Lagevrio, developed by Merck Sharp & Dohme.

The agency said it will assess the drug under a reduced timeline and could issue an opinion within weeks, because it has already reviewed a substantial portion of the data in a rolling review.

These data include interim results from the main study on the effects of Lagevrio in non-hospitalised, unvaccinated patients with at least one underlying condition putting them at risk of severe COVID-19. The hope is that having an oral treatment people can take at home will reduce the severity of infection and avoid the need for admission to hospital.

Lagevrio reduces the ability of SARS-CoV-2 virus to multiply in the body by introducing mutations in the genetic material of SARS-CoV-2 during replication.

EMA previously issued advice to member states on use of Lagevrio in advance of formal approval on 19 November 2021.

In other COVID-19 regulatory news, EMA recommended granting an extension of indication for Pfizer/BioNTech’s COVID-19 vaccine, to include use in children aged 5 to 11. The vaccine is already approved for use in children aged 12 and above.

Swiss scientists find previous infection with other coronaviruses protects against SAR-CoV-19

A team of researchers led by the University of Zurich has discovered previous antibody responses to other, harmless, coronaviruses contributes to SARS-CoV-2 immunity.

“People who have had strong immune responses to other human coronaviruses also have some protection against SARS-CoV-2 infection,” said Alexandra Trkola, head of the Institute of Medical Virology at the university.

In their study, the researchers used a specially developed assay to analyse antibody levels against four other human coronaviruses in 825 blood samples taken before SARS-CoV-2 emerged. They also examined 389 samples from donors infected with SARS-CoV-2.

Combining these analyses with computer-based models enabled the team to precisely predict how well the antibodies would bind to and neutralise invading viruses.

The researchers demonstrated that people who caught SARS-CoV-2 had lower levels of antibodies against coronaviruses that cause common colds, compared to uninfected people. In addition, people with high levels of antibodies against harmless coronaviruses were less likely to have been hospitalised after catching SARS-CoV-2.

“Our study shows that a strong antibody response to human coronaviruses increases the level of antibodies against SARS-CoV-2. So someone who has gained immunity to harmless coronaviruses is therefore also better protected against severe SARS-CoV-2 infections,” says Trkola.

This type of immune response, referred to as cross-reactivity, also occurs with T cell responses, the second line of defense against infections.

“Even though the protection isn’t absolute, cross-reactive immune responses shorten the infection and reduce its severity. And this is exactly what is also achieved through vaccination, just much, much more efficiently,” said Trkola.

It is not yet known whether this cross-reactivity also works in the opposite direction and if immunity to SARS-CoV-2 achieved through vaccination also offers protection against other human coronaviruses.

Latest data shows Pfizer/BioNTech COVID-19 vaccine works in 12 – 15 year olds

New data on the Pfizer/BioNTech vaccine shows it has 100% efficacy against COVID-19 in adolescents aged 12 - 15, with no serious safety concerns identified, paving the way for the companies to apply for approval in this age group.

The adverse event profile was generally consistent with other clinical safety data for the vaccine, with no serious safety concerns observed in individuals with at least 6 months of safety follow-up after the second dose.

“These additional data provide further confidence in our vaccine’s safety and effectiveness profile in adolescents. This is especially important as we see rates of COVID-19 climbing in this age group in some regions, while vaccine uptake has slowed,” said Albert Bourla, CEO of Pfizer.

Results from this analysis of 2,228 trial participants build upon and confirm previously released data and demonstrate strong protection against COVID-19. From the 30 confirmed symptomatic cases of COVID-19 in the trial with and without evidence of prior infection with SARS-CoV-2, 30 cases of COVID-19 were in the placebo group and 0 cases were in the Pfizer/BioNTech vaccine group.

With infections rising across Europe, EMA starts evaluating booster dose of Johnson & Johnson’s single shot COVID-19 vaccine

The European Medicines Agency has started evaluating an application for the use of a booster dose of COVID-19 Vaccine Janssen to be given at least two months after the first dose to people aged 18 years and older.

The agency’s human medicines committee will carry out an accelerated assessment of data, including results from more than 14,000 adults who received a second dose of the COVID-19 vaccine Janssen or placebo two months after the initial dose.

The outcome of this evaluation is expected within weeks.

Extended telework due to COVID-19 gets a thumbs up, but there is fear of social isolation

A survey of 3,821 Flemish employees, representative for gender, age and education level, who were surveyed end March 2020, showed a large majority (65.9%) were satisfied with the increase in teleworking during the pandemic, according to researchers at the University of Ghent.

Almost half of the employees doing more teleworking said it is beneficial for stress (45.7%) and burnout prevention (42.7%), and on-the-job concentration (44.7%). In addition, more than half (55.7%) feel that homeworking has had a positive effect on their work-life balance.

The main problem is social isolation, with two-thirds of respondents reporting a weaker bond with their colleagues (64.0%), and more than half feeling less connected with their employer (56.0%).

“Notwithstanding the exceptional time of sudden, obligatory and high-intensity telework, Flemish employees in general mainly attribute positive characteristics to telework, such as a better work-life balance and increased concentration,” said researcher Eline Moens.

Whether telework is seen as positive or negative differs from employee to employee and from job to job.

The personal context was important as well: gender, age, whether you have children or not, turns out to be important for the evaluation of telework.

Overall, the experience of teleworking during the pandemic led to an increased desire do more teleworking in the future (62.7%).

“The question is to what extent employees will be able to force these aspirations regarding more telework in the workplace after the pandemic. In our opinion, how employers have experienced the extended telework will be decisive in this respect,” said researcher Stijn Baert

Pandemic leads to big drop in the use of antibiotics in Europe

New data from the European Centre for Disease Prevention and Control (ECDC) show that antibiotic consumption decreased by more than 18% between 2019 and 2020.

This is the largest annual decrease in the two decades of reporting via the European Surveillance of Antimicrobial Consumption Network. The decrease was observed in 26 of the 27 reporting countries of the EU and European Economic Area. The changes were largest and most consistent in the primary care sector, and are most likely a result of the COVID-19 pandemic, according to ECDC.

From 2016 and 2019 there was decrease in the population-weighted mean annual change in the consumption of antibacterials of 1.8%. Between 2019 and 2020, the decrease was ten times higher, at 18.3%.

One explanation for the decrease is a general drop in the number of primary care consultations during the COVID-19 pandemic, with people more cautious about seeking healthcare for mild or self-limiting infections, or due to difficulties in getting medical appointments.

Another is that the large decrease in prescribing of antibiotics commonly used to treat respiratory tract infections reflects the reported low incidence of non-COVID-19-related respiratory tract infections. This has been attributed to measures put in place as a response to the pandemic, including physical distancing, face masks and promotion of hand hygiene.

Prior to the COVID-19 pandemic, the primary care sector accounted for about 80% to 90% of all antibiotic prescriptions, mainly for respiratory tract infections.

ECDC said it remains to be seen if the decline in antibiotic consumption observed in 2020 will be sustained throughout 2021, and what implications the decrease may have on antimicrobial resistance in Europe overall.

EMA starts evaluating another COVID-19 vaccine

The European Medicines Agency has begun the formal review of US biotech Novavax’s COVID-19 vaccine, Nuvaxovid, saying the assessment will proceed under an accelerated timeline, and the outcome could be known within weeks.

The short timeframe is possible because EMA has already reviewed a substantial portion of the data on the vaccine during a rolling review, looking at preclinical data, manufacturing and data on the vaccine’s safety, immunogenicity and efficacy against COVID-19 from clinical studies.

"Novavax looks forward to providing an additional vaccine option in Europe, built on a proven, well-understood technology platform,” said Stanley Erck, CEO of Novavax.

Nuvaxovid has been evaluated in two phase III trials: a trial in the U.K. that demonstrated efficacy of 96.4% against the original virus strain, 86.3% against the Alpha variant and 89.7% efficacy overall; and a trial in the US and Mexico that demonstrated 100% protection against moderate and severe disease and 90.4% efficacy overall.

The vaccine is engineered from the genetic sequence of the first strain of SARS-CoV-2 virus that causes COVID-19.

New research underlines the dire effect the pandemic had on arts and culture

Researchers at Sheffield University have measured the economic impact of COVID-19 on the UK’s arts, culture and heritage sector, showing that nationally output fell dramatically as COVID-19 hit in March 2020.

There was a decline of around one third between the second quarter of 2019 and the same three months in 2020, in real terms. The creative, arts and entertainment sub-sector, and the libraries, archives, museums and other cultural activities sub-sector, were the worst hit, with declines of 63% and 45% respectively.

For the sector as a whole, gross value added fell by around 20% (real change, constant prices), compared to around 10% for the UK economy overall.

The dramatic falls in output mask some significant variations between sub-sectors ranging from an estimated plus 17% to minus 70%.

Activities that grew, or were only subject to modest declines (+17% to -5% range) in output, included computer games, software, educational book publishing, TV broadcasting and libraries.

Activities very badly affected (-30% to -70% range) included cinema, performing arts, museums and historical sites.

Air pollution increases the severity of COVID-19 infections

Long-term exposure to air pollution is associated with a higher risk of developing COVID-19 among those people who get infected, shows a study led by the Barcelona Institute of Global Health (ISGlobal).

A series of studies have indicated that regions with higher pre-pandemic levels of air pollution had a higher incidence of COVID-19 cases and deaths. However, the reasons for this association are not yet clear; air pollution could favour airborne transmission of the virus, or it could increase an individual’s susceptibility to infection or disease.

“The problem is that previous studies were based on reported cases, which had been diagnosed, but missed all the asymptomatic or undiagnosed cases,” said Manolis Kogevinas, ISGlobal researcher and first author of the study.

The research team combined technology for measuring a series of virus-specific antibodies in a cohort of adults living in Catalonia, with information on the long-term exposure of such individuals to air pollutants.

The study included 9,605 participants among which there were 481 confirmed cases (5%). In addition, blood samples from over 4,000 participants were taken to determine the presence and quantity of antibodies to five viral antigens. Of these, 18% had virus-specific antibodies, but no association was found between infection and exposure to air pollutants.

However, among those who got infected, an association was found between higher exposure to air pollution and higher levels of antibodies. There was also an association between higher exposure to air pollution and disease symptoms, particularly for severe cases that ended in the hospital or in intensive care.

“Our study provides the strongest evidence globally on the association of ambient air pollution and COVID-19,” said Kogevinas. “These results are in line with the association between air pollution and hospitalisation described for other respiratory diseases such as influenza or pneumonia.”

Air pollution could also contribute by promoting the development of cardiovascular, respiratory or other chronic conditions, which in turn increase the risk of severe COVID-19.

EMA gives green light to first monoclonal antibodies treatments for COVID-19

The European Medicines Agency has recommended approval of two monoclonal antibody drugs, Ronapreve and Regkirona for treating COVID-19.

The drugs can now be used in patients aged 12 years of age on older who do not require oxygen, but are at increased risk of their disease becoming severe.

Whilst conducting its review, EMA gave advice to member states on the use of the two therapies, which means they are already available in some countries.

The antibodies are designed to attach to the spike protein of SARS-CoV-2, via which the virus enters human cells. That preferential attachment blocks the virus’ route into cells in the respiratory tract.

EMA evaluated data from studies showing that treatment with Ronapreve or Regkirona significantly reduces hospitalisation and deaths in COVID-19 patients at risk of severe COVID-19.

Another study showed that Ronapreve reduces the chance of contracting COVID-19 if a household member is infected.

Overall 0.9% of patients treated with Ronapreve, 11 of 1,192 in the study, were hospitalised or died within 29 days of treatment. That compared with 3.4% of patients on placebo (40 out of 1,193 patients).

Ronapreve was also found to be effective at preventing symptoms in infected people. Amongst the people who tested positive for SARS-CoV-2 after contact, 29% of people (29 out of 100) who received Ronapreve developed symptoms compared with 42.3% of people (44 out of 104) who received a placebo.

A main study in patients with COVID-19 showed that Regkirona treatment led to fewer patients requiring hospitalisation or oxygen therapy or dying, when compared with placebo.

Among the patients at increased risk of their illness becoming severe, 3.1% of patients treated with Regkirona (14 out 446) were hospitalised, required supplemental oxygen or died within 28 days of treatment, compared with 11.1% of patients on placebo (48 out of 434).

The European Commission has agreed a contract for 55,000 courses of Ronapreve with its manufacturer, Swiss pharma Roche.

Pfizer strikes deal to allow generics companies to manufacture its new COVID-19 antiviral drug

Pfizer and the UN-backed Medicines Patent Pool (MPP), announced the signing of a voluntary license agreement for Pfizer’s COVID-19 oral antiviral drug Paxlovid, which has been shown to cut the risk of hospitalisation or death by 89%.

The agreement will enable MPP to support additional production and distribution of the drug by granting sub-licenses to generic medicine manufacturers, with the goal of providing greater access for low and middle income countries.

Under the terms of the license agreement qualified generic medicine manufacturers worldwide that are granted sub-licenses will be able to supply Paxlovid to 95 countries, covering up to 53% of the world’s population.

This includes all low- and lower-middle-income countries and some upper-middle-income countries in sub-Saharan Africa. Pfizer will not receive royalties on sales in low-income countries and will waive royalties on sales in all countries covered by the agreement while COVID-19 remains classified as a public health emergency of international concern by the World Health Organisation.

“Pfizer remains committed to bringing forth scientific breakthroughs to help end this pandemic for all people. We believe oral antiviral treatments can play a vital role in reducing the severity of COVID-19 infections, decreasing the strain on our healthcare systems and saving lives,” said Albert Bourla, Pfizer CEO. “We must work to ensure that all people, regardless of where they live or their circumstances, have access to these breakthroughs, and we are pleased to be able to work with MPP to further our commitment to equity.”

Charles Gore, Executive Director of MPP said, “[Paxlovid] is to be taken together with ritonavir, an HIV medicine we know well, as we have had a license on it for many years, and we will be working with generic companies to ensure there is enough supply for both COVID-19 and HIV.”

The global health agency Unitaid created MPP ten years ago “for this exact purpose”, to secure licenses that enable and accelerate access to affordable quality treatments for people in resource-limited settings, said Philippe Duneton, Executive Director of Unitaid. “This agreement could help us to reach more people more quickly as soon as the medicine is approved and, when coupled with increased access to testing, bring benefits to millions.”

MPP is inviting expressions of interest from generics manufacturers based anywhere in the world for sublicences to manufacture and sell co-packs of Paxlovid and ritonavir.

New research could pave the way for COVID-19 vaccines that provide longer lasting immunity

Scientists at University College London say that by designing next generation vaccines for COVID-19 to activate immune memory T cells, it may be possible to eliminate SARS-CoV-2 at the very start of an infection, thereby helping stop its spread.

The suggestion is based on research published in Nature today, describing how intensive monitoring of healthcare workers in London from before the pandemic took hold in March 2020, showed that despite their high risk, 58 participants did not test positive for COVID-19 at any point.

Analysis of their blood showed they had increased levels of memory T cells that reacted against SARS-CoV-2. These T cells target infected cells expressing replication proteins which the virus needs to spread once it enters a human host cell.

The proteins are common to all coronaviruses and remain highly conserved. Unlike the spike protein targeted by first generation vaccines, these are unlikely to change or mutate.

Leo Swadling, Medical Research Foundation Research Fellow at UCL and lead author, said it was known that some individuals remain uninfected despite having likely exposure to the virus.

“What we didn’t know is whether these individuals really did manage to completely avoid the virus, or whether they naturally cleared the virus before it was detectable by routine tests,” Swadling said. “By intensively monitoring health care workers for signs of infection and immune responses, we identified a minority with this particular SARS-CoV-2 specific T cell response.”

A vaccine that can induce T cells to recognise and target infected cells expressing replication proteins would be more effective at eliminating early SARS-CoV-2, and may have the added benefit of being active against other coronaviruses.

European Commission buys 60M doses of Valneva’s COVID-19 vaccine

The European Commission has approved its eighth COVID-19 vaccines contract, signing a deal for French biotech Valneva to supply 27 million doses in 2022, and a further 33 million in 2023.

The contract includes the intention to adapt the vaccine to new variant strains of SARS-CoV-2, should that be necessary. With the product yet to be approved by the European Medicines Agency, initial supplies are expected in April 2022.

The agreement is a huge boost for the company, after the UK government cancelled a $1.65 billion contract to buy the vaccine in mid-September.

The vaccine uses traditional technology, in which a whole virus is inactivated. It is hoped that this might persuade people who were reluctant to receive vaccines based on novel mRNA and viral vector platforms, to get vaccinated.

While it is based on the original strain of SARS-CoV-2 that emerged in in Wuhan, in the phase III trial in the UK, the vaccine was effective in preventing severe disease at a time when the Delta variant was dominant.

None of the trial participants who contracted the infection was so seriously ill that they had to be admitted to hospital.

President of the European Commission, Ursula von der Leyen, said, “The contract allows for the vaccine to be adapted to new variants. Our broad portfolio will help us to fight COVID and its variants in Europe and beyond. The pandemic is not over. Everyone who can, should get vaccinated.”

Thomas Lingelbach, CEO of Valneva, said, “Our phase III results confirmed the advantages often associated with inactivated vaccines and we continue to believe that our differentiated vaccine candidate could make an important contribution to the global fight against the COVID-19 pandemic.”

Fall in antibiotic use during pandemic hints at inappropriate prescribing in more normal times

Antibiotic Research UK released new research on antibiotic prescribing in England during the first 12 months of the pandemic, showing there was a 17% reduction in the prescribing of antibiotics in general practice compared to the previous year.

Analysis of the data also reveals that the rise in antibiotic prescribing that occurs each winter, from December to February, compared to the summer, from June to August, was considerably lower at 4%, compared to the rise seen in the winter of 2019 to 2020, before the pandemic began, when it was 21%.

This study highlights the potential of sustaining lower antibiotic prescribing rates in general practice, according to Colin Garner chief executive of Antibiotic Research UK, a charity which is working to address the rise of antimicrobial resistance.

“Although typical cough symptoms can take up to three weeks to resolve, we also know that antibiotics for most respiratory tract infections - your typical cough, sore throat, earache - do not speed up recovery times. Instead, they often give patients many side effects, and promote the development of resistant bacteria,” Garner said.

The dramatic fall in antibiotic prescribing during the COVID-19 pandemic could be due to many factors, including less infection transmission during lockdowns and fewer visits to GPs. More work is needed to understand the extent to which each of these factors has resulted in this drop in antibiotic prescribing.

But, Garner said, “The data does tell us that antibiotic prescribing can be reduced to help protect us all from the danger of the growing threat of antibiotic resistance.”

EMA speeds up review of Merck COVID-19 antiviral following UK approval

The European Medicines Agency (EMA) and the heads of Europe’s national drug regulators have agreed to expedite the review of Merck’s antiviral pill for treating COVID-19, after the UK approved the drug last week.

The context for speeding up the review of molnupiravir is the need for additional guidance on COVID-19 treatments in light of rising rates of infection and deaths due to COVID-19 across the EU.

This will help national authorities in decisions on whether to use the antiviral prior to its authorisation.

While the EMA’s more comprehensive rolling review is ongoing ahead of a possible application for marketing approval, this will provide EU-wide recommendations in the shortest possible timeframe.

Molnupiravir is an oral antiviral medicine that reduces the ability of SARS-CoV-2 to multiply in the body, by increasing the number of mutations in the virus in a way that impairs its ability to replicate.

Emer Cooke, EMA executive director, requested the expedited review following discussions with EMA’s COVID-19 pandemic task force, which brings together experts from across the European medicines regulatory network.

SARS-CoV-2 variant detected in dogs and cats with suspected myocarditis

A new study in the journal Veterinary Record shows that pets can be infected with the alpha variant of SARS-CoV-2, which was first detected in Kent, UK, last December.

The study describes the first identification of the SARS-CoV-2 alpha variant in domestic pets; two cats and one dog were positive on PCR testing, while two additional cats and one dog displayed antibodies two to six weeks after they developed signs of cardiac disease. Many owners of these pets had developed respiratory symptoms several weeks before their pets became ill and had also tested positive for COVID-19.

All of these pets had an acute onset of cardiac disease, including severe myocarditis, an inflammation of the heart muscle.

“Our study reports the first cases of cats and dogs affected by the COVID-19 alpha variant and highlights, more than ever, the risk that companion animals can become infected with SARS-CoV-2,” said lead author Luca Ferasin, of the Ralph Veterinary Referral Centre, in the UK.

“We also reported the atypical clinical manifestations characterised by severe heart abnormalities, which is a well-recognised complication in people affected by COVID-19, but has never described in pets before. However, COVID-19 infection in pets remains a relatively rare condition and, based on our observations, it seems that the transmission occurs from humans to pets, rather than vice versa.”

Meanwhile, researchers in the US have shown that 40% of white deer from animals sampled across the country tested positive for SARS-CoV-2, and conclude the infection passed from humans to deer and is now being transmitted deer-to-deer.

Evidence of transmission of SARS-CoV-2 from human to animals and then spreading among animals is of concern because of the potential for an increased number of mutations promoting the development of more virulent variants.

The possibility exists that new animal reservoirs of SARS-CoV-2 could emerge, each with unique potential to maintain, disseminate, and drive novel evolution of the virus. Of particular concern are wildlife species that are both abundant and live in close association with humans

Birmingham University outlicenses anti-viral nasal spray against COVID-19

Birmingham University has signed a licensing agreement to commercialise a novel anti-viral nasal spray that protects against COVID-19.

COVID-19 is both contracted and transmitted by inhalation of droplets or aerosols containing the SARS-CoV-2 virus, and the nose is the major viral entry point into the body. The anti-viral spray is designed to work by encapsulating and deactivating the virus while it is still in the nose, preventing its wider uptake by the body.

It is formulated with two compounds that are already approved by regulatory bodies in the UK, Europe and the US, and widely used in drugs and food products.

The first is a polysaccharide gel which is retained on the mucous-coated epithelia in the nose where it coats and retains the virus, so the virus does not travel further down the respiratory tract. The second compound, carrageenan, is a potent antiviral agent.

Researchers in Birmingham have confirmed the complete inhibition of SARS-CoV-2 activity by carrageenan and the ability of the formulation to prevent contraction and transmission in cell culture.

They also confirmed that the spray covers a surface area that is six times greater than when formulated without the gel.

The formulation, engineered by Liam Grover, from the university’s Healthcare Technologies Institute, has been licensed to the company Birmingham Biotech for commercialisation. “As COVID-19 restrictions around the world are gradually lifting, there is a real need for effective methods of viral protection. While existing measures like wearing masks and handwashing remain essential, this nasal spray provides an additional protective measure with the potential to reduce transmission,” Grover said.

Pandemic pause over, carbon emissions are poised to bounce back

Worldwide carbon emissions in 2021 are set to rebound to close to pre-COVID levels, according to the 16th edition of the Global Carbon Project.

COVID-19 lockdowns caused fossil carbon emissions to drop by 5.4% in 2020, but the new report projects an increase of 4.9% this year, to 36.4 billion tonnes.

Emissions from coal and gas will grow more in 2021 than they fell in 2020, but emissions from oil use remain below 2019 levels.

For major emitters, 2021 emissions appear to be returning to the pre-COVID trends of decreasing CO2 emissions for the US and EU, and increasing CO2 emissions for India. For China, the response to the COVID-19 pandemic has sparked further growth in CO2 emissions, pushed by the power and industry sectors.

The researchers say a further rise in emissions in 2022 cannot be ruled out if road transport and aviation return to pre-pandemic levels and coal use is stable.

"The rapid rebound in emissions as economies recover from the pandemic reinforces the need for immediate global action on climate change," said Pierre Friedlingstein of Exeter University’s Global Systems Institute, who led the study.

"The rebound in global fossil CO2 emissions in 2021 reflects a return towards the pre-COVID fossil-based economy. Investments in the green economy in post-pandemic recovery plans of some countries have been insufficient so far, on their own, to avoid a substantial return close to pre-COVID emissions," Friedlingstein said.

UK is first to approve oral antiviral drug against COVID-19 that can be taken at home

The UK Medicines and Healthcare products Agency has become the first to approve Merck and Co’s oral antiviral drug Lagevrio, after concluding it reduces the risk of hospitalisation and death in people with mild to moderate COVID-19 who are at increased risk of developing severe disease.

Lagevrio works by preventing the SARS-CoV-2 virus from replicating, keeping virus levels low in the body and reducing the severity of the disease. It is most effective when taken during the early stages of infection and so the recommendation is to use it as soon as possible following a positive COVID-19 test, and within five days of symptoms onset.

The approval is for treating people who have mild to moderate COVID-19 and at least one risk factor for developing severe illness, such as obesity, older age (>60 years), diabetes or heart disease.

June Raine, MHRA Chief Executive said Lagevrio is the first antiviral for COVID-19 that can be taken by mouth rather than administered intravenously. “This is important, because it means it can be administered outside of a hospital setting, before COVID-19 has progressed to a severe stage,” she said.

Merck’s application to the US Food and Drug Administration for Emergency Use Authorisation of Lagevrio is under review, while the European Medicines Agency has started a rolling review of the marketing authorisation application.

The US government has agreed to purchase 1.7 million courses of treatment, while the UK has placed an initial order for 480,000, which will be used in a real world trial designed to gather further data on the effectiveness of Lagevrio.

Brightest ever X-ray shows up COVID-19 lung damage

The damage caused by COVID-19 to the lungs’ smallest blood vessels has been intricately imaged by scientists from the European Synchrotron Research Facility and University College London (UCL), using high-energy X-rays emitted by a newly updated particle accelerator.

The new imaging technology, Hierarchical Phase Contrast Tomography (HiP-CT), enables 3D mapping across a range of scales, allowing clinicians to view the whole organ as never before by imaging it as a whole and then zooming down to cellular level.

The technique relies on X-rays generated by the European Synchrotron particle accelerator in Grenoble, France, which following a recent upgrade, now provides the brightest source of X-rays in the world, at 100 billion times brighter than a hospital X-ray.

The enables the imaging of blood vessels down to five microns in diameter, a tenth of the diameter of a hair, in an intact human lung. In comparison a clinical grade CT scan only resolves blood vessels that are about 100 times larger, around 1mm in diameter.

Using HiP-CT, the research team in the UK, France and Germany, have seen how severe COVID-19 infection shunts blood between the two separate systems in the lungs, moving it from the capillaries which oxygenate the blood, to those which feed the lung tissue itself. Such cross-linking stops the patient’s blood from being properly oxygenated, a finding which was previously hypothesised but not proven.

Claire Walsh of UCL’s Department of Mechanical Engineering said the ability to see organs across scales like this will “really be revolutionary” for medical imaging. “As we start to link our HiP-CT images to clinical images through artificial intelligence techniques, we will for the first time be able to highly accurately validate ambiguous findings in clinical images,” she said.

Italian researchers show Pfizer/BioNTech COVID-19 vaccine induces long-lived memory T cell response

Pfizer/BioNTech’s mRNA vaccine for COVID-19 induces a sustained and fully functional memory T cell immune response for up to six months after the second dose, according to a new study of 71 healthcare workers and scientists in Italy who received the vaccine.

The research by Gisella Guerrera and colleagues at the Santa Lucia Foundation in Rome, indicates the vaccine offers long-lived immunity against SARS-CoV-2, creating a persistent reservoir of potent cells specifically targeted to the virus.

The research published in Science this week found that vaccination induced an anti-viral memory T cell response that included both CD4+ and CD8+ stem memory cells that can perform multiple immune functions, from spurring cytokine production to stimulate the immune system, to interacting with B cells to promote antibody production.

It is far harder to measure T cells than antibodies, meaning antibody levels are looked to in assessing waning immune responses. The researchers suggest that with more than 90% of the vaccinated study subjects developing T cells with these lasting protective features, their findings could have implications for discussions about the use of third “booster” doses of the vaccine.

Novavax completes submission of its COVID-19 vaccine to EMA, as Indonesia becomes the first country to approve it

US biotech Novavax announced it completed the rolling submission of data on its COVID-19 vaccine to the European Medicines Agency (EMA) and the Canadian regulator Health Canada, as the vaccine received its first approval from the regulator in Indonesia.

The product, NVX-CoV2373, is the only protein-based vaccine to have gained an approval.

In a Brazil/US clinical trial it was over 100% effective in preventing serious infections, and 90.4% effective overall.

In a phase III trial involving 15,000 participants in the UK, the vaccine demonstrated efficacy of 96.4% against the original virus strain, 86.3% against the Alpha variant and 89.7% efficacy overall.

Novavax has a manufacturing partnership with the Serum Institute of India, the world's largest supplier of COVID-19 vaccines.

“This is a landmark moment for Novavax and our partner, Serum Institute of India, and it is the first of many authorisations that Novavax expects in the coming weeks and months for our vaccine globally,” said Stanley Erck, Novavax CEO.

The vaccine was engineered from the genetic sequence of the first strain of SARS-CoV-2, using Novavax's recombinant nanoparticle technology to generate antigen derived from the coronavirus spike protein.

It will be packaged as a ready-to-use liquid formulation in a vial containing ten doses, and can be stored in conventional refrigerators, meaning it is possible to distribute it through existing vaccine supply channels, potentially increasing access in hard-to-reach areas of Indonesia and other countries with low COVID-19 vaccination rates.

"Access to supply of a safe and highly effective vaccine, coupled with the ease of its distribution, should be a critical enabler to help Indonesia control the current coronavirus outbreak," said Adar Poonawalla, CEO of the Serum Institute of India.

French researchers show chatbot can bust COVID-19 vaccine hesitancy

Vaccine hesitancy is one of the major challenges in containing the COVID-19 pandemic and previous studies have revealed that mass communication, through television and radio adverts, is not a very effective means of persuading the hesitant.

It is known that having the chance to discuss your particular concerns with an expert whom you trust can be more persuasive, but having a face-to-face talk with every vaccine-hesitant individual is impractical.

To overcome this problem, a team of cognitive scientists from the Institut Jean-Nicod and the Laboratoire de Neurosciences Cognitives et Computationnelles created a chatbot that provides users with answers to 51 common questions about COVID-19 vaccines.

Chatbots have the advantage of offering quick, personalised Q and A sessions while reaching a large number of people.

The team tested their chatbot with 338 individuals and compared their reactions to those of a control group of 305 participants who read a brief paragraph that gave information about COVID-19 vaccines.

After a few minutes of interaction with the chatbot, the number of participants with positive views of vaccination increased by 37%. People were also more open to getting vaccinated after using the chatbot: declarations of vaccine refusal fell 20%. Such changes in attitude were negligible in the control group.

It remains to be seen whether the effects of chatbot interaction are lasting, and whether they are the same across age groups, and among those most resistant to vaccination.

Nevertheless, the study demonstrated that a chatbot can indirectly reach a very large audience: half of the experimental group later tried to persuade others to get vaccinated, with three-quarters of them stating they drew on information provided by the chatbot to do so.

Clinical trial shows depression drug is effective in treating COVID-19

The results of a new randomised clinical trial, published in The Lancet Global Health, have demonstrated that using the depression treatment fluvoxamine to treat high-risk outpatients with early-diagnosed COVID-19 reduces the need for prolonged observation in an emergency setting or hospitalisation, compared to a control group who received a placebo.

The results represent an important step in understanding the role of fluvoxamine for outpatients with early diagnosed, symptomatic COVID-19 and reinforce the concept that it is possible to generate rapid and high-quality evidence during the pandemic.

“Recent vaccination developments and campaigns have proved to be effective and important in reducing the number of new symptomatic cases, hospitalisations, and deaths due to COVID-19. However, COVID-19 still poses a risk to individuals in countries with low resources and limited access to vaccinations,” said Edward Mills of McMaster University, Canada, co-principal investigator on the trial.

“Identifying inexpensive, widely available, and effective therapies against COVID-19 is therefore of great importance, and repurposing existing medications that are widely available and have well-understood safety profiles is of particular interest.” Mills said.

Fluvoxamine is a selective serotonin reuptake inhibitor used to treat mental health conditions such as depression and obsessive-compulsive disorders. It was chosen for study as a potential treatment for COVID-19 due to its anti-inflammatory properties.

The trial began in June 2020 with the fluvoxamine arm beginning in January 2021, recruiting a cohort of Brazilian adults who were symptomatic, had tested positive for COVID-19, were unvaccinated, and had at least one additional criterion for high risk.

A total of 741 participants were given 100mg of fluvoxamine twice daily for ten days and 756 participants received a placebo. The trial participants were observed for 28 days post-treatment, with the main outcome of the trial being patients spending more than six hours receiving physician treatment at a specialised COVID-19 emergency setting, or hospitalisation.

Of the 741 participants who received fluvoxamine, 79 (10.6%) required an extended stay for more than six hours in an emergency setting or hospitalisation, compared to 119 (15.7%) of participants who received the placebo. These results demonstrated an absolute reduction in the risk of prolonged hospitalisation/prolonged emergency care of 5% with a relative risk reduction of 32%.

Anglo-German research shows synthetic version of vitamin B1 blocks replication of SARS-CoV-2

An Anglo-German team of researchers has identified a potential new treatment that suppresses the replication of SARS-CoV-2, after showing that cells infected with virus can only generate more viruses when a particular metabolic pathway is activated.

A synthetic version of vitamin B1, which is a known inhibitor of this pentose phosphate pathway, blocked SARS-CoV-2 replication and the virus could not replicate in infected cells.

The research, by scientists at the University of Kent and Goethe-University Frankfurt, found synthetic vitamin B1 also increased the antiviral activity of another drug. This shows that pentose phosphate pathway inhibitors are a potential new treatment option for COVID-19, both on their own and in combination with other treatments.

In addition, the mechanism differs from that of other antiviral COVID-19 drugs, and viruses resistant to these may be sensitive synthetic vitamin B1.

Martin Michaelis, professor of molecular medicine at Kent University said, “This is a breakthrough in the research of COVID-19 treatments. Since resistance development is a big problem in the treatment of viral diseases, having therapies that use different targets is very important and provides further hope for developing the most effective treatments for COVID-19.”

Co-researcher, Jindrich Cinatl of the Institute for Medical Virology at Goethe-University Frankfurt, said, “Targeting virus-induced changes in the host cell metabolism is an attractive way to interfere specifically with the virus replication process.”

Research indicates 2020 UK government scheme to boost the economy drove second wave of COVID-19 infections

A large-scale government subsidy aimed at encouraging people to eat out in restaurants in the wake of the first 2020 COVID-19 wave in the UK, accelerated a second COVID-19 wave, according to new research.

The COVID-19 pandemic hurt economies around the world, with the hospitality sector particularly vulnerable, due to the decline in tourism and leisure activities.

This rippled across economies, as hospitality workers then reduce their spending and had trouble meeting basic expenses. Some governments used fiscal policy to help the hospitality sector by stimulating demand. One example is the UK Eat-Out-To-Help-Out scheme, which had the inadvertent effect of promoting COVID-19 infections, according to research by Thiemo Fetzer of the Department of Economics at Warwick University.

The scheme, designed to encourage demand for hospitality and restaurants, directly subsidised the cost of meals and non-alcoholic drinks by up to 50% in participating restaurants across the UK for meals served on all Mondays to Wednesdays from 3 August to 31 August 2020.

The discount was capped at a maximum of £10 per person, but there was no limit on how often people could benefit. Aggregate data suggest that the government subsidised 160 million meals, costing the taxpayer £849 million. Restaurant visits increased dramatically on Monday to Wednesday. Official government statistics released at the end of January 2021 suggest that at least 59,981 businesses registered for the scheme.

Areas with higher participation in the Eat-Out-To-Help-Out scheme saw both a notable increase in new COVID-19 infection clusters within a week of the scheme starting, and a deceleration in infections within two weeks of the scheme ending.

Areas that had notable rainfall during the prime lunch and dinner hours on days the scheme was active, making customers less likely to visit restaurants to take advantage of the subsidised meals, had a lower infection rate.

The empirical estimates suggest that the scheme may have been responsible for around 11% of all new detected COVID-19 clusters emerging during August and into early September in the UK.

Spanish study provides robust evidence that COVID-19 is a seasonal infection

A key question about SARS-CoV-2 is whether it is behaving, or will behave, as a seasonal virus like influenza, or whether it will be equally transmitted during any time of the year.

Now, a new study led by the Barcelona Institute for Global Health (ISGlobal), has provided evidence that COVID-19 is a seasonal infection linked to low temperatures and humidity, much like flu.

The results, published in Nature Computational Science, also highlight the considerable contribution of airborne SARS-CoV-2 transmission to the spread of infection and the need to promote air hygiene measures.

“The question of whether COVID-19 is a genuine seasonal disease becomes increasingly central, with implications for determining effective intervention measures,” said Xavier Rodó, director of the Climate and Health programme at ISGlobal and coordinator of the study.

Rodó and colleagues first analysed the association of temperature and humidity in the initial phase of SARS-CoV-2 spread in 162 countries across five continents, before changes in human behaviour and public health policies were put into place. The results show a negative relationship between the transmission rate (R0) and both temperature and humidity at the global scale: higher transmission rates were associated with lower temperatures and humidity.

The researchers then analysed how this association between climate and disease evolved over time, and whether it was consistent at different geographical scales, using a statistical method that was specifically developed to identify similar patterns of variation at different windows of time.

Again, they found a strong negative association for short time windows between disease, in terms of number of cases and climate, with reference to temperature and humidity. There were consistent patterns during the first, second and third waves of the pandemic at different spatial scales: worldwide, at country level, down to individual regions within highly affected countries, where they looked at Lombardy, Thüringen and Catalonia, and even to the city level in the case of Barcelona.

The first epidemic waves waned as temperature and humidity rose, and the second wave rose as temperatures and humidity fell. However, this pattern was broken during summertime in all continents. “This could be explained by several factors, including mass gatherings of young people, tourism, and air conditioning, among others,” said Alejandro Fontal, first author of the study.

Applying the model in the southern hemisphere, where the virus arrived later, the same negative correlation was observed.

Finally, using an epidemiological model, the researchers showed that incorporating temperature into the transmission rate works better for predicting the rise and fall of the different waves, particularly the first and third ones in Europe. “Altogether, our findings support the view of COVID-19 as a true seasonal low-temperature infection, similar to influenza and to the more benign circulating coronaviruses,” said Rodó.

The research also highlights the need to include meteorological parameters in the evaluation and planning of control measures.

EMA says Moderna COVID-19 vaccine suitable for use as booster

EMA’s human medicines committee has said a booster dose of Moderna’s COVID-19 vaccine Spikevax may be considered in people aged 18 years and above, after reviewing data showing a third dose given 6 to 8 months after the second dose led to a rise in antibody levels in adults whose antibody levels were waning.

The booster dose consists of half the dose used for the primary vaccination schedule.

Current data indicate the pattern of side effects after the booster is similar to what occurs after the second dose. The risk of inflammatory heart conditions or other very rare side effects after a booster is being carefully monitored, EMA said.

EMA does not dictate vaccines policy at a national level, but its approval means public health bodies may issue official recommendations on the use of booster doses, taking into account the local epidemiological situation, as well as new effectiveness data and the fact there is limited safety data for the booster dose.

Earlier in October EMA concluded that a booster dose of Pfizer/BioNTech’s vaccine may be considered at least six months after the second dose for people aged 18 years and older.

Commission names ten drugs for treating COVID-19

The Commission has established a portfolio of ten potential COVID-19 treatments and says it will expedite access to the drugs across Europe, once they are approved.

The list includes possible treatments for COVID-19 that are in the process of being authorised and which should therefore soon be available on the European market.

While vaccination against COVID-19 offers the best protection against infection, the Commission says at the same time it is ensuring that the appropriate treatments are available for those who are infected.

“We have already signed four joint procurement contracts for different treatments related to COVID-19 and we are ready to negotiate more. Our aim is to allow at least three treatments in the coming weeks, and possibly two more by the end of the year, and to help member states to access them as soon as possible,” said Stella Kyriakides, health commissioner.

The list was drawn up by a group of independent scientific experts who examined 82 drugs at an advanced stage of clinical development, taking into account the different types of product needed for different patient populations and at varying stages, and degrees of severity of the disease.

This list of ten treatments includes three categories and will continue to evolve as new scientific data becomes available:

1. Antiviral monoclonal antibodies, most effective in the early stages of infection:

Ronapreve, a combination of two monoclonal antibodies casirivimab and imdevimab, from Regeneron Pharmaceuticals and Roche

Xevudy (sotrovimab), from Vir Biotechnology and GlaxoSmithKline

Evusheld, a combination of the two monoclonal antibodies tixagevimab and cilgavimab, from AstraZeneca

2. Oral antivirals to be used as soon as possible after infection:

Molnupiravir, from Ridgeback Biotherapeutics and Merck Sharp Dome

PF-07321332, from Pfizer

AT-527 from Atea Pharmaceuticals and Roche

3. Immunomodulators for the treatment of hospital patients:

Actemra (tocilizumab), by Roche

Kineret (anakinra) by Swedish Orphan Biovitrum

Olumiant (baricitinib), Eli Lilly

Lenzilumab, by Humanigen

Pandemic fallout prompts call for urgent action on health research data in Germany

The COVID-19 pandemic made visible the poor state of health data research in Germany. While urgent issues regarding the transmission dynamics of the virus, interaction with other health conditions, and recording and assessment of reactions to vaccines, were being intensively studied and answers being found in other European countries, in Germany this is only happening with delays, requires great effort - or is even entirely impossible.

Against this backdrop, the Interdisciplinary Commission for Pandemic Research of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) has now issued a statement, in which it calls for data for health-related research to be made more accessible and more linkable.

The Commission points out that research in Germany is not only suffering from a lack of data and methodological underpinnings, but that much needed progress in health-related research is blocked, as access to existing data is often inadequate and that linking such data is associated with significant organisational and legal obstacles.

In its statement, the Commission highlights five fields of action that are interconnected factually and temporally, and should be addressed jointly.

Development of a system of consent for legally compliant and trust-based use of data is required as a first step. In addition, electronic patient records should be developed further to feature an opt-out approach for consent to data collection. National disease registers or epidemiological registers should be established and expanded to avoid incomplete data analysis and duplicates, detect gaps and harness linkage potential. It must also be ensured that these registers are searchable and can be linked to other data sources.

The Commission also says that data should be consolidated and that a sustainably funded central data integration body should be established. This body should function as a trust agency that is legally and organisationally able to grant access to data and to link different sets of data.

Gender gap revealed in academic journal submissions during first COVID-19 wave

The onset of pandemic may have amplified existing gender inequalities in academia, according to an analysis of data on over five million academic authors by Flaminio Squazzoni and colleagues at the University of Milan.

The study of 2,329 academic journals found that during the first wave of the COVID-19 pandemic fewer manuscripts were submitted by women than men, and that this gender gap was especially prominent in the medical research and for women in earlier stages of their careers.

While the onset of the COVID-19 pandemic prompted unusually high numbers of submissions of academic articles, lockdown policies forced academics to handle new family responsibilities, potentially exacerbating known family-related challenges for women in academia. Previous studies have examined this possibility, but the findings have been inconsistent.

Squazzoni and colleagues applied statistical analyses to submission data from 2,329 journals published by Elsevier. They also examined data on academics who were invited to review submissions as part of the peer-review process. In total, data on over five million authors working between February 2018 and May 2020 was analysed.

Between February and May of 2020, submissions to Elsevier journals increased by 30% compared to the same period in 2019. However, women submitted fewer manuscripts than men across academic fields including medicine, life sciences, physical sciences, and social sciences. This gender gap was especially strong in health and medicine, the field that is most directly related to COVID-19, and for women towards the beginning of their careers.

Meanwhile, for most academic fields, similar proportions of women and men accepted invitations to review manuscripts. However, this was not the case for health and medicine, in which women were less involved.

Overall, these findings suggest that the onset of the pandemic may have fostered an environment that was relatively advantageous for men in academia. Given the importance of publishing for academic career success, the gender deficits observed in this study could potentially have long-term effects that deepen gender inequality in academia.

Scientists show plasma technology can safely clean disposable PPE for reuse

Scientists at Southampton University have developed a new method to safely clean and reuse facemask respirators using low-temperature plasma technology.

They say the method could help in future pandemics by providing contingency options should a shortage of personal protective equipment (PPE) for frontline healthcare staff occur again.

The study showed that the technology can remove 99.99% of coronavirus from contaminated facemasks, while maintaining their ability to filter out harmful airborne droplets.

The technique could reduce by approximately 70% the plastic waste caused by facemasks.

Min Kwan Kim, lecturer in astronautics , who led the research said, “Although most of the masks are considered one-time use, the reuse of masks may need to be considered as a crisis capacity strategy.”

Other techniques to decontaminate PPE have been trialled, including hydrogen peroxide, ultraviolet irradiation, and moist heat. However, these can negatively affect mask performance, either by damaging the filters or leaving residues that are harmful to skin.

The research team applied microdroplets containing SARS-CoV-2 to FFP2 and FFP3 facemasks, the most commonly used by frontline healthcare staff. A prototype decontamination system was then used to apply cold plasma to the samples for two, five and ten minutes. They then tested the samples for the presence of residual SARS-CoV-2 and transmitted aerosols of sodium chloride through the samples to monitor filter performance.

The results showed that the samples that were treated for ten minutes had been successfully decontaminated and the researchers found no significant impact on the filters for both the FFP2 and FFP3 masks.

Pfizer says booster dose of its COVID-19 vaccine is highly effective

Pfizer and its partner BioNTech announced topline results from a phase III trial evaluating the efficacy and safety of a booster dose of their COVID-19 vaccine in more than 10,000 individuals 16 years of age and older.

In the trial, a booster dose administered to individuals who previously received the primary two doses restored protection against COVID-19 to the high levels achieved after the second dose, showing a relative vaccine efficacy of 95.6% when compared to those who did not receive a booster. These are the first efficacy results from any randomised, controlled COVID-19 vaccine booster trial.

“We look forward to sharing these data with health authorities and working together to determine how they can be used to support the rollout of booster doses around the world,” said Albert Bourla, CEO of Pfizer.

During the study, there were five cases of COVID-19 in the booster group, and 109 cases in the non-booster group. The adverse event profile was generally consistent with other clinical safety data for the vaccine, with no safety concerns identified.

The companies said they plan to share these data with the US Food and Drug Administration, European Medicines Agency, and other regulatory agencies as soon as possible.

In the US a booster dose is authorised for emergency use in people 65 years of age and older. Booster doses of the vaccine are approved in the EU, with recommendations for population subgroups varying based on local health authority guidance.

Canadian researchers show how cultural differences shape responses to COVID-19

A Canadian study exploring cross-cultural differences in knowledge and attitudes towards COVID-19 shows that people in Europe had the least knowledge of COVID-19 and the lowest tendency to care about the coronavirus, while people in the US had the lowest tendency to comply with public health restrictions.

As the pandemic began to unfold, people in the Middle East and Asia were the most aware of COVID-19. People in the Middle East were also the most afraid of the coronavirus.

The study was led by researchers at McGill University who conducted a survey of 1,296 participants in 8 different countries over 5 continents in April 2020. The aim was to measure whether age, gender, education, and occupational status had an impact on knowledge of the coronavirus.

Knowledge of COVID-19 was higher among females overall, particularly in regions like Oceania Africa, the Middle East, Europe, and South Asia. However, in north America, knowledge of COVID-19 was higher among males.

The researchers note the COVID-19 death toll was highest in the US and in Europe compared to other regions and suggest that perhaps with more awareness of COVID-19 in advance, the damage could have been reduced.

Effective pandemic management requires support from the general population to combat the spread of the disease and previous studies of contagious disease outbreaks, like the H1N1 flu, have shown that improved knowledge increases the uptake of preventive measures and influences protective behaviour at the individual and community level.

Despite the severe COVID-19 situation in Europe, researchers found that in April 2020 only 35.5% of people wore a mask. This rate was significantly lower compared to the overall mask wearing rate of 78.1%.

Karolinska research shows two vaccine doses boost antibody levels in the airways after COVID-19

Antibodies in the airways quickly wane after SARS-CoV-2 infection, but vaccination results in a strong increase in antibody levels, especially after two doses, according to a new study from Karolinska Institutet.

The results suggest that having a second dose of vaccine after recovering from COVID-19 may be important for protecting against re-infection and to prevent transmission.

“What makes the study unique is that we have looked at samples from both blood and airways, which has given us new knowledge of the local immune response where the virus infects,” said Anna Smed-Sörensen, research group leader at the Department of Medicine, Solna, Karolinska Institutet. “Since it is more difficult to sample the airways, we know much less about antibody levels there than in the blood.”

The researchers examined how the levels and durability of antibodies to SARS-CoV-2 differed between individuals who had mild to severe COVID-19. 147 patients were recruited in March to May 2020 and monitored for up to eight months after infection. In 20 of the patients, they also studied antibody levels after vaccination and compared the results with a control group that had not previously had COVID-19.

Their results show that individuals who had more severe COVID-19 infections had higher antibody levels upon recovery, compared to individuals with mild disease. The antibodies in the blood remained at measurable levels for at least eight months, while those in the airways were short-lived and disappeared after three months.

“The positive news is that the antibodies quickly returned after vaccination in those who previously had COVID-19, not only in the blood but also in the airways,” said Smed-Sörensen. “We found that the antibody levels in the airways after two doses of vaccine were often even higher than they were during the course of the disease. People who had not had COVID-19 before vaccination had much lower or undetectable levels.”

“Our results demonstrate that to only study blood does not reflect the antibody levels in the respiratory tract, which likely play a major part in neutralising the virus locally,” said Karin Loré, professor in the Department of Medicine. “Completing the vaccination with a second dose may therefore be important for achieving optimal immune responses and reducing the spread of infection between individuals.”

The level of antibodies required for protection against infection remains unknown, as well as whether the rapid drop in antibody levels in the airways allows for re-infection. The researchers will now continue to analyse samples from additional longitudinal time points and examine the inflammatory environment in the respiratory tract during infection, convalescence and after vaccination.

French biotech Valneva in line for approval of COVID-19 vaccine

Valneva said it is moving to submit its COVID-19 vaccine for approval by the UK regulator MHRA and to the European Medicines Agency, after reporting positive results in a phase III trial.

The vaccine, VLA 2001, successfully met two primary endpoints, generating higher levels of neutralising antibodies than AstraZeneca’s approved vaccine, against which it was compared, and with more than 95% of participants developing antibodies against the SARS-CoV-2 virus.

In addition, VLA2001 was well tolerated, with fewer side effects reported than with the AstraZeneca vaccine.

The trial was designed to show the immune response generated by VLA2001 is non-inferior to that generated by AstraZeneca’s vaccine; it was not able to assess how effective VLA2001 is in preventing infection. There were cases of infection in participants who received VLA2001, but none required hospital admission.

The occurrence of COVID-19 cases was similar between both vaccines. Valneva said the complete absence of any severe COVID-19 cases suggests that both vaccines can prevent severe COVID-19.

VLA2001 is based on traditional inactivated virus vaccine technology. Thomas Lingelbach, CEO of Valneva, said, “These results confirm the advantages often associated with inactivated whole virus vaccines. We are committed to bringing our differentiated vaccine candidate to licensure as quickly as possible and continue to believe that we will be able to make an important contribution to the global fight against the COVID-19 pandemic.”

The results are “both impressive and extremely encouraging,” said Adam Finn, professor of paediatrics at Bristol University, who was principal investigator for the trial. “This is a much more traditional approach to vaccine manufacture than the vaccines so far deployed in the UK, Europe and north America and these results suggest this vaccine candidate is on track to play an important role in overcoming the pandemic,” Finn said.

EU issues report on implementation of digital COVID-19 passports

The Commission issued a report on the EU digital COVID certificate and its implementation across the EU, showing that the certificate has been a crucial element in Europe's response to the pandemic, with more than 591 million certificates generated.

The EU says it has set a global standard and is currently the only system in operation at international level. At present 43 countries across four continents are plugged into the system, and more will follow over the coming weeks and months.

Twenty member states also use the EU Digital COVID Certificate for domestic purposes, such as for the access to large events and restaurants, cinemas and museums, with an additional national legal basis.

The certificate, which covers COVID-19 vaccination, test and recovery, facilitates safe travel and has been key to support Europe's hard-hit tourism industry, the report says.

Commissioner for Internal Market, Thierry Breton said, “The EU system is adopted by countries around the world, demonstrating how Europe can set global standards through decisive and coordinated action.”

New manufacturing sites and new formulation approved for Pfizer/BioNTech COVID-19 vaccine

The European Medicines Agency has approved two additional manufacturing sites for the production of Pfizer/BioNTech’s COVID-19 vaccine in Italy.

Following the approval, the two sites will be operational immediately and will produce up to 85 million additional doses to supply the EU in 2021.

At the same time, EMA has approved a ready-to-use formulation of the vaccine, with much easier handling requirements than the original version. The new formulation does not require dilution prior to administration, will be available in a 10-vial pack size containing 60 doses, and can be stored at 2-8°C for up to 10 weeks

The current concentrated formulation requires dilution prior to administration, is available in a 195-vial, 1,170 dose, pack size and can be stored at 2-8°C for one month only.

The improvements will provide better storage, transport and logistic options for vaccine distribution and administration. The new formulation will be available in a phased rollout starting in early 2022.

EMA also announced it has started evaluating an application to extend the use of BioNTech/Pfizer’s COVID-19 vaccine to children aged 5 to 11.

German biotech CureVac stops development of COVID-19 vaccine

Curevac has withdrawn its COVID-19 vaccine from the approval process at the European Medicines Agency, after ditching it in favour or a second generation product.

The company said recent communication with EMA indicated the earliest approval date was the second quarter of 2022 and by this time, it expects the second generation vaccine programme, being advanced in partnership with GlaxoSmithKline, will have progressed to late stage clinical development.

The decision is also reflects the evolving dynamics of the pandemic response towards a greater need for differentiated vaccines to address the fact that SARS-CoV-2 is becoming endemic. As a result, the existing advanced purchase agreement with the European Commission, which was predicated on employing the first generation vaccine to address the acute pandemic need, will cease.

CureVac is assessing the possibility of leveraging existing commitments for the second generation vaccine.

CureVac and GSK have tightened their collaboration by adding further resources and experts to accelerate development and manufacturing of the broad second generation programme. The companies anticipate entering clinical development in the next months, aiming to achieve regulatory approval for an improved COVID-19 vaccine in 2022.

“We remain committed to making a difference with a safe and efficacious vaccine. This goal has not changed, but the requirements to effectively address the virus and emerging variants have changed,” said Franz-Werner Haas, CEO of CureVac.

EMA said it has been looking at data on the Curevac vaccine since February 2021, as part of a rolling review, whereby the company submits data as they become available in order to speed up the evaluation of an eventual marketing authorisation application.

The agency said it had raised some questions about the vaccine’s quality, impacting the benefit-risk balance of the vaccine, and the fact that results of the main clinical study showed only a modest vaccine efficacy in adults. These issues “still remained to be satisfactorily addressed,” EMA said.

The vaccine was only 47% effective in preventing COVID-19 infections in the 40,000-person phase III study.

Scientists suffer pandemic levels of abuse

A survey of 321 scientists who have spoken to the media about COVID-19, many of whom had also commented on social media about the pandemic, has found that 15% experienced death threats and 22% received threats of physical or sexual violence.

The survey, carried out by the journal Nature, found that more than a quarter of the respondents said they ‘always’ or ‘usually’ received comments from trolls or personal attacks after speaking about COVID-19. More than 40% experienced emotional or psychological distress.

Respondents who reported most frequently being trolled online or receiving personal attacks were also most likely to say that their experiences had greatly affected their willingness to speak to the media in the future. Some anonymous respondents wrote that they were hesitant to speak about some topics because they saw the abuse received by others.

However, scientists generally appreciated their interactions with media despite their other experiences: overall, 85% of researchers rated their experiences with the media during the pandemic as ‘always’ or ‘mostly’ positive; 84% said they were able to get their message out to the public; and 63% said speaking to the media was personally rewarding.

Michael Head, senior research fellow in global health at Southampton University, said, “I myself have received plenty of abuse throughout the pandemic. For those of us who have been pulling apart anti-vaccine misinformation from pre-pandemic times, the presence of these attempts at intimidation is very wearying, but not surprising.

He added, “In my view, the intensity of such harassment has gone up significantly across the pandemic, including becoming more organised and frightening than simply mindless comments on social media.”

The misinformation spread around Europe and North America also has far-reaching consequences in terms of inducing vaccine hesitancy further afield, Head said.

Population level study in France demonstrates effectiveness of COVID-19 vaccines in the real world

A large scale French study has confirmed the effectiveness of three COVID-19 vaccines, with real world data showing the risk of being admitted to hospital with severe disease was cut by over 90% at 14 days after the second dose.

The research, carried out by the government health data research body Epi-Phare, used information on 22.6 million people aged 50 to 74, and 7.2 million aged over 75.

In each cohort half were vaccinated, with either the Pfizer/BioNTech, Moderna or AstraZeneca vaccines, and half were not.

Among those vaccinated aged 50 to 74 years, just over 53% had received Pfizer vaccine, 7.1% Moderna and 39.2% AstraZeneca. Among those aged 75 years and older, just over 85% had received Pfizer, 8.7% Moderna, and 6.1% AstraZeneca.

Epi-Phare says the results are very consistent, highlighting the significant effectiveness of the three vaccines, with reduction in the risk of hospitalisation from the 14th day after the injection of the second dose greater than 90% in both age groups, for each vaccine. The reduction in the risk of death was also cut by 90%.

The effectiveness of vaccination against severe forms of Covid-19 did not appear to wane over the follow-up period of up to 5 months.

To examine the impact of the Delta variant, the reduction in the risk of hospitalisation for COVID-19 was estimated during the start of circulation of the Delta variant in France, between 20 June and 20 July 2021. Over this period, efficacy was 84% in the cohort aged 75 and over and 92% in the cohort aged 50 to 74. The researchers say that although based on a short period, this provides the first evidence on the effect of the Delta variant on risk reduction.

There will be continued monitoring to measure the evolution of efficacy over a longer period and to better characterise the impact of the Delta variant.

Swedish study shows COVID-19 vaccination reduces transmission in high risk environments

People without immunity against COVID-19 were at considerably lower risk of infection and hospitalisation as the number of family members with immunity from a previous infection or full vaccination increased, according to a nationwide study in Sweden, carried out by researchers at Umeå University.

While there is plenty of evidence to show vaccines strongly reduce the risk of COVID-19, less is known about the influence of vaccination on transmission of the virus in high-risk environments, such as within families.

The researchers found there was a dose-response association between the number of immune individuals in each family and the risk of infection and hospitalisation of non-immune family members in a study involving 1.8 million individuals from more than 800,000 families.

“The results strongly suggest that vaccination is important not only for individual protection, but also for reducing transmission, especially within families, which is a high-risk environment for transmission,” says Peter Nordström, professor of geriatric medicine at Umeå University.

“It seems as if vaccination helps not only to reduce the individual’s risk of becoming infected, but also to reduce transmission, which in turn minimises not only the risk that more people become critically ill, but also that new problematic variants emerge and start to take over,” said Marcel Ballin, co-author of the study. “Consequently, ensuring that many people are vaccinated has implications on a local, national, and global scale.”

Small financial incentives increase vaccination rates

A large-scale trial in Sweden succeeded in increasing the vaccination rate by four percentage points with the modest inducement of €20 (200 Swedish kronor). The promised reward helped to raise the already high rate in the trial from 72 percent to 76 percent.

“Our study shows that financial incentives can increase vaccination rates, even in places like many EU countries where they are already high,” said behavioural economist Armando Meier, senior research fellow at the University of Lausanne, Switzerland, who is co-author of the research published in Science.

The study was conducted between May and July 2021 with a representative sample of around 8,300 people between 18 and 49 years old. As soon as a vaccination was approved for their age group, the study participants were asked through an online survey whether or not they intended to get vaccinated.

Participants were then randomly assigned to five different groups. The members of the first group were promised a financial reward if they got vaccinated within 30 days. In three of the other groups, the scientists used other methods to try to increase the vaccination rate, such as sharing information on the safety and effectiveness of COVID-19 vaccines and emphasising that vaccination helps others.

Participants in the fifth group, which served as a control group, were not offered anything.

The researchers checked whether the individuals had actually been vaccinated against COVID-19 in the following 30 days through an anonymous linkage with data from the Swedish health authorities. They found that the prospect of a payment not only increases the declared vaccination intention, but actually leads to higher vaccination uptake.

“We also discovered, somewhat surprisingly, that the vaccination rate rose for everyone, regardless of gender, age and level of education. This indicates that monetary incentives have the potential to increase the rate among people regardless of background. The results also show that the incentives have an effect even in countries with relatively high vaccination levels such as Sweden”, said Erik Wengström, professor of economics at Lund University.

By contrast, other methods with which the researchers attempted to influence the behaviour of the participants were less successful. These included asking participants to name people close to them whom they could protect by getting vaccinated. While these “nudges” increased intentions to vaccinate in the short term, like information and reminders, they ultimately failed to translate into higher vaccination uptake.

Co-author Florian Schneider said, “The results put into perspective the fear that financial rewards are counterproductive and could deter undecided individuals from getting vaccinated, by fuelling suspicion, for instance. On the contrary, even modest monetary incentives can have a positive effect on the vaccination rate.”

The researchers also looked at whether it could it be cost effective for governments to pay people to get vaccinated.

“There is no detailed cost analysis in the study, but it is reasonable to assume that it would be cost-effective for society. The incentives can be considered as a stimulus package, transferring money from the government to people’s pockets, which at the same time would save people’s lives,” said co-author Pol Campos-Mercade.

“Even with low incentives, we can increase the vaccination rate against COVID-19. The result does not necessarily mean that we should pay people; we do not take a stand on whether it is ethically acceptable to pay people to get vaccinated or not. However, as the pandemic continues, incentives should be one of the tools worth considering in the fight to reduce the spread of COVID-19,” said Wengström.

Nordics place limits on use of Moderna’s COVID-19 vaccine

Denmark, Finland and Sweden have paused the use of Moderna’s COVID-19 vaccine in younger people, over concerns about the risk of myocarditis.

Although extremely rare, the condition, which causes inflammation of the heart muscle, has been linked to Moderna’s vaccine around the world.

Cases of myocarditis occur more often in adolescents and adults under 30 years of age, more often in males than in females, more often after a second dose of vaccine than after a first dose.

Sweden now advises the Moderna vaccine should not be given to people under 30, while Finland and Denmark advise against its use in those under 18 years of age.

Swiss diagnostics specialist to launch combined COVID-19 self-test and passport app

Achiko AG has launched a pilot programme in Indonesia of its non-invasive, saliva-based COVID-19 diagnostic test, AptameX, combined with its digital health passporting app, in one integrated platform and said it is in the process of getting EU CE mark approval, with a view to launching the diagnostic/passport combination in Europe.

It is expected that COVID-19 will be present for years to come and pose an ongoing threat to people’s health and well-being, and the economies for many countries, said Steven Goh, CEO of Achiko. “Against this backdrop, the cost of testing and the ease of managing test results become a key success factor in the fight against the ramifications of the pandemic. The combination of AptameX and [the passport app] can make testing affordable to workplaces and communities and bring the cost of frequent testing down,” he said.

The first stage of the pilot will be held in three sites in Indonesia, with the objective of confirming health economics and showcasing the service. Zurich-based Achiko is currently hiring and training staff to support commercial roll out.

Moderna to invest $500M to manufacture COVID-19 vaccines in Africa

US biotech Moderna announced it will build a mRNA vaccines facility in Africa with the goal of producing up to 500 million doses per annum. The company anticipates investing up to $500 million in this new facility, which is expected to include drug substance manufacturing with the opportunity for fill/finish and packaging capabilities at the site. It will begin the process of selecting a country and a site soon.

“We have been humbled to play a critical role in combatting the COVID-19 pandemic globally with our mRNA vaccine. We view Moderna’s work as only just beginning,” said Stephane Bancel, Moderna CEO. “We are determined to extend Moderna’s societal impact through the investment in a state-of-the-art mRNA manufacturing facility in Africa.”

“While we are still working to increase capacity in our current network to deliver vaccines for the ongoing pandemic in 2022, we believe it is important to invest in the future. We expect to manufacture our COVID-19 vaccine, as well as additional products within our mRNA vaccine portfolio at this facility,” Bancel said.

To date, Moderna has supplied more than 500 million doses of its COVID-19 vaccine, and recently announced several initiatives aimed at continuing to increase capacity “at a significant pace”.

EMA changes its stance on Pfizer/BioNTech vaccine boosters

The European Medicines Agency has changed its recommendations on booster doses of the Pfizer/BioNTech COVID-19 vaccine, saying boosters “may be considered” at least six months after the second dose for people aged 18 years and older.

This is an about turn for EMA, which on 2 September put out a joint statement with the European Centre for Disease Control, saying evidence on vaccine effectiveness and duration of protection showed that all vaccines authorised in the EU remained effective in preventing COVID-19-related hospital admissions, severe disease and death.

The change is based on the evaluation of data showing a rise in antibody levels when a booster dose of the Pfizer vaccine is given approximately six months after the second dose in people from 18 to 55 years old.

A number of countries in Europe have gone ahead with booster programmes despite EMA’s emergency use authorisation for Pfizer’s vaccine not specifying it is safe and effective when used in this way.

EMA said the risk of inflammatory heart conditions or other very rare side effects after a booster is not known and is being carefully monitored. More information about the booster recommendations for Pfizer’s vaccine will be available in the updated product information.

EMA is also currently evaluating data to support a booster dose for Moderna’s COVID-19 vaccine.

At the same time, EMA said an extra dose of either Pfizer or Moderna’s vaccines may be given to people with severely weakened immune systems, at least 28 days after their second dose.

The recommendation comes after studies showed that an extra dose of these vaccines increased the ability to produce antibodies against the SARS-CoV-2 virus in organ transplant patients with weakened immune systems.

As yet, there is no direct evidence that the ability to produce antibodies in these patients protects against COVID-19, but it is expected that the extra dose would increase protection at least in some patients. The product information of both vaccines will be updated to include this recommendation.

Pfizer/BioNTech vaccine good at cutting hospital admissions, but effectiveness at preventing infections shows steady decline

Real world US data shows two doses of the Pfizer/BioNTech vaccine are 90% effective at preventing COVID-19 hospital admission across all variants of the SARS-CoV-2 virus, including Delta, for at least six months, according to a study published in The Lancet.

However, over time, two doses are not so good at preventing infections, with effectiveness declining steadily, from 88% within one month of receiving two vaccine doses, to 47% after six months.

The researchers say this study underscores the importance of improving COVID-19 vaccination rates worldwide and monitoring vaccine effectiveness to determine which populations should be prioritised to receive boosters.

“Our study confirms that vaccines are a critical tool for controlling the pandemic and remain highly effective in preventing severe disease and hospitalisation, including from Delta and other variants of concern. Protection against infection does decline in the months following a second dose,” said Sara Tartof, of the Kaiser Permanente Southern California Department of Research & Evaluation, one of the study authors.

The researchers analysed 3.4 million electronic health records from the Kaiser Permanente Southern California health system between 4 December 2020, and 8 August 2021. During this time, 5.4% (184,041 people) were infected with SARS-CoV-2. Among those who were infected, 6.6% (12,130) were hospitalised. The average time since being fully vaccinated was between three to four months.

Whole genome sequencing showed the Delta variant comprised 28% of the overall proportion of positive sequences. During the study period, the proportion of positive cases in the US attributed to Delta increased from 0.6% in April 2021 to nearly 87% by July 2021, confirming the Delta variant had become the dominant strain.

Vaccine effectiveness against Delta infections at one month after two doses of vaccine was 93% and fell to 53% after four months. Effectiveness against other variants one month after receiving two doses was 97% and declined to 67% after four months.

The researchers did not observe a difference in the rate of waning between SAR-CoV-2 variant type, suggesting reduced protection from infection was similar regardless of the variant identified and therefore that declining effectiveness is a result of waning vaccine effect affecting all strains in circulation, rather than a variant that is insensitive to the vaccine.

EMA concludes there is link between J&J vaccine and rare blood clots

The safety committee of the European Medicines Agency has concluded that there is a possible link between rare cases of venous thromboembolism (VTE) and Johnson & Johnson’s single dose COVID-19 vaccine.

VTE occurs when a blood clot forms in a deep vein, usually in a leg, arm or groin, and travels to the lungs, blocking the blood supply, with possible life-threatening consequences.

This safety issue is distinct from another very rare side effect, of thrombosis with thrombocytopenia syndrome, when blood clots occur despite a low level of the platelets that cause blood to clot.

VTE was included in EMA’s risk management plan for Johnson & Johnson’s COVID-19 vaccine, because a higher proportion of cases of VTE observed within the vaccinated group versus the placebo group in the large clinical study which was used to authorise the vaccine.

EMA has now reviewed new data from this study, as well as new evidence from another large clinical trial. In the second study there was no increase in venous thromboembolic events among individuals who received the Johnson & Johnson vaccine. However, EMA also reviewed real world data from vaccination campaigns, and when taking all evidence into account, the safety committee concluded there is a “reasonable possibility” rare cases of VTE are linked to this vaccine .

EMA is recommending listing VTE as a rare side effect of the Johnson & Johnson vaccine in the product information, together with a warning to raise awareness among healthcare professionals and people receiving the vaccine, especially those who may have an increased risk of VTE.

The safety committee also assessed cases of immune thrombocytopenia (ITP) - in which the immune system mistakenly targets blood platelets that are needed for normal blood clotting - that have been reported following vaccination with Johnson & Johnson’s and AstraZeneca’s Covid-19 vaccines.

As a result, EMA recommended updating the product information of both vaccines to include ITP as an adverse reaction with an unknown frequency.

Over a third of COVID-19 Patients diagnosed with at least one long-COVID symptom

A total of 37% of people had at least one long-COVID symptom diagnosed in the 3-6 month period after COVID-19 infection, with the commonest symptoms being breathing problems, abdominal symptoms, fatigue, pain and anxiety/depression.

Researchers at Oxford University investigated long COVID symptoms in over 270,000 people recovering from COVID-19 infection, using patient records from the US TriNetX network, which holds records of 81 million people.

In all, 57% of patients with a recorded diagnosis of COVID-19 subsequently presented to their doctors with symptom(s) of long COVID between 0 – 6 months after infection. More than a third (37%) did not report until three to six months after they contracted COVID-19, indicating they are not persisting acute symptoms. The researchers say it may be that new symptoms emerge some time after initial infection.

Severity of infection, age, and sex, affected the likelihood of long-COVID symptoms, with long-COVID symptoms more frequent in those who had been hospitalised. They were also slightly commoner in women. There was no difference seen between people of different ethnicities.

Older people and men had more breathing difficulties and cognitive problems, whereas young people and women had more headaches, abdominal symptoms and anxiety/depression. Many patients had more than one long-COVID symptom, and symptoms tended to co-occur more as time progressed.

The study, published in PLOS Medicine, does not explain what causes long-COVID symptoms, or say how severe they are, or how long they will last.

Max Taquet, of Oxford University, who led the analysis said, “The results confirm that a significant proportion of people, of all ages, can be affected by a range of symptoms and difficulties in the six months after COVID-19 infection. These data complement findings from self-report surveys, and show that clinicians are diagnosing patients with these symptoms. We need appropriately configured services to deal with the current and future clinical need.”

Research of different kinds is urgently needed to understand why not everyone recovers rapidly and fully from COVID-19, said Paul Harrison, who headed the study. “We need to identify the mechanisms underlying the diverse symptoms that can affect survivors. This information will be essential if the long-term health consequences of COVID-19 are to be prevented or treated effectively,” he said.

EMA looking at use of Moderna COVID-19 vaccine as booster

The European Medicines Agency has started evaluating an application for the use of a booster dose of Spikevax, Moderna’s COVID-19 vaccine, to be given at least 6 months after the second dose in people aged 12 years and older.

Booster doses would be given to vaccinated people who have completed their primary vaccination, to restore protection after it has waned.

EMA said it will carry out an accelerated assessment of data submitted, including results from an ongoing clinical trial. Based on this review, it will recommend whether the product information should be updated to say booster doses are appropriate.

While it is looking at the file, EMA and the European Centre for Disease Prevention and Control (ECDC) have both said they do not consider the need for COVID-19 vaccine booster doses to be urgent in the general population, EMA’s stance is that it is evaluating Moderna’s application to ensure evidence is available to support further doses as necessary.

Advice on how vaccinations should be given remains the prerogative of immunisation experts in each EU member state. EMA said member states “may already consider preparatory plans” for giving boosters and additional doses.

Spikevax is currently authorised for use in people aged 12 and older.

COVID-19 pandemic caused biggest decrease in life expectancy since World War 2

The COVID-19 pandemic has triggered life expectancy losses not seen since World War 2 in western Europe, and which exceed those in central and eastern Europe following the break up of the Soviet Union, according to new research.

The researchers brought together a dataset on mortality from 29 countries, spanning most of Europe, the US and Chile, for which official death registrations for 2020 have been published. In 27 of the 29 countries there were reductions in life expectancy in 2020, and at a scale which wiped out years of progress on mortality, according to a paper published in the International Journal of Epidemiology.

Women in 15 countries and men in 10 countries were found to have a lower expectancy at birth in 2020 than in 2015, a year in which life expectancy was already negatively affected by a significant flu season.

The study was led by scientists at Oxford University’s Centre for Demographic Science. Author José Manuel Aburto said, “For western European countries such as Spain, England and Wales, Italy, Belgium, among others, the last time such large magnitudes of declines in life expectancy at birth were observed in a single year was during World War 2.”

The scale of the life expectancy losses was sobering across most countries studied, with twenty two countries having losses in life expectancy greater than six months in 2020. “Females in eight countries and males in 11 countries experienced losses larger than a year,” Aburto said. “To contextualise, it took on average 5.6 years for these countries to achieve a one year increase in life expectancy recently. [That] progress [was] wiped out over the course of 2020 by COVID-19.”

Across most of the 29 countries, males saw larger life expectancy declines than females. The largest drop was observed among males in the US, who saw a decline of 2.2 years relative to 2019 levels, followed by males in Lithuania, where 1.7 years was wiped off life expectancy.

Another author, Ridhi Kashyap said the large declines in life expectancy observed in the US can partly be explained by the notable increase in mortality at working ages observed in 2020. “In the US, increases in mortality in the under 60 age group contributed most significantly to life expectancy declines, whereas across most of Europe increases in mortality above age 60 contributed more significantly,” Kashyap said.

In addition to these age patterns, the analysis reveals that most life expectancy reductions across different countries were attributable to official COVID-19 deaths.

“While we know that there are several issues linked to the counting of COVID-19 deaths, such as inadequate testing or misclassification, the fact that our results highlight such a large impact that is directly attributable to COVID-19 shows how devastating a shock it has been for many countries,” said Kashyap. “We urgently call for the publication and availability of more disaggregated data from a wider range of countries, including low- and middle-income countries, to better understand the impacts of the pandemic globally.”

Life expectancy refers to the average age to which a newborn will live if current death rates continued for their whole life. It does not predict an actual lifespan, but rather provides a snapshot of current mortality conditions. This allows for a comparison of the size of the mortality impacts of the pandemic between different countries and populations.

Anglo German research project finds possible factor contributing to severe COVID-19

Researchers at the Institute of Medical Virology at Goethe-University, Frankfurt am Main, and at the School of Biosciences at Kent University in the UK have identified a protein they say may critically contribute to severe forms of COVID-19.

They found that the infection of human cells with SARS-CoV-2 virus resulted in increased levels of CD47, a protein found on the cell surface. CD47 acts as a ‘do not eat me’ signal to the immune system, protecting cells from being destroyed. Virus-induced CD47 on the surface of infected cells is thought to protect them from immune system recognition, enabling the production of larger amounts of virus, resulting in more severe disease.

Well-known risk factors for severe COVID-19 such as older age and diabetes are associated with higher CD47 levels. High CD47 levels also contribute to high blood pressure, which is a large risk factor for COVID-19 complications such as heart attack, stroke, and kidney disease.

The researchers say their data suggest that age and virus-induced high CD47 levels contribute to severe COVID-19 by preventing an effective immune response and increasing disease-associated tissue and organ damage. Drugs targeting CD47 are in development so this discovery may result in improved COVID-19 therapies.

Martin Michaelis, professor of molecular medicine at Kent University, said, “We may have identified a major factor associated with severe COVID-19. This is a huge step in combatting the disease and we can now look forward to further progress in the design of therapeutics.”

Jindrich Cinatl of the Institute of Medical Virology, Goethe-University, said the additional insights into the disease processes underlying COVID-19 may help in the design of better therapies. “Through this avenue, we have achieved a major breakthrough and exemplified that the fight against the disease continues.”

International consortium publishes map of antibodies binding to SARS-CoV-2 virus

An international group of scientists led by the La Jolla Institute for Immunology in the US have published a detailed map of where therapeutic antibodies bind to SARS-CoV-2, which they say will guide the development of more effective COVID-19 antibody therapies and help develop effective vaccines against viral variants.

The researchers say the findings, published in Science, propel COVID-19 research in three key ways. Hundreds of antibodies contributed by over 50 different organisations around the world were classified and mapped to shows exactly where each one binds on the spike protein of SARS-CoV-2.

The research describes the neutralising strength, or potency, of each antibody and the likelihood it could offer protection against viral variants.

Antibodies with similar footprints on the spike are grouped into communities and the researchers show how antibodies from these different communities could be combined in antibody cocktails to target the virus.

"This map provides a reference to help predict which antibodies are still effective against SARS-CoV-2 variants of concern like the currently surging Delta variant," says Erica Ollmann Saphire, who leads the global Coronavirus Immunotherapeutic Consortium (CoVIC).

The researchers found three different groups of antibodies that are resistant to mutations in the SARS-CoV-2 spike protein and which could target vulnerable sites on the spike protein, even as it mutates. “We now have a framework for selecting durable antibody cocktails for COVID-19 treatment,” said Saphire.

CoVIC includes about 370 therapeutic antibodies from 59 different groups across academic labs and small biotechs, to large pharmaceutical companies.

The research provides a framework to understand, on a global scale, which antibodies are effective (or not) against which variants. This information will be key in ranking the pool of antibodies and deciding which to advance to further study.

All the data are freely accessible to other researchers looking to compare and contrast antibodies against the SARS-CoV-2 spike. The combined information will help determine which antibodies would be candidates to move into clinical development.

Indian vaccines company invests £50M in UK COVID-19 vaccines manufacturer

Oxford Biomedica announced that Serum Life Sciences Ltd, a subsidiary company of Serum Institute of India, the world’s largest vaccines manufacturer, has agreed to invest just over £50 million to fund development of its COVID-19 vaccine manufacturing facility based Oxford.

The facility, called Oxbox, currently has three 1,000 litre bioreactors producing COVID-19 vaccine. The new investment will enable the rest of the facility to be developed, to increase production of vaccines and of viral vectors for use in gene therapy.

“Serum Institute of India has played a big part in the fight against COVID-19, as have we, and we look forward to a strong and collaborative relationship,” said John Dawson, CEO of Oxford Biomedica. “This investment will allow us to expand capacity at Oxbox at a time when our business development pipeline has never looked stronger.”

Oxford Biomedica’s commercial fortunes have been transformed by its agreement with AstraZeneca to manufacture the pharma’s COVID-19 vaccine. In May, it was announced that AstraZeneca was increasing the number of batches required from Oxford Biomedica in the second half of the 2021.

As a result, Oxford Biomedica increased its forecast for cumulative revenues from the contract to in excess of £100 million by the end of 2021.

In the first half of 2021, Oxford Biomedica’s revenue increased by 139% to £81.3 million, up from £34.0 million in the same period in 2020.

AstraZeneca has committed to supply its COVID-19 at cost during the current pandemic.

Pfizer and BioNTech to provide 500M additional COVID-19 vaccine doses at cost for poor countries

Pfizer and BioNTech announced plans to expand their agreement with the US government and to supply an additional 500 million doses of their COVID-19 vaccine at a not-for-profit price for donation to poor countries.

The expanded agreement brings the total number of doses to be supplied to the US government for donation to these countries to one billion.

The US will allocate doses of the Pfizer/BioNTech COVID-19 vaccine to 92 low- and lower-middle-income countries, and to the 55 member states of the African Union. Deliveries of the initial 500 million doses began in August 2021, and the total one billion doses under the expanded agreement are expected to be delivered by the end of September 2022.

The current plan is to produce these doses in Pfizer’s US facilities.

“In just nine months, Pfizer and BioNTech have delivered our COVID-19 vaccine to 130 countries and territories in every region of the world, and our expanded collaboration with the US will help us bring even more doses to those in need,” said Albert Bourla, CEO of Pfizer.

Ugur Sahin, CEO and co-founder of BioNTech said, “In the short term, we have pledged to deliver at least one billion doses this year and at least one billion doses next year to low- and middle-income countries. In parallel, we are exploring how to build a sustainable mRNA production infrastructure in low-income countries to democratise access to vaccines in the mid- and long-term. This applies to both individual production steps and complete manufacturing.”

To date, Pfizer and BioNTech have shipped more than 1.5 billion COVID-19 vaccine doses worldwide.

J&J says real world evidence and phase III data confirm strong and lasting protection of its single-shot COVID-19 vaccine.

Johnson & Johnson announced new data showing that protection against COVID-19 increases when a booster shot of its vaccine is administered, with the safety profile remaining consistent and the vaccine generally well-tolerated when administered as a booster.

“Our large real world evidence and phase III studies confirm that the single shot Johnson & Johnson vaccine provides strong and long lasting protection against COVID-19-related hospitalisations. Additionally, our phase III trial data further confirm protection against COVID-19-related death,” said Mathai Mammen, global head of research & development, Johnson & Johnson.

“It is critical to prioritise protecting as many people as possible against hospitalisation and death given the continued spread of COVID-19,” said Paul Stoffels, chief scientific officer. “A single shot COVID-19 vaccine that is easy to use, distribute and administer, and that provides strong and long lasting protection is crucial to vaccinating the global population. At the same time, we now have generated evidence that a booster shot further increases protection against COVID-19 and is expected to extend the duration of protection significantly.”

In what it says is the largest real world evidence study for a COVID-19 vaccine reported to date in the US, the vaccine was 81% effective in preventing COVID-19-related hospital admissions. There was no evidence of reduced effectiveness over the study duration, including when the Delta variant became dominant in the US.

The study included 390,000 people who received the Johnson & Johnson COVID-19 vaccine and approximately 1.52 million matched unvaccinated people.

When a booster of the Johnson & Johnson COVID-19 vaccine was given two months after the first dose, antibody levels rose to four to six times higher than seen after the single shot.

When a booster of the Johnson & Johnson COVID-19 vaccine was given six months after the single shot, antibody levels increased nine-fold one week after the booster, and continued to climb to 12-fold higher four weeks after the booster. All rises were irrespective of age.

New algorithm predicts risk of serious COVID-19 post vaccination

Researchers in the UK have used population level databases to develop an algorithm that can predict individuals who are at risk of hospitalisation and death if they contract COVID-19, despite being fully vaccinated.

The QCovid tool is based on data from 6.9 million vaccinated individuals, of whom 5.2 million had received two doses, a cohort that is representative of the UK population as a whole. Health databases are linked, meaning each person could be followed up via their general practitioner records, by referring to COVID-19 testing results and through hospital admission and death records.

Vaccines are providing a high level of protection but a small number of people are still experiencing serious illness if they get COVID-19, with age remaining by far the greatest risk factor. Also remaining at risk are those whose immune systems are compromised as a result of chemotherapy, because they are taking immune-supressing medicines following a solid organ transplant, or who have HIV/AIDS.

Applying the algorithm to UK data on hospital admissions and deaths showed some groups that were classified as being at high risk before vaccination, are no longer at higher risk of hospitalisation and death once they have been vaccinated. That includes ethnic minorities, apart from those of Indian or Pakistani heritage.

The risks identified by the algorithm have been validated against separate datasets, showing what the researchers say is “excellent ability” to identify those at highest risk of death and “very good” ability to identify who will need hospital care. The research was published in the British Medical Journal.

The tool can be used to identify those who would benefit from booster doses of vaccine or to decide who should receive new treatments, such as expensive antibody drugs, that help the body to fight infections.

Pfizer and BioNTech announce positive results for COVID-19 vaccine in children age 5 - 11

Reporting the first results of a pivotal trial of any COVID-19 vaccine in children under 12 years of age, Pfizer and German biotech BioNTech said their mRNA vaccine was safe, well tolerated and showed robust neutralising antibody responses in children age 5 – 11.

The companies said they will submit the data to the European Medicines Agency, the US Food and Drug Administration and other drug regulators as soon as possible.

The trial used two doses of 10 micrograms administered 21 days apart. While that is a smaller dose than the 30 microgram dose used for people 12 and older, the antibody responses were comparable.

“We are eager to extend the protection afforded by the vaccine to this younger population, subject to regulatory authorisation, especially as we track the spread of the Delta variant and the substantial threat it poses to children,” said Albert Bourla, CEO of Pfizer.

Since July, cases of COVID-19 in children have risen by about 240% in the US, Bourla noted. “These trial results provide a strong foundation for seeking authorisation of our vaccine for children 5 to 11 years old.”

The data was for 2,268 participants who were 5 to 11 years of age. Top line readouts for the other two age cohorts from the trial, of children 2 - 5 years of age and children 6 months to 2 years of age, are expected before the end of the year.

A request to the EMA to update the EU conditional marketing authorisation is now planned.

Trial of COVID-19 vaccine booster and immunogenicity enhancer starts in Manchester

US biotech Gritstone Bio announced the first volunteer has been dosed in a phase I trial evaluating the ability of its second generation mRNA COVID-19 vaccine, GRT-R910, to boost and expand the immunogenicity of first generation COVID-19 vaccines in people aged 60 years or older. The single centre study is being conducted by Manchester University and its associated teaching hospital.

GRT-R910 uses lipid nanoparticles to deliver a broad set of antigens against SARS-CoV-2, including both stabilised spike protein and highly conserved regions of the virus viral protein. Gritstone says the self-amplifying properties and extended duration and magnitude of antigen production may make it possible to lower vaccine doses, or eliminate the need for repeat administration, and has potential to elicit immune responses across SARS-CoV-2 variants.

“Since viral surface proteins like the spike protein are evolving and sometimes partially evading vaccine-induced immunity, we designed GRT-R910 to have broad therapeutic potential against a wide array of SARS-CoV-2 variants, by also delivering highly conserved viral proteins,” said Andrew Allen, CEO of Gritstone.

The Gritstone trial, which is initially expected to enrol 20 volunteers, will explore the ability of GRT-R910 to boost and expand the immunogenicity of AstraZeneca's first-generation COVID-19 vaccine in healthy adults over 60 years of age.

“The observed waning of vaccine-elicited immune responses, particularly in older individuals, coupled with the prevalence of emerging variants, highlights the need for continued vigilance to keep COVID-19 at bay,” said Andrew Ustianowski, consultant in infectious diseases and tropical medicine at North Manchester General Hospital, who is lead investigator. “Using GRT-R910 as a boost vaccination is expected to elicit strong, durable, and broad immune responses, which are likely critical to maintaining protection in this vulnerable elderly population with increased mortality risk.” Ustianowski said.

EU to prioritise speeding up global COVID-19 vaccination

With more than 70 per cent of adults in the EU fully vaccinated against COVID-19, the next and most urgent priority is to speed up global vaccination, Commission president Ursula von der Leyen said in the annual state of the union address.

“With less than 1% of global doses administered in low-income countries, the scale of injustice and the level of urgency are obvious. This is one of the great geopolitical issues of our time,” said von der Leyen.

The EU is investing €1 billion to ramp up mRNA production capacity in Africa and has so far committed to share 250 million doses. The Commission will add a new donation of another 200 million doses by the middle of next year.

At the same time, the EU will continue its efforts in Europe, aiming to address the “worrisome divergences” in vaccination rates between member states. “Let's do everything possible to ensure that this does not turn into a pandemic of the unvaccinated,” said von der Leyen.

The EU has an additional 1.8 billion doses of COVID-19 vaccines on hand and ready to use when booster shots are needed.

The final priority is to strengthen preparedness for future pandemics by setting up the European Health Union. This will be backed by a new health preparedness and resilience research mission covering the whole of the EU, and backed by investment of €50 billion by 2027.

Dashboard brings together all research on the impact of COVID-19 on cancer care

Cancer research and care groups in the UK have set up the Covid-19 research dashboard, a public resource that lists research projects looking at the impact of Covid-19 on cancer care and patients.

The dashboard was developed by the National Cancer Research Institute, Cancer Research UK, the National Cancer Registration and Analysis Service and the Cancer Alliance Data, Evaluation and Analysis Service. The intention is to drive collaborations in the field and identify gaps in research activity or opportunities for new research.

The Covid-19 pandemic has impacted cancer services and patients, prompting new research to quantify and understand this impact across the care pathway, including changes to the detection, treatment, and long-term follow-up of cancers and the effects of the pandemic, direct and indirect, on patients’ experiences and quality of life.

The list of ongoing and completed research projects has been collated and made publicly available to enable researchers to identify gaps in activity and opportunities for new research; avoid duplication of effort, support collaborations in the field and to understand potential data needs of this new research area.

To date, 89 studies have been identified and uploaded to the dashboard and it is hoped that researchers will submit their studies via an online form to ensure the dashboard remains a useful and up-to-date resource.

Nobellists and former heads of state call on Germany to waive IP rules on COVID-19 vaccines

More than 140 Nobel laureates and former world leaders have written an open letter to the three candidates for the position of next German chancellor, Annalena Baerbock, Armin Laschet, and Olaf Scholz, calling on them to support a waiver of IP rights on COVID-19 vaccines.

The letter says Germany has a significant role to play in global efforts to bring the COVID-19 pandemic to an end, and the impact would be of huge significance to people in Germany and around the world.

German publicly-funded science led to the development the Pfizer/BioNTech vaccine, but this and other vaccines are “zero per cent effective” for those who cannot access them, the letter says.

“In light of this we are deeply concerned with Germany’s continued opposition to a temporary waiver of the World Trade Organization’s intellectual property rules, which thwart more rapid production of COVID-19 vaccines and access to technologies,” says the letter.

There are qualified manufacturers around the world which, with a temporary waiver of intellectual property rights and the necessary knowledge and technology transfer, could produce billions of additional doses of vaccines.

The position taken by Germany and some other countries is undermining the will of the more than 100 countries that do support negotiations on a waiver. “We write to express our hope that, after its general election, Germany will change its position” and will support negotiations on the waiver, the signatories say.

Dutch biotech Pharming announces results of trials treating COVID-19 with its anti-inflammatory drug

Pharming has announced top line results from two randomised, open label clinical trials of its immune-modulating drug Ruconest in the treatment of patients hospitalised with COVID-19.

The aim was to show the product prevented severe SARS-CoV-2 infection. In one study held in the US, patients treated with Ruconest plus standard of care had statistically significant lower disease severity scores at day seven, compared to patients who received standard of care alone.

However, in the second, investigator-led study, conducted in Switzerland, Brazil and Mexico, and funded through the Swiss National Research programme in COVID-19 of the National Science Foundation, there was no difference in disease severity at day seven between Ruconest treated patients and those receiving standard of care alone.

Leiden-based Pharming said the results of the Swiss study are difficult to interpret because there was a significant difference in disease severity at baseline, with patients in the Ruconest arm having more severe disease.

Anurag Relan, Pharming’s Chief Medical Officer said the results support the initial hypothesis on the need to control hyper-inflammatory processes in patients with severe COVID-19 infection. “It is unfortunate we cannot draw many conclusions from the investigator-led study, due to the imbalance between the Ruconest-arm and the control group at the start of the trial. We will analyse the full results of these studies as we design future clinical trials with Ruconest for the treatment of COVID-19,” Relan said.

UK government cancels order for 100M doses of COVID-19 vaccine from French biotech Valneva

French biotech Valneva said it is continuing phase III development of its COVID-19 vaccine after the UK government cancelled its order for 100 million doses.

The UK government alleges Valneva is in breach of its obligations under the contract between the two, something the company “strenuously denies”.

No details of the exact nature of the dispute were disclosed. The cancellation was unexpected, given the UK government’s investment in Valneva’s manufacturing facility in Livingston, Scotland, where commercial supplies of the vaccine are already being made. The government investment was due to be recouped once vaccine started to be supplied under the contract.

Valneva also has received UK government support with the clinical development of the vaccine, which is the only one in Europe using a whole, inactivated SARS-CoV-2 virus. This was seen as a key technology and an important way of spreading the risk in vaccines in development at the point Valneva was awarded the contract, worth up to €1.4 billion, a year ago.

The phase III clinical testing of the vaccine is ongoing under the supervision of Public Health England, with results expected to be available early in the fourth quarter of 2021. Last month, Valneva said it had started submission of data for the conditional approval of the vaccine with the UK Medicines and Healthcare products Regulatory Agency, and was expecting initial approval could be granted in late 2021.

Valneva said it has, “has worked tirelessly, and to its best efforts” on the collaboration with the UK government and will continue to develop the vacccine.

EMA adds to list of rare side effects of AstraZeneca COVID-19 vaccine

The European Medicines Agency has listed the rare autoimmune disorder, Guillain-Barre syndrome as a possible side effect of the AstraZeneca COVID-19 vaccine, following the latest review of reports of adverse events following administration of the product.

The information leaflet will be updated to reflect this. Pains in the legs and arms or stomach and influenza-like symptoms have also been included in the product information as side effects.

This follows the addition of a warning to raise awareness of cases of Guillain-Barré syndrome in July, since when EMA has been keeping reports of the syndrome under close monitoring. In a meeting earlier this week it assessed additional data supplied by AstraZeneca and the results from a scientific literature review.

A total of 833 cases of Guillain-Barré syndrome were reported with the vaccine worldwide up to 31 July 2021, at which point more than 592 million doses had been administered.

Based on the assessment of the data, and taking into account advice from neurological experts, EMA has now concluded that a causal relationship between the AstraZeneca vaccine and Guillain-Barré syndrome is at least a reasonable possibility and that the syndrome should therefore be added to the product information as a side effect.

Leaders of the Covax initiative hit out at inequity in vaccine supplies

The global picture of access to COVID-19 vaccines is “unacceptable” according to the organisations leading the Covax initiative, which was set up to ensure equitable distribution, in their latest supply forecast.

To date, only 20% of people in low- and lower-middle-income countries have received a first dose of vaccine compared to 80% in high- and upper-middle income countries, according to a joint statement by the Coalition for Epidemic Preparedness Innovations, Gavi, the Vaccine Alliance and the World Health Organisation.

Covax’s ability to protect the most vulnerable continues to be hampered by export bans, the prioritisation of bilateral deals by manufacturers and countries, ongoing challenges in scaling up production by some key producers, and delays in filing for regulatory approval, the statement says.

According to the supply forecast, Covax expects to have access to 1.425 billion doses of vaccine in 2021. Of these doses, approximately 1.2 billion will be available for lower income economies, enough to protect 20% of the population, or 40% of all adults, in 92 countries. The key Covax milestone of two billion doses released for delivery is now expected to be reached in the first quarter of 2022.

Covax says it is working closely with governments to ensure the conditions are in place to ensure successful rollout of vaccines. It is now calling on donors and manufacturers to recommit their support and prevent further delays to equitable access.

Manufacturers are asked to deliver vaccine supplies in accordance with firm commitments and provide transparency on timelines, to allow countries to plan in advance.

Countries which are ahead of Covax in manufacturer queues and that have already achieved high vaccination coverage, are asked to give up their places in the queue to Covax.

EMA assessing use of Pfizer/BioNTech Covid-19 vaccine in boosters

EMA has started evaluating an application for the use of a booster dose of the Pfizer/BioNTech COVID-19 vaccine, to be given six months after the second dose in people aged 16 years and older.

The booster doses would be given to vaccinated people to restore protection after it has waned.

EMA said it will carry out an accelerated assessment of data, including results from an ongoing clinical trial in which around 300 adults with healthy immune systems received a booster dose approximately six months after the second dose.

The outcome of this evaluation is expected within the next few weeks.

Separately, EMA is also assessing data from the literature on the use of an additional, third dose of an mRNA vaccine in severely immunocompromised people who do not achieve an adequate level of protection from standard primary vaccination and may need another dose as part of their primary vaccination.

Although EMA and the European Centres for Disease Control say they don’t consider the need for COVID-19 vaccine booster doses to be urgent, EMA is evaluating the application for boosters to ensure evidence is available to support further doses as necessary.

Advice on how vaccinations should be given remains the prerogative of the national immunisation advisory groups.

Row between Commission and AstraZeneca on COVID-19 vaccine supplies is over

AstraZeneca and the European Commission reached an agreement to end legal proceedings over the advance purchase agreement for the delivery of the COVID-19 vaccine.

Under the agreement, AstraZeneca has said it will deliver 60 million doses of the vaccine by the end of the third quarter 2021, 75 million by the end of the fourth quarter 2021 and 65 million by the end of the first quarter 2022. Member states will be provided with regular deliveries and there will be rebates in the event of any delays.

“We are fully committed to manufacture [the vaccine] for Europe following the release for supply of more than 140 million doses to date at no profit,” said Ruud Dobber, executive vice president of Biopharmaceuticals at AstraZeneca.

Legal proceedings by the European Commission against AstraZeneca were initiated in Brussels on 21 April 2021, and court hearings were scheduled for the end of September 2021.

To date, AstraZeneca and its partners have supplied more than 1.1 billion doses of vaccine to over 170 countries; approximately two thirds have gone to poorer countries.

Moderna to submit application for COVID-19 booster to European Medicines Agency

Moderna announced it has started submission to the U. Food and Drug Administration (FDA) for the evaluation of a booster dose of its COVID-19 vaccine and expects to submit data to the European Medicines Agency and other regulatory authorities around the world in the coming days.

The submitted data shows “robust antibody responses against the Delta variant,” said Stéphane Bancel, CEO of Moderna.

The phase II study of the vaccine was amended to offer a booster dose to interested participants six months following their second dose, with 344 volunteers taking up the offer. Neutralising antibody levels had waned significantly prior to boosting. The booster dose raised neutralising levels significantly.

After a third dose, a similar level of neutralising antibodies was seen across age groups, notably in older adults aged 65 and above. The safety profile following dose three was similar to that observed for the second dose.

New UK study finds that despite Delta variant vaccines remain effective in reducing serious illness

People who catch SARS-CoV-2 despite having received one or two doses of vaccine have significantly lower odds of severe disease or hospital admission than unvaccinated people, according to a large-scale study investigating COVID-19 breakthrough infections.

Researchers also found that the odds of experiencing Long COVID, with symptoms lasting 28 days or more after a positive test were cut in half for people who received two vaccines doses, in the study published in The Lancet Infectious Diseases journal.

Those most vulnerable to a breakthrough infection after their first vaccine dose included frail older adults aged 60 years and above, and older adults living with underlying conditions such as obesity, heart disease, kidney disease, and lung disease.

In all age groups, people living in deprived areas, such as densely populated urban settings, were more likely to experience a breakthrough infection.

“We are at a critical point in the pandemic as we see cases rising worldwide due to the Delta variant,” said co-author Claire Steves of King’s College London. The Delta variant is now causing most infections in Europe and the rest of the world, and other data shows vaccines are less effective against it.

“Breakthrough infections are expected and don’t diminish the fact that these vaccines are doing exactly what they were designed to do - save lives and prevent serious illness,” Steves said.

The researchers used self-reported data collected by the UK COVID symptom social media app. Of 1.2 million adults who reported to the app who received at least one dose of any vaccine between 8 December 2020 to 4 July 2021, fewer than 0.5% reported a breakthrough infection more than 14 days after their first dose. Of those who had received who received two doses, fewer than 0.2% experienced a breakthrough infection more than seven days after the second dose. In total, there were 2,370 positive cases after 971,504 second vaccine.

Among those who did experience a breakthrough infection, the odds of that infection being asymptomatic increased by 63% after one vaccine dose and by 94% after the second dose. Researchers also found that the odds of hospitalisation were reduced by approximately 70% after one or two doses, and that the odds of experiencing severe disease, defined as having five or more symptoms in the first week of illness, were lessened by approximately one third. In addition, the odds of Long COVID, having symptoms for 28 days or more after infection, were reduced by 50% after two doses.

No need for vaccine boosters say EMA and ECDC

Based on current evidence, there is no urgent need for the administration of booster doses of vaccines to fully vaccinated individuals in the general population, according to a technical report issued by the European Centre for Disease Prevention and Control (ECDC).

However, additional doses should be considered for people with severely weakened immune systems as part of their primary vaccination.

Evidence on vaccine effectiveness and duration of protection shows that all vaccines authorised in the EU are currently highly protective against COVID-19-related hospitalisation, severe disease and death.

At the same time, about one in three adults over 18 years is still currently not fully vaccinated. “In this situation, the priority now should be to vaccinate all those eligible individuals who have not yet completed their recommended vaccination course,” the European Medicines Agency said in a statement.

EMA is currently assessing data on booster doses, and said while it does this member states “may consider preparatory plans for administering boosters.”

‘Second wave’ COVID-19 vaccine starts phase III development with $213M Gates Foundation and CEPI funding

The first of the so-called second wave of COVID-19 vaccines, which have been designed from the ground up to be more accessible and affordable, has started a phase III clinical trial.

The vaccine, GBP510, developed by South Korean biotech SK Bioscience, will be administered in combination with an adjuvant from GlaxoSmithKline (GSK), which is intended to increase the immune response.

The randomised global trial will enrol around 4,000 participants from a range of countries to evaluate GBP510's safety and immunogenicity compared to the AstraZeneca/Oxford University COVID-19 vaccine. The study will be one of the first global phase III trials to directly compare two different COVID-19 vaccines.

"We are grateful that we were able to advance to the phase III study with the unprecedented support of global initiatives, including GSK, the Coalition for Epidemic Preparedness Initiative (CEPI), and the Bill & Melinda Gates Foundation,” said Jaeyong Ahn, CEO of SK Bioscience.

“While many countries have made good progress with vaccination, there remains a need for accessible and affordable COVID-19 vaccines to ensure equitable access and to protect people across the world,” said Thomas Breuer, chief global health officer at GSK.

The move to phase III follows positive interim phase I/II data which showed that all participants who received the adjuvanted vaccine developed strong neutralising antibody responses, demonstrating a 100% seroconversion rate. Neutralising antibody levels were between five and a maximum of eight times higher than in people who had recovered from COVID-19.

The vaccine is being developed by SK Bioscience in collaboration with the Institute for Protein Design at the University of Washington, with $213 million funding from the Gates Foundation and CEPI as part of the 'Wave 2' vaccine investment project to develop more accessible and affordable COVID-19 vaccines.

Results from the phase III study are expected in the first half of 2022.

Delta variant doubles the risk of being admitted to hospital with COVID-19

People infected with the SARS-CoV-2 Delta variant that is now causing most infections across Europe and the rest of the world have approximately double the risk of hospitalisation compared with those infected with the Alpha variant that was dominant from December to May, according to a study of more than 40,000 cases from England between 29 March and 23 May 2021, published in The Lancet Infectious Diseases.

Around one in 50 patients in the study was admitted to hospital within 14 days of their first positive COVID-19 test. After accounting for factors that are known to affect susceptibility to severe illness from COVID-19, including age, ethnicity, and vaccination status, the researchers found the risk of being admitted to hospital was more than doubled with the Delta variant compared with the Alpha variant.

The study is the first to report hospitalisation risk for the Delta versus Alpha variants based on cases confirmed by whole genome sequencing, which is the most accurate way to determine which variant is involved.

The Delta variant was first reported in India in December 2020 and early studies found it to be up to 50% more transmissible than the Alpha variant of COVID-19 that had previously gained dominance worldwide, after it was first identified in Kent, UK.

During the study period, there were 34,656 cases of the Alpha variant (80%) and 8,682 cases of the Delta variant (20%). While the proportion of Delta cases in the study period overall was 20%, it grew to account for around two thirds of new COVID-19 cases in the week starting 17 May 2021, indicating it had overtaken Alpha to become the dominant variant in England.

The study demonstrates the effectiveness of COVID-19 vaccines. Only 1.8% of people hospitalised with either variant had received both doses of a vaccine; 74% of cases were unvaccinated, and 24% had received one dose.

UK announces £4M for 5 COVID-19 projects in vaccine immunity and boosters

Five new UK COVID-19 research projects were announced on Thursday, which will receive a total of over £4 million from UK Research and Innovation, to study the durability of vaccine responses, low responses linked with health conditions, and the effect of booster doses.

The studies will research the strength and durability of the immune response in a wide range of people, including those with conditions that result in a weakened immune system, such as HIV, B cell lymphoma, inflammatory bowel disease and chronic myeloid leukaemia; people who are obese; healthcare workers; and people in the general population who have a weak immune response to vaccination.

The research aims to determine how long immunity from vaccination lasts; identify groups of people at risk from low vaccine responses; and determine if and when vaccine boosters are required for these groups, as well as the wider population.

One of the studies will potentially involve administering booster doses to participants with a low vaccine response and monitoring the effect it has on their immune systems.

Another study, conducted across the UK, South Africa and Brazil, will monitor immunity and vaccine effectiveness to virus variants.

Researchers in another study will monitor the effect the effect of different levels of weight loss on the immune response of 200 people with severe obesity, who are taking part in an existing weight loss study.

Rob Buckle, chief scientist of the Medical Research Council said vaccines have proved to be an invaluable tool in the fight against COVID-19, but there are still questions to be answered. “These studies will help provide guidance to policy makers and clinicians on a range of issues, including when and for whom booster shots are necessary,” Buckle said.

EMA approves new manufacturing site for BioNTech’s COVID-19 vaccines

The European Medicines Agency (EMA) gave approval for a new manufacturing site to start producing the Pfizer/BioNTech COVID-19 vaccine, a move that will increase capacity and supply of COVID-19 in the EU.

The facility in Saint Rémy sur Avre, France, operated by Delpharm and will manufacture finished product and is expected to supply an additional 51 million doses in 2021 alone.

EMA has also approved a new manufacturing line at BioNTech’s manufacturing site in Marburg, Germany. That will increase the capacity to manufacture the active substance that forms the basis of the vaccine by approximately 410 million doses in 2021.

In addition, EMA gave its stamp of approval to an additional US manufacturing facility for Moderna’s COVID-19 vaccine, in Bloomington, Indiana.

These recommendations do not require a European Commission decision, which means the sites can produce vaccines for the EU market immediately.

ERC funded research shows mutation rate of Covid-19 virus 50% higher than thought

The SARS-CoV-2 virus that causes Covid-19 mutates almost once a week, significantly more than the rate estimated previously, according to a new European Research Council funded study by scientists at Edinburgh and Bath universities. They say their findings indicate that new variants could emerge more quickly than was thought.

SARS-CoV-2 was thought to mutate about once every two weeks, but this estimate overlooked many mutations that happened but were never sequenced. That is because they were so called negative mutations which don’t survive long enough to be sequenced and so are missing from calculations of the mutation rate.

Allowing for these missing mutations, the researchers estimate the true mutation rate of the virus is at least 50% higher than previously thought.

The researchers say their findings, published in the journal Genome Biology and Evolution, reinforce the need to isolate individuals with weakened immune systems who struggle to contain the virus.

Laurence Hurst, professor of evolutionary genetics at Bath University, said, “With the great number of genomes of SARS-CoV-2 now sequenced, we can say something about both how many and why these mutations are missing, despite the fact that we can’t fully study them directly.”

EU approves €108M aid for Danish vaccines company

The European Commission has approved a €108 million Danish aid measure for coronavirus-related research and development at vaccines specialist Bavarian Nordic, under the state aid temporary framework.

The public support will take the form of a repayable advance to support the development of a coronavirus vaccine in-licensed by Bavarian Nordic from two other Danish biotechs, which is currently in phase II clinical development. The money will fund the phase III trial to confirm safety and demonstrate efficacy, develop manufacturing processes, and work to secure regulatory approvals.

The Commission said the aid is in line with the temporary state aid framework. In particular, it will cover less than 80% of the R&D costs and will be fully recovered if the vaccine is approved.

Pfizer/BioNTech COVID-19 vaccine gets full US approval

German biotech BioNTech said the US Food and Drug Administration has granted a licence to its COVID-19 vaccine Comirnaty, replacing the emergency use authorisation currently in force.

That makes Comirnaty the first vaccine against SARS-Cov-2 to have been given full approval by the FDA.

The vaccine has been available in the US under emergency use authorisation since 11 December 2020, on the basis of initial data from the pivotal phase III clinical trial.

“While this and other vaccines have met the FDA’s rigorous, scientific standards for emergency use authorisation, as the first FDA-approved COVID-19 vaccine, the public can be very confident that this vaccine meets the high standards for safety, effectiveness, and manufacturing quality the FDA requires of an approved product,” said acting FDA Commissioner Janet Woodcock. “While millions of people have already safely received COVID-19 vaccines, we recognise that for some, the FDA approval of a vaccine may now instil additional confidence to get vaccinated,” she said.

For full approval, BioNTech and partner Pfizer submitted longer-term data from the phase III trial, based on the vaccine’s efficacy and safety profile up to six months after the second dose. After submission in May 2021 the file was granted priority review in July.

“Our companies have shipped more than one billion doses worldwide, and we will continue to work tirelessly to broaden the access to our vaccine and to be prepared for potential emerging escape variants,” said Ugur Sahin, CEO and co-founder of BioNTech

Pfizer and BioNTech now plan to seek FDA approval for a third, booster dose, of Comirnaty.

UK orders further 35M doses of Pfizer/BioNTech COVID-19 vaccine

Coinciding with the US Food and Drug Administration announcing full approval of Pfizer/BioNtech’s COVID-19 vaccine, the UK government said it placed an order for 35 million more doses, to be delivered from the second half of next year.

The order was described as part of preparations to futureproof the country from the threat of COVID-19 and its variants.

At present plans are being laid for a booster programme later this year, details of which are due to be announced in September.

The Department of Health said COVID-19 vaccines have saved 95,200 lives in the UK. Vaccination has also prevented 82,100 hospitalisations and 23.9 million infections in England, according to the latest data.

Israeli company gets European approval for COVID-19 severity test

MeMed Ltd has received the CE Mark in Europe for its new diagnostic MeMed COVID-19 Severity, a 15 minute test to assess which patients arriving in accident and emergency with COVID-19 infections are likely to progress to severe disease.

The test measures multiple proteins from a blood sample and applies machine learning to stratify the risk that a patient with COVID-19 disease is likely to experience severe outcomes.

The test is designed to identify patients who will need escalated care and those who may be safely discharged from the hospital and instructed to self-isolate at home.

With the CE mark, Haifa, Israel-based MeMed can now commercialize the test to help identify COVID-19 patients at risk of severe outcomes, and enable clinicians to manage what is increasingly likely to become an endemic situation, said Eran Eden, MeMed’s co-founder and CEO. MeMed COVID-19 Severity is also relevant for authorities looking at preparedness for future pandemics.

“It is another exciting step in the company’s long-term vision of harnessing the power of the host-immune response in order to transform the way infections are detected and managed,” Eran said.

Helping it to reach this point, in 2015 MeMed was awarded a Horizon Europe grant of €3 million.

The company recently published the results from a multinational clinical study, demonstrating the ability of its test to accurately predict severe COVID-19 respiratory failure. MeMed has also completed an additional independent multinational validation study, with the results due to be published in the coming months.

“Highly sensitive and accurate diagnostic and prognostic tests are key tools for clinicians, said Sergey Motov, professor of Emergency Medicine at Maimonides Medical Centre in New York “As an ER doctor myself, I am fascinated by the potential for host immune response technologies to help predict patient outcomes.” With tools like MeMed COVID-19 Severity doctors can assess the likelihood of patients suffering from severe complications, enabling tailored treatments or discharge if the risk of deteriorating is low, Motov said.

New test could be used to self monitor COVID-19 antibodies over time

Researchers at Birmingham University have published an article demonstrating a new spike antibody lateral flow device is able to monitor antibody response following vaccination or natural infection with SARS-CoV-2 over time.

The paper shows differences in strength of antibody response with the Pfizer and AstraZeneca vaccines, and in the natural antibody responses to the original variant of the virus, first identified in Wuhan, China, around which the vaccines are designed.

The research also shows that these antibodies cross-react to the spike protein of different variants, such as the Delta variant that originated in India and which is now responsible for most infections in Europe.

The study was conducted using a lateral flow device called AbC-19TM LFD, developed by UK diagnostics specialist Abingdon Health. Unlike many of the lateral flow tests on the market, the test is designed to identify responses to different COVID-19 variants.

With the successful roll-out of vaccinations, it is now imperative to monitor the neutralising antibody levels in the worldwide population, to maintain the safety of the public and instil confidence in people as they return to normal life, said Chris Yates, CEO of Abingdon Health

“This study demonstrates how AbC-19TM can be used to monitor antibody response alongside vaccines, as well as the neutralising antibody response following natural infection. The AbC-19TM test will allow individuals to know their own status, which is becoming a growing concern, and allow healthcare agencies and healthcare professionals worldwide to manage the continued vaccination roll-out and to develop effective and targeted booster vaccination programmes,” Yates said.

In addition, the study also shows the ability of the company to change the format of the test if other variants of concern emerge that generate a different antibody response.

Next month, Abingdon intends to make a supplementary product available, initially for research use only, which provides a semi-quantitative result, indicating the strength of antibody response and possibly immunity.

Another COVID-19 vaccine on the way

The European Medicines Agency has started a rolling review of Sanofi Pasteur’s COVID-19 vaccine Vidprevtyn.

The decision to start the rolling review is based on preliminary results from laboratory studies and early clinical studies in adults, which suggest that the vaccine triggers the production of antibodies against the SARS-CoV-2 virus that causes COVID-19, and may help protect against the disease.

EMA says it will evaluate data as they become available, with the rolling review continuing until enough evidence is available for a formal marketing authorisation application.

The agency said it cannot predict the overall timelines, but should take less time than normal to evaluate an eventual application because of the work done during the rolling review.

Vidprevtyn is a protein-based vaccine that contains a laboratory-grown version of the spike protein found on the surface of SARS-CoV-2. It also contains an adjuvant to help strengthen the immune response to the vaccine.

Trade-related bottlenecks, not IP rights to blame for low access to COVID-19 vaccines in poorer countries

The World Trade Organisation published a list of trade related problems it says are to blame for limited access to COVID-19 vaccines in poorer countries, as it sat down with the World Health Organisation to discuss how to address the problem.

The private discussion, aimed to identify obstacles and propose solutions for increasing vaccine rates and bridging the wide gap in vaccination rates between rich and poor countries.

Participants described current and projected production volumes as well as plans for new investments in production capacity. They shared experiences about specific supply chain bottlenecks they were encountering, from export restrictions and raw material shortages and onerous regulatory processes, and exchanged ideas on how these might be addressed.

They also discussed issues around the transfer of know-how and technology, as well as factors influencing decisions on licensing intellectual property.

While there was broad agreement on the importance of keeping supply chains open and predictable, different perspectives were expressed on the proposed waiver of the WTO's Trade-Related Intellectual Property Rights Agreement in relation to vaccines and other products needed to combat COVID-19.