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Two new studies add to evidence that SARS-CoV-2 jumped to humans at the Wuhan seafood market

Two studies published in the journal Science use complementary approaches, involving spatial, environmental and molecular analyses, to provide evidence that the Huanan seafood market in Wuhan, China, was the early epicentre for the COVID-19 pandemic.

The scientists conclude it was very likely that SARS-CoV-2 was present in live mammals sold at this market in late 2019 and suggest the virus spilled over into people working or shopping there from two separate zoonotic transmissions, in which lineage A and B progenitor viruses were both circulating in non-human mammals prior to their introduction into humans.

The authors of both studies say future research should be focused on better understanding events preceding of the introduction of SARS-CoV-2 to the market, including where the wild mammals for sale at Huanan came from, to lower the risk of future pandemics.

Despite the observation that most of earliest known COVID-19 cases that were flagged by hospitals in Wuhan in December 2019, were linked to the Huanan market, this did not definitively establish the market as the trigger for the pandemic.

Indeed, two authors named on both of the papers had previously said they thought the pandemic could have been sparked by the accidental release of the virus from the Wuhan Institute of Virology.

Both say their opinions have changed as result of detailed re-analyses of data collected immediately after the initial outbreak in Wuhan.

“While the exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China, and show that the Huanan market was the epicentre of the COVID-19 pandemic,” concludes the paper which re-examined epidemiological data.

To test the hypothesis the market was the epicentre as the pandemic’s epicentre, the researchers used mapping tools to estimate the longitude and latitude locations of more than 150 of the earliest reported virus cases from December 2019, including those without reported direct links to the market.

The highest density of these early cases centred around the Huanan market. Then, by mapping cases from January and February 2020 using data from the social media app Weibo, which had set up a channel for people with COVID-19 to seek medical help, the researchers identified cases in other parts of central Wuhan radiating from the market as the pandemic progressed.

Using social media data, the researchers ruled out the many other locations in Wuhan, a city of 11 million, that would have been equally or more likely than the market to sustain the first cluster of a new respiratory pathogen.

They also had access to data showing multiple plausible intermediate animal hosts of SARS-CoV-2 progenitor viruses were sold live at the Huanan market until at least November of 2019. Using data from swabs taken from surfaces in the market, the researchers identified five market stalls that were likely to have been selling live or freshly butchered mammals. The proximity to such live mammal vendors was predictive of human virus cases.

Further increasing understanding of the pandemic's origin, the second paper reports an analysis of the genomic diversity of SARS-CoV-2 early in the pandemic.

While the diversity of SARS-CoV-2 increased as the pandemic spread from China to other countries, two lineages of SARS-CoV-2 – designated A and B – marked the beginning of the COVID-19 pandemic in Wuhan.

Only lineage B was represented in the eleven sequenced genomes from humans directly associated with the Huanan market, while the earliest lineage A genomes from humans lacked any known contact to the market, but were sampled from humans who lived close by.

It has been hypothesised that the two lineages emerged separately and this was confirmed by the analysis, with lineage B first appearing in humans no earlier than late October 2019 and likely in mid-November 2019, and lineage A being introduced within days to weeks of this event.

These findings indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported, the researchers say.

New research advances the prospect of a COVID-19 vaccine that protects against all variants

Researchers at the Francis Crick Institute in London have shown that a specific part of the SARS-CoV-2 spike protein is a promising target for a pan-coronavirus vaccine that could offer some protection against new virus variants and the common cold - and help prepare for future pandemics.

As the latest wave of COVID-19 infections caused by the Omicron variant demonstrates, the frequent mutations seen in the SARS-Cov-2 virus is undermining the level of protection provided by vaccines that were designed to combat the original virus that emerged in Wuhan, China.

These existing vaccines trigger antibodies against the S1 sub unit of the spike protein via which SARS-CoV-2 latches on to human host cells.

There has been little attention to the S2 subunit of the spike protein, despite the fact that its structure is similar across a number of coronaviruses, and that it is less subject to mutating.

The Crick researchers investigated whether antibodies that target the S2 subunit would also neutralise other coronaviruses. Mice vaccinated with a vaccine against S2 generated antibodies that were able to neutralise a number of other animal and human coronaviruses, including the seasonal common cold coronavirus, the original Wuhan strain of SARS-CoV-2; the D614G mutant that dominated in the first wave; the Alpha, Beta, Delta and BA-1 and BA.2 Omicron variants; and two bat coronaviruses.

“The S2 area of the spike protein is a promising target for a potential pan-coronavirus vaccine because this area is much more similar across different coronaviruses than the S1 area,” said Kevin Ng, of the Crick’s Retroviral Immunology Laboratory at the Crick. “It is less subject to mutations, and so a vaccine targeted at this area should be more robust.”

The expectation for a vaccine that targets S2 is that it could offer some protection against all current, as well as future, coronaviruses. This differs from vaccines that target the more variable S1 area which, while effective against the matching variant they are designed against, are less able to target other variants, or a broad range of coronaviruses.

The S2 sub unit of the spike protein has, until recently, been overlooked because certain critical targets are only revealed after the virus has bound to a cell. As a result, there may be a narrower window of opportunity for S2 antibodies to neutralise the virus than is the case for antibodies that target the S1 sub unit.

While a potential S2 vaccine would not stop people being infected, the idea is it would prime their immune system to respond to a future coronavirus infection. This would hopefully provide enough protection to survive an initial infection during which they could develop further immunity specific to that particular virus.

The researchers say they are continuing to study the potential of a pan-coronavirus that targets the S2 area of the spike protein and how it could be integrated with licenced vaccines.

EMA’s Emergency Task Force starts review of sabizabulin for treating COVID-19

The European Medicines Agency has started to review the data for a potential new treatment for COVID-19 in advance of the manufacturer applying for marketing approval.

The drug, sabizabulin has shown a beneficial effect in a study involving hospitalised patients with moderate-to-severe COVID-19 who were at high risk of acute respiratory distress syndrome and death, with the results indicating it reduces deaths compared to placebo.

Although the developer, US biotech Veru, has not applied for marketing approval or a rolling review, EMA’s assessment is intended to inform member states which are considering use of sabizabulin before authorisation.

This review is the first to be triggered under the new EU regulation that expanded the role of EMA during public health emergencies.

Sabizabulin works by disrupting microtubules, which form part of the internal skeleton in cells. These microtubules play a role in helping SARS-CoV-2 enter and leave human host cells. By binding to parts of the microtubules, sabizabulin limits the replication and spread of the virus.

Sabizabulin is also expected to supress some inflammatory responses that occur following infection with SARS-CoV-2, including reactions that can lead to acute respiratory distress syndrome and death.

The review of sabizabulin was started on 27 July 2022 following a request from Germany.

Third booster dose of COVID-19 vaccine is crucial in protecting against new variants

Twenty-one different COVID-19 variants were effectively neutralised after a third booster dose of COVID-19 vaccine, according to a new UK study.

While the results indicate that immunity from infection by the SARS-CoV-2 virus decreases 20 weeks after receiving two doses of vaccine, a third booster dose, in this case of the Pfizer/BioNTech vaccine, revived the immune system, enabling to neutralise 21 different variants.

The researchers used an antigenic map developed by scientists at Surrey University, to measure how each variant impacted the immune system.

They analysed 72 blood samples from 37 individuals, aged 70 – 89 years, vaccinated with two doses of Pfizer/BioNTech vaccine, for neutralising antibody responses to the original strain of SARS-CoV-2 that was first detected in Wuhan, China.

Between 3 and 20 weeks after the second vaccine dose, neutralising antibody levels fell 4.9-fold to a median of 21.3, with 21.6% of individuals having no detectable neutralising antibodies at the later time point.

Next, the researchers examined neutralisation of 21 distinct SARS-CoV-2 variant spike proteins by these blood samples and confirmed there was substantial antigenic escape, especially for the Omicron, Delta and Beta variants.

However, following administration of a third booster dose, neutralising antibody levels increased, providing cross-protection against Omicron BA.1 and BA.2. The researchers say that despite SARS-CoV-2 immunity waning over time in older adults, booster vaccines are able to elicit broad neutralising antibodies against a large number of SARS-CoV-2 variants in this clinically vulnerable cohort.

"Understanding how the levels of neutralising antibodies relate to a well-defined immune response will be an important step in understanding how the immune system responds to SARS-CoV-2 and could also help in the management of COVID-19,” said researcher Dalan Bailey.

"This information could help us to understand whether the risk of breakthrough infections, hospitalisation and death is increased by waning immunity or new variants. Research comparing immune responses to different SARS-CoV-2 variants and understanding the role of different mutations is vital,” Bailey said.

German study points to limited antibody response to Omicron variants of SARS-CoV-2

The viral spike protein by which SARS-CoV-2 enters human cells has changed at more than 50 sites in the Omicron variant that is causing the current wave of infections, compared to the original virus first identified in Wuhan, China.

As a consequence, the antibodies formed after an infection or vaccination do not recognise these variants as efficiently. That means despite having overcome an infection, people can again become infected with the Omicron variant, and that there are breakthrough infections in people who are vaccinated.

Researchers in Frankfurt headed by Marek Widera and Sandra Ciesek from the Institute for Medical Virology at the University Hospital of the Goethe University, have examined how long antibodies present in blood after a vaccination or recovery from an infection are able to neutralise the virus variants Omicron BA.1 and BA.2.

They collected blood samples from people who had been vaccinated twice or three times.

Six months after the second vaccination, the blood samples had practically no neutralising effect on the Omicron variants BA.1 and BA.2.

The effect of a booster vaccination also declined rapidly. Although there was very good protection shortly after the booster vaccination, three months later the protective effect was very weak and the samples were no longer capable of neutralising BA.1 and BA.2.

The in vitro data does not allow any conclusions to be drawn about the severity of COVID-19, because it takes no account of the cellular immune response.

However, the results do pose a problem for the use of monoclonal antibodies as a precautionary measure in patients with compromised immune systems. For three such monoclonal antibodies studied in the lab, the level of efficacy was very heavily dependent on the virus variant.

Large-scale UK study pinpoints symptoms of Long COVID that continue more than 3 months after infection

SARS-CoV-2 has been associated with a range of symptoms in the immediate aftermath of infection, but now a retrospective UK study has catalogued previously reported and new symptoms non-hospitalised adults are suffering from more than three months after infection, and the risk factors associated with developing these persistent symptoms.

The researchers at Birmingham University matched the primary care records of 486,149 adults with confirmed SARS-CoV-2 infection, to the records of 1,944,580 adults with no recorded evidence of SARS-CoV-2 infection.

The outcomes included 115 individual symptoms, as well as Long COVID, which is defined as a composite outcome of 33 symptoms by the World Health Organisation clinical case definition.

A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest associations were for anosmia (loss of smell), hair loss, sneezing, ejaculation difficulty and reduced libido.

Among the cohort of patients infected with SARS-CoV-2, risk factors for Long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities.

A key strength of the study is the large sample size. This provided the statistical power to assess differences in the reporting of a wide range of symptoms between the two cohorts and estimation of the association between reporting of symptoms and important sociodemographic and clinical risk factors with a high level of precision, the researchers say

New test speeds up assessment of T-cell responses to COVID-19

Researchers at the Medical University of Vienna have developed a blood test that measures cellular T-cell immunity to SARS-CoV-2 in just 48 hours. That compares to the current test which takes up a week to process.

They say the test will be particularly relevant for assessing the immune status of vulnerable patients, whose weakened immune systems mean they do not mount a meaningful antibody response.

Using the test, it is possible to tell if immunity is the result of vaccination or natural infection.

The new test is based on the memory response of T cells to three different mixtures of peptides from COVID-19 patients.

T cells are an important part of the specific cellular immune defence, eliminating cells that are infected with SARS-CoV-2 and supporting antibody production by B cells. "Currently, it takes at least a week to perform and evaluate such T-cell tests, and the tests can only be performed in specialised laboratories. In contrast, our newly developed test is performed directly with a whole blood sample and can be evaluated after only 48 hours," said study leader Winfried Pickl.

In the study, T-cell responses were measured at ten weeks and ten months after infection with SARS-CoV-2. It was shown that T-cell responses were as strong at ten months, as at ten weeks after an infection.

The researchers say this is remarkable because antibody levels dropped significantly ten months after infection. This long-lasting T-cell response may protect against severe disease in the event of re-infection with SARS-CoV-2.

Real world data from seven million adults shows COVID-19 vaccines give high protection for up to six months

Protection against severe COVID-19 provided by two doses of the Pfizer/BioNTech or AstraZeneca COVID-19 vaccine remained high up to six months after second doses, according to an analysis of health record data of over seven million adults in the UK.

The study found that protection was maintained in older adults aged over 65 years, and in clinically vulnerable adults.

Using linked general practitioner, hospital, and COVID-19 records on 1,951,866 adults who had received two doses of Pfizer/BioNTech, 3,219,349 adults who had two doses of AstraZeneca vaccine and 2,422,980 people who were unvaccinated, researchers were able to provide a clearer picture of vaccine effectiveness against COVID-19 hospital admission, COVID-19 death, and a positive SARS-CoV-2 test.

Rates of COVID-19 hospital admission and COVID-19 deaths were substantially lower among vaccinated than unvaccinated adults up to six months after their second dose. Vaccine effectiveness was at least 80% for Pfizer/BioNTech, and at least 75% for AstraZeneca.

But while protecting against severe disease, waning vaccine effectiveness against infection with SARS-CoV-2 meant that vaccinated people were about as likely to get infected as people who were unvaccinated by six months after the second dose.

Elsie Horne, senior research associate in medical statistics at Bristol University’s Medical School, the study’s lead author, said, “Until now there has been limited and conflicting evidence relating to the rate of waning following second dose of COVID-19 vaccines, whether it extends to severe COVID-19, and whether the rate differs according to age and clinical vulnerability.”

“Although we found that protection against severe COVID-19 provided by two doses of vaccine wanes over time, the very high initial protection means that, despite waning, protection remains high six months after the second dose. This finding was consistent across all adults, including older adults and those who are at risk of severe COVID-19.”

The rate at which vaccine effectiveness waned was consistent across subgroups defined by age and clinical vulnerability.

Studying how long COVID-19 vaccines is important for scheduling and targeting of booster vaccinations.

The researchers now plan a follow-up study looking at vaccine effectiveness up to one year post-second dose, and against Omicron variant.

Commission reduces order for Valneva COVID-19 vaccine from 60M to 1.25M doses

European Commission has cut its order for Valneva’s whole-virus COVID-19 vaccine, VLA2001, from 60 million to 1.25 doses, with the option to purchase an equivalent quantity later this year for delivery in 2022.

The first vaccine doses will be delivered to Germany, Austria, Denmark, Finland and Bulgaria in the coming weeks.

Valneva is late to the party, with its product only receiving approval in June, but the company was hoping that as a traditional whole virus vaccine, it would find a niche market in people who chose not to be vaccinated with mRNA or viral vectored vaccines.

Thomas Lingelbach, CEO of Valneva said, “We welcome the fact that the European Commission has decided not to terminate the advance purchase agreement, although we feel the order volume does not reflect the interest we see from European citizens. Despite this, we have decided to enter into this amendment to make our vaccine available to the Europeans who have been waiting for it. “

While the pandemic had been declining, the latest COVID-19 wave in Europe clearly underlines the need for alternative vaccines, Lingelbach said. “Fifteen per cent of Europeans over 18 are not yet vaccinated and we continue to receive messages from Europeans who are awaiting a more traditional vaccine technology. Recent market studies conducted in several EU member states suggest that making our inactivated vaccine available in Europe could increase vaccine uptake and have a meaningful impact on public health.”

VLA2001 is the first COVID-19 vaccine to receive a standard marketing authorisation, as opposed to emergency use authorisation in Europe.

Non-invasive skin swabs could be new way to test for COVID-19

Skin swabs have been shown to be "surprisingly effective" at identifying COVID-19, pointing the way to a non-invasive diagnostic test.

Researchers at Surrey University used swabs to collect sebum, the oily, waxy substance produced by the sebaceous glands, from 83 hospitalised patients, some of whom were diagnosed with COVID-19. They also collected blood and saliva samples for this comparative study.

Melanie Bailey, co-author of a paper describing the research said, "COVID-19 has shown us that rapid testing is vital in monitoring and identifying new illnesses. In our research, we explored the relationships between different biofluids, and what changes in one part of the human body can tell us about the overall health of a patient.”

Blood was the most accurate way of testing for the virus, but skin swabs were not too far behind “In fact, the skin swab results were surprisingly accurate," Bailey said.

COVID-19 significantly change the makeup of lipids in biofluids such as blood and sebum.

By measuring changes in lipids and other metabolites of the samples, the research team observed that blood samples scored 0.97 of a possible 1.0, while skin swab tests scored 0.88, and saliva tests 0.80.

Matt Spick, a co-author said, “Our research suggests that skin sebum responds to changes to the immune system in COVID-19 patients. In fact, we believe that illness can alter the body’s natural balance across the whole range of biological systems, including skin, digestive health and others.

New warning from WHO as COVID-19 cases rise across Europe

New WHO/Europe guidance published today urges countries to urgently address gaps in pandemic monitoring and response to avoid preventable deaths and severe disruption to healthcare systems.

Hans Kluge, WHO Regional Director for Europe says it is now “abundantly clear” Europe is in a similar situation to last summer, when COVID-19 infections were on the rise. The latest wave is being propelled by sub-lineages of the Omicron variant, notably BA.2 and BA.5, with each dominant sub-lineage of Omicron showing clear transmission advantages over the previously circulating viruses.

The European Region has seen a tripling of new COVID-19 cases over the past 6 weeks, with close to three million new cases reported last week, accounting for nearly half of all new cases globally. While hospitalisation rates due to COVID-19 have doubled in the same period, intensive care unit admissions have so far remained relatively low.

However, as infection rates in older groups continue to rise, Europe is still seeing close to 3,000 people die of COVID-19 every week.

“With rising cases, we’re also seeing a rise in hospitalisations, which are only set to increase further in the autumn and winter months as schools reopen, people return from holidays and social mixing moves indoors with the onset of colder weather. This forecast presents a huge challenge to the health workforce in country after country, already under enormous pressure from dealing with unrelenting crises since 2020,” Kluge said.

WHO/Europe is released its autumn/winter strategy for COVID-19 and other respiratory viruses to help prepare for the coming waves of infection. “Waiting for the autumn to act will be too late,” said Kluge. 

The strategy calls on countries to relaunch mitigation efforts and be ready to respond to an increased burden on their healthcare systems.

“More than two years into the pandemic, we’re all aware of the tools we have to keep ourselves safe, assess our level of risk and take the necessary steps to protect others if we get infected,” Kluge said.

Blowing in the wind: instruments could spread SARS-CoV-2

As with coughing, sneezing, talking and singing, playing wind instruments – particularly those in the brass section – can spread respiratory particles that may carry the SARs-CoV-2 virus.

Early in the pandemic, engineers at Colorado State University, led by John Volckens teamed up with musicians to try and quantify respiratory particle emissions from music-playing.

The researchers used an aerosol measurement chamber and recruited volunteers to perform in the chamber while aerosol emissions from the musicians and their instruments were analysed. The 81 volunteers played wind instruments including the bassoon, clarinet, French horn, oboe, piccolo, saxophone, trombone, trumpet and tuba.

Brass instruments on average, produced 191% more aerosols than woodwinds. The researchers’ highest particle counts of brass playing were even higher than their highest results from singers in a previous study, by nearly a factor of four.

Being male was also associated with a 70% increase in emissions from instrument-playing, probably due to lung size and capacity. Louder playing of brass instruments was associated with higher particle counts, but louder playing of woodwinds did not increase emissions.

The researchers also took measurements with performers using bell covers in an attempt to mitigate the particle spread, which seemed to work. The use of the covers reduced emissions from trombone, tuba and trumpet players by an average of 53-73%, but not from the oboe or clarinet.

Volckens, a mechanical engineer and aerosols expert, likened bell covers to blue surgical masks for instruments – good, but not great in terms of limiting spread.

“The data suggest that masks and bell covers cut down half to 75% of particles coming out of the mouth or instrument,” Volckens said. “And the reason blue surgical masks or bell covers don’t work better is that they’re just not a tight fit.”

The researchers say this study, and previous ones like it, confirm that the start of the pandemic, particularly before the advent of vaccines, shutting down performing arts in the name of safety is likely to have saved lives.

Real world data show AstraZeneca COVID-19 vaccine as effective as mRNA rivals

An expert review of data from 79 real-world studies has shown that AstraZeneca’s COVID-19 vaccine, Vaxzevria, provides equally effective protection against hospitalisation and death from COVID-19 following two doses, as do the mRNA vaccines that have dominated vaccination programmes in Europe.

Data on vaccine use and impact, collated by Johns Hopkins University and the International Vaccine Access Centre, was reviewed by infectious disease experts from across Asia. The study findings are published in Expert Review of Vaccines.

The analysis shows Vaxzevria and Pfizer/BioNTech and Moderna’s COVID-19 vaccines offer an equivalent degree of protection against hospitalisation (91-93%) and death (91-93%), regardless of age.

The data available at the time of review relates to the Delta SARS-Cov-2 and earlier variants. However, emerging data on third dose boosting from the UK Health Security Agency and Brazil indicate similar findings on serious COVID-19 outcomes resulting from the Omicron variant that is currently rife.

Guy Thwaites, director of the Oxford Clinical Research Unit in Vietnam and one of the study’s authors, said, “Our expert review shows that Vaxzevria and available mRNA vaccines provide similar, high-level protection against life-threatening COVID-19. This is important information for policymakers as they consider the optimal deployment of COVID-19 vaccines in their populations over the next 12 months.”

John Perez, senior vice president, head of th late development vaccines unit, AstraZeneca said, “We are pleased that these data continue to show high-levels of protection against severe clinical outcomes and further our understanding of the important role that vaccination plays in the containment of COVID-19.”

While it started out level pegging with the mRNA vaccines, the popularity of Vaxzevria plummeted after reports of adverse events showed that unusual blood clots with low blood platelets are a rare side effect. The European Medicines Agency said a warning to that effect should be added to the label.

The Johns Hopkins database is updated on a weekly basis to include global real-world studies on vaccine effectiveness, but it is not currently designed to capture the safety outcomes of these studies, preventing safety comparisons between different types of vaccines.

Unlike Pfizer/BioNTech and Moderna, AstraZeneca widely licensed the Vaxzevria intellectual property and transferred the manufacturing knowhow to manufacturers around the world in low an from the very early days of development getting underway. The company’s partners have released over three billion vaccine doses to more than 180 countries, and approximately two thirds of these doses have been delivered to low and lower-middle income countries.

Based on modelling of outcomes, Vaxzevria is estimated to have helped save over six million lives between 08 December 2020 and 08 December 2021.

Being born during the pandemic has no effect on behaviour, Swiss researchers report

Researchers at the University of Zurich (UZH) who have studied whether infants born during the pandemic exhibit different social behaviour from same-aged infants before the pandemic, conclude they do not seem to be developing any differently.

They reached this conclusion by assessing the children’s ability to follow another person’s gaze.

“This ability is fundamental for engaging in social interactions, building relationships and developing language skills,” said Stephanie Wermelinger, who researches developmental psychology in infants and children in the department of psychology at UZH. If this ability is impaired, it can hamper a person’s ability to interact with society, as is the case for people with autism.

Eighty infants between the age of 12 and 15 months took part in the study. They were shown different videos in which a person was gazing at one of two objects. By tracking the infants’ eye movements, the researchers recorded how often and how quickly the infants followed the person’s gaze. They then compared their data with eye movement data from 133 children using the same method before the pandemic.

There were no significant behavioural differences between the children born during and before the pandemic. Children born during the pandemic followed the person’s gaze just as often and quickly as the children in the pre-pandemic group.

That is despite the pandemic meaning the children in the study saw fewer people overall and interacted with more people who were wearing masks. They do not seem to be developing any differently from children who didn’t experience those pandemic-related changes, the researchers say.

“We believe the unchanged social interactions with parents and caregivers at home are enough to mitigate any influence the COVID-19 pandemic might have had on infants,” Wermelinger said.

Moderna's Omicron-containing COVID-19 vaccine more effective than original

Moderna has announced its bivalent vaccine mRNA-1273.214, which is designed against both the original Wuhan strain of SARS-CoV-2 and the Omicron variant, has demonstrated significantly higher antibody titers against all tested variants of the virus, including Omicron BA.1 and the BA.4 and BA.5 subvariants, and their forerunners, Alpha, Beta, Delta, and Gamma.

The company has filed for approval in Europe and said it expects to complete most filings elsewhere this week.

One month after administration in previously vaccinated and boosted participants, a booster dose of mRNA-1273.214 elicited significantly higher levels of neutralising antibody responses against the Omicron subvariants BA.4, and BA.5 which currently is causing a new wave of infections in Europe, compared to Moderna’s original vaccine. The effect was seen regardless of prior infection status or age.

This latest update adds to the largest body of data confirming the superiority of a bivalent approach, said Stephane Bancel, CEO of Moderna. “This superior breadth and durability of immune response following a bivalent booster has now been shown in multiple Phase II/III studies involving thousands of participants," he said.

The mRNA-1273.214 bivalent booster is the only modified COVID-19 vaccine expected to have demonstrated significantly higher titres against Omicron BA.4 and BA.5 in a clinical trial before the autumn booster season.

“It was always a given that the first generation of these vaccines would require modifications, however, unfortunately we are always a step behind the virus evolution,” said Beate Kampmann, director of the Vaccine Centre at the London School of Hygiene and Tropical Medicine, reacting to the Moderna data. “Unfortunately we are always a step behind the virus evolution. We ultimately need to get to a space where models might predict what happens next, so we can get ahead of the curve.”

The question of who needs a booster is a bit of a moving target too. “We are now facing a mix of community immunity and personal protection induced by vaccines or natural infection - and most likely both. In the absence of a personalised vaccination approach, able to use correlates of protection to predict who is protected for how long, and against what COVID-disease manifestations, we need to stick with the notion of trying to protect the most vulnerable people with adapted boosters,” Kampmann said.

Curevac files claim BioNTech/Pfizer COVID-19 vaccine infringes its mRNA patents

German biotech Curevac has filed a lawsuit against its counterpart BioNTech, claiming the COVID-19 vaccine co-developed with Pfizer infringes four of Curevac’s mRNA patents.

While moving to assert its rights, CureVac said it is not seeking an injunction nor does it intend to take legal action that impedes the production, sale or distribution of the vaccine by BioNTech and Pfizer.

Rather, in the lawsuit filed in the German Regional Court in Düsseldorf against BioNTech and two of its subsidiaries, Curevac is seeking fair compensation for infringement of a portfolio of intellectual property rights it says BioNTech used in the manufacture and sale of the vaccine, Comirnaty.

The patents in question relate to the engineering of mRNA molecules, including sequence modifications to increase stability and enhance protein expression, as well as mRNA vaccine formulations specific to SARS CoV-2 vaccines, according to Curevac.

In response, BioNTech said it, “values and respects valid intellectual property rights,” but the work is original. “We will vigorously defend it against all allegations of patent infringement. However, we are aware that it is not unusual that other companies in the pharmaceutical industry, having witnessed the success of Comirnaty are now suggesting that the vaccine potentially infringes their intellectual property rights,” BioNTech said.

Before the pandemic struck, both companies were applying mRNA to develop cancer vaccines. They pivoted to developing COVID-19 vaccines when the pandemic took hold, with BioNTech forming its partnership with Pfizer on the back of an existing research collaboration between the two in influenza.

Curevac gave up on its first mRNA-based COVID-19 vaccine due to lack of efficacy, but now has another one it is co-developing with GlaxoSmithKline.

EMA recommends fourth dose of COVID-19 vaccine for people at risk and the over 60s

European Centre for Disease Prevention and Control (ECDC) and the European Medicines Agency (EMA) are recommending that second booster doses of mRNA COVID-19 vaccines be considered for people between 60 and 79 years old and people with medical conditions putting them at high risk of severe disease.

This follows on from the recommendation in April 2022 that people over 80 years of age be considered for a second booster. At that time EMA said it might be necessary to consider second boosters in people between 60 and 79 years old and vulnerable persons of any age if there was a resurgence of infections.

With a new wave of infections driven by the Omicron variants BA.4 and BA.5 now underway in Europe, with increasing rates of hospital and intensive care unit admissions, EMA says it is “critical” that public health authorities in member states now consider people between 60 and 79 as well as vulnerable persons of any age for a second booster.

These could be administered at least four months after the previous one, with a focus on people who have received a previous booster more than 6 months ago.

Stella Kyriadkides, European Commissioner for Health said there is no time to lose. “I call on member states to roll-out second boosters for everyone over the age of 60 as well as all vulnerable persons immediately and urge everyone eligible to come forth and get vaccinated.”

“We are currently seeing increasing COVID-19 case notification rates and an increasing trend in hospital and ICU admissions and occupancy in several countries mainly driven by the BA 5 sublineage of Omicron,” said Andrea Ammon, director of ECDC.

This signals the start of a new, widespread COVID-19 wave across the EU. “There are still too many individuals at risk of severe COVID-19 infection whom we need to protect as soon as possible […] We have to start today.”

At the moment, there is no clear evidence to support giving a second booster dose to people below 60 years of age who are not at higher risk of severe disease. Neither is there clear evidence to support giving early second boosters to healthcare workers or those working in long-term care homes, unless they are at high risk.

However, residents at long-term care homes are likely to be at risk of severe disease and should be considered for booster doses in line with national recommendations.

The latest ECDC/EMA advice comes amid work to adapt vaccines for the Omicron variants of concern.

“We are working towards possible approvals of adapted vaccines in September,” said EMA’s executive director, Emer Cooke. “Our human medicines committee is currently reviewing data for two adapted vaccines.”

Further details about the latest advice on second booster doses is in the ECDC/EMA joint statement.

New global hub set up to use genome sequencing to track SARS-CoV-2 and other infectious pathogens

A new global hub for genomic surveillance launched by the Wellcome Sanger Institute will work with partners around the world to use genome sequencing to help tackle infectious diseases.

The Genomic Surveillance Unit (GSU) will help partners to develop their own genomic surveillance capabilities, enabling them to generate information about infectious pathogens in circulation and their characteristics.

The surveillance will involve sequencing the genomes of pathogens to track evolutionary changes that affect transmission, disease severity and susceptibility to treatment.

The use of genomics for surveillance was very much in its infancy before the outbreak of the COVID-19 pandemic, having largely been used to map the emergence of antimicrobial resistance.

The technique has gained widespread visibility during the pandemic, with sequencing of SARS-CoV-2 viral genomes providing an invaluable tool to track the spread of the virus and emergence of new variants.

The mission of the GSU is to accelerate the generation of genomic data on a large scale. It will do this by working with partners to implement scientific pipelines, from sample collection through to the delivery of data. In particular, the unit will focus on strengthening capacity for the generation and sharing of genomic data, developing easy-to-use tools and methods, and creating accessible resources that provide actionable information for public health.

Mike Stratton, director of the Sanger Institute, said, “It is critical that the lessons learned and extraordinary experience acquired during the COVID-19 pandemic are not lost, but rather used to drive forward the development of effective genomic surveillance across the globe.”

While truly worldwide infectious disease genomic surveillance networks would be a huge boost to global health capability and pandemic preparedness, the cost and complexity of such programmes can be prohibitive. Making genomics more accessible and easier to scale will be vital if its potential as a practical tool for infectious disease control is to be realised for all.

John Sillitoe, director of the GSU said, “We are passionate about working with our partners to achieve their vision for integrating genomic surveillance into their scientific and public health infrastructure.”

New UK/US consortium to design and test vaccine that protects against all SARS-CoV-2 variants

A new consortium has been formed to design a vaccine that is effective against both SARS-CoV-2 and a number of related bat viruses that have the potential to spread to humans.

The project builds on technologies developed by the Molecular Immunology Group at Oxford University, a group based at Caltech in the US, and by researchers at the UK Medical Research Council’s Human Immunology Unit.

The Coalition for Epidemic Preparedness Innovations (CEPI), will partner with the consortium and has announced up to $30 million to fund preclinical studies, manufacturing and a phase I trial.

In contrast to a number of the existing COVID-19 vaccines that use mRNA or a viral vector to present sections of the spike protein of the virus that emerged in Wuhan, China, to the immune system, the new vaccine will use protein nanoparticles loaded with antigenic sections of the spike proteins from eight different viruses, held together by a molecular ‘glue’. It is hoped that will generate immune responses to the shared parts of each of the different types of coronaviruses within a single vaccine.

There also is evidence that indicates this approach will not only elicit protective immune responses against SARS-like viruses but also against some coronaviruses not presented in the trial vaccine. There is a suggestion that could provide protection against future novel SARS-CoV-2 variants and other coronaviruses with the potential to spill over from animal populations.

The Oxford lead of the consortium, Alain Townsend, professor of molecular immunology said, “The evolution of this consortium is an example of collaborative science at its best. We had been deeply impressed by the power of the ‘glue’ for sticking proteins together. Together we used this technology to make a prototype nanoparticle SARS-CoV-2 vaccine that induced highly potent responses in preclinical studies.”

New pandemic sciences institute will apply lessons of COVID-19 to prepare for future disease outbreaks

A new Pandemic Sciences Institute opened its doors at Oxford University this week, to take forward the lessons and experience of responding to COVID-19 in countering future pandemic threats.

The Institute will harness the university’s research and global research collaborations and partnerships developed over decades between academia and industry. Although based in the medical faculty it will draw together researchers from across the Oxford University, including veterinary sciences and social sciences. The work it carries out will span from basic science to implementation of interventions.

The director of the institute is Peter Horby, professor of Emerging Infections, who led the UK Recovery trial, which amongst other advances found the steroid dexamethasone is an effective treatment for COVID-19. That was the first drug to be shown to have a therapeutic effect against the disease.

“During the COVID pandemic, diagnostic tests, drugs and vaccines were developed and deployed at speeds that were previously unthinkable, and we benefited from remarkable insights into epidemiology, biology and behaviour in near real time,” Horby said. “The Pandemic Sciences Institute aims to make such exceptional achievements routine and ensure the benefits are shared by all. We believe that we can make the world a safer place for everyone by uniting disciplines and sectors to tackle complex infectious disease threats together.”

Swiss scientists show why infection with earlier variants does not protect well against Omicron

In the current wave of COVID-19 there is a particularly high risk of reinfection by the newer Omicron variant of SARS-CoV-2.

To uncover the reason behind this, a team from the Centre for Emerging Viral Diseases of the University of Geneva and Geneva University Hospital analysed the antibody neutralisation capacity of 120 people infected with the original SARS-CoV-2 strain, or with one of its Alpha, Beta, Gamma, Delta, Zeta or Omicron (sub-variant BA.1) variants.

They found that unlike its predecessors, Omicron appears to be able to evade the antibodies generated by other variants. In people who have been vaccinated the neutralisation capacity is also reduced, but it remains far superior to natural immunity alone.

This could explain why Omicron is responsible for a net increase in vaccine break-through infections, but not serious disease and hospitalisation.

Isabella Eckerle, professor in the faculty of Medicine who led this work said, “Since the beginning of 2020, we have collected samples of the original virus and all its variants that appeared in Switzerland, even the rarest ones such as Gamma or Zeta. This makes it a comprehensive collection of samples from individuals with different infection backgrounds, collected according to an identical protocol.”

The research team took blood samples from 120 volunteers previously infected with one of the different variants, unvaccinated, or vaccinated and infected, either before or after vaccination. The aim was to determine how well antibodies generated during the first infection were able to neutralise the different variants of SARS-CoV-2.

“Omicron proved to be the most effective at evading pre-existing natural immunity, as well as, to a lesser extent, that induced by vaccination”, said Benjamin Meyer, researcher at the Centre for Vaccinology. Antibody levels against ancestral SARS-CoV-2 in vaccinated people are roughly 10 times higher than in people who have only developed post-infection immunity. Moreover, the combination of the two seems to maintain even higher and broader reactive antibody levels.

“Thus, Omicron can evade existing immunity and cause an infection, but hospitalisation and death due to COVID-19, even with Omicron, is still reduced after vaccination,” Meyer said.

Nevertheless, SARS-CoV-2 retains an astonishing ability to mutate, and the rate of mutation appears to be accelerating. “Vigilance is still required, especially as the epidemiological curves have been rising sharply since the appearance of BA.5, the most recent Omicron sub-variant,” said Eckerle.

Latest Omicron subvariants are less efficiently inhibited by antibodies

Infection with the "old" Omicron subvariants BA.1 and BA.2 is providing little protection against the SARS-CoV-2 subvariants BA.2.12.1 and BA.4, and the BA.5 subvariant that is causing a “summer wave” of COVID-19 cases in Germany and elsewhere in Europe, according to German researchers.

The Omicron subvariants BA.1 and BA.2 of the SARS-CoV-2 virus dominated the COVID-19 pandemic in early 2022, but in many countries these are now outcompeted by emerging subvariants BA.2.12.1, BA.4 and BA.5, with BA.5 being responsible for the current uptick of cases in Germany.

However, at present it is unclear whether these three new Omicron subvariants have acquired biological traits that allow for more efficient transmission, or whether they are less efficiently blocked by antibodies compared to the old Omicron subvariants BA.1 and BA.2.

A study by researchers at the German Primate Centre (DPZ) - Leibniz Institute for Primate Research together with colleagues from Hannover Medical School and Friedrich-Alexander-University Erlangen-Nürnberg shows that the Omicron subvariants BA.2.12.1, and especially BA.4 and BA.5 are less inhibited than their predecessors BA.1 and BA.2, by antibodies generated after vaccination or infection.

The researchers also showed that most of the approved therapeutic antibody drugs for treating COVID-19, either do not inhibit BA.2.12.1, BA.4 and BA.5 at all, or only do so with reduced potency.

The researchers found that of ten therapeutic antibodies studied only two were able to at least partially inhibit BA.2.12.1, BA.4, and BA.5 and that only Eli Lilly’s monoclonal antibody bebtelovimab efficiently blocked infection by all Omicron subvariants.

“These results confirm a trend that we have already seen in previous studies: Omicron subvariants are not appreciably inhibited by most therapeutic antibodies and the few antibodies that inhibit frequently do so in a subvariant-specific fashion. Therefore, it is important to develop new antibodies in order be prepared for future subvariants,“ said Prerna Arora, first author of the study.

In terms of the ongoing effectiveness of vaccines or previous infection in protecting against the new subvariants, antibodies from unvaccinated individuals who were infected with Omicron subvariants BA.1 or BA.2 in spring 2022 neutralised BA.2.12.1 with similar efficiency, but were much less potent against BA.4 and BA.5.

Antibodies induced by three doses of Pfizer/BioNTech’s vaccine blocked all Omicron subvariants, but inhibition was less efficient as compared to earlier SARS-CoV-2 variants, and inhibition of BA.2.12.1, BA.4, and BA.5 was less efficient compared to BA.1 and BA.2.

Similar results were obtained for antibodies induced by vaccination plus breakthrough infection. Although this so-called hybrid immunity conferred overall higher neutralising activity against all variants tested, inhibition of BA.2.12.1, BA.4 and BA.5 was significantly reduced.

“BA.2.12.1 and particularly BA.4 and BA.5 are antibody evasion variants. Vaccination will still protect against severe disease induced by these variants, but protection might be somewhat less efficient as that measured for previously circulating variants,” said Markus Hoffmann, senior author of the study.

Future studies will investigate whether BA.2.12.1, BA.4 and BA.5 are not only less efficiently inhibited by antibodies but also better at infecting lung cells. If this is the case, then an uptick in hospitalisations might be the consequence, although this has so far not been observed in South Africa, where BA.4 and BA.5 were first detected.

Drug regulators meet to discuss changes to COVID-19 vaccines, in face of Omicron BA.4 and BA.5

The European Medicines Agency and other regulators from around the world met to review the emerging evidence of reduction in the effectiveness of COVID-19 vaccines against the new Omicron BA.4 and BA.5 subvariants of SARS-CoV-2 and to discuss how vaccines could be adapted.

The meeting focused on identifying key principles to support changes to COVID-19 vaccines to better match Omicron variants of concern, and on ensuring global regulatory alignment.

The currently authorised COVID-19 vaccines continue to offer protection against severe disease, hospitalisation and death, but the regulators recognised that the continuous evolution of SARS-CoV-2 reduces the protection offered by the approved vaccines against infection and mild disease.

Although the Omicron BA.4 and BA.5 subvariants are dominant in many parts of the world, experience has shown that new variants may emerge rapidly and could replace those currently circulating very quickly, making it tricky to decide what targets updated vaccines should be aimed at.

Preliminary data indicate that adapted mRNA vaccines which incorporate an Omicron variant strain, can increase and extend protection, when used as a booster.

There is also emerging data showing a bivalent mRNA vaccine designed against both the original virus that emerged in Wuhan, China and against an Omicron strain, may provide some advantages in widening the immune response. EMA said such bivalent vaccines could be considered initially for use as boosters, but there is not enough data as yet to support their use for primary vaccination.

Vaccines which include other variants, for example the Beta variant, could also be considered for use as boosters if there is enough clinical trial data to demonstrate they neutralise Omicron and other variants of concern.

The regulators also highlighted the importance of planning effectiveness studies with adapted vaccines to determine the level of protection conferred from infection, hospitalisation and death in real-life conditions.

UK study probes the impact of recipient’s weight on effectiveness of COVID-19 vaccines

While obesity was flagged as a risk factor for more serious disease in the early stages of the COVID-19 pandemic, it was not known if two doses of vaccine are as effective against severe disease in people who are underweight, overweight or obese.

As a result of obesity being identified as a risk factor for severe COVID-19 early in the pandemic, the UK vaccine programme in 2021 gave priority to calling people with a body mass index of over 40 for vaccination.

But while the evidence was they were at risk of more severe disease, little was known about the effectiveness of COVID-19 vaccines for overweight and obese people.

Now a UK study involving more than nine million people has shown that while vaccinated people who are underweight or overweight are better protected than counterparts who have not been vaccinated, they are at greater risk of hospitalisation and death compared to vaccinated people of healthy weight.

Characteristics such as age, sex, smoking status, and social deprivation were accounted for in the analyses.

The study provides some of the first indicators as to the effectiveness of COVID-19 vaccines across body mass index (BMI) categories.

“Our findings provide further evidence that COVID-19 vaccines save lives for people of all sizes,” said lead author, Carmen Piernas of Oxford University’s department of primary care health sciences. The results provide reassurance to people living with obesity that vaccination substantially lowers their risk of severe illness if they are infected with COVID-19, she said.

Piernas and colleagues searched anonymised health records from more than 12 million patients across 1,738 GP practices in England. Of these, patients who were over 18 years old, had BMI data, and had not previously been infected with SARS-CoV-2 were included in the study.

Of over nine million people included in the study, 566,461 tested positive for SARS-CoV-2 during the study period, from 8 December 2020 - the date the first vaccine was given in the UK - to 17 November 2021. Of these, 32,808 were admitted to hospital and 14,389 died.

The proportion of people who had had no doses of any COVID-19 vaccine at the end of the study were 23.3% of the healthy weight group (817,741 of 3,509,231 people); 32.6% of the underweight group (104,488 of 320,737 people); 16.8% of the overweight group (513,570 of 3,062,925 people) and 14.2% of the obese group (322,890 of 2,278,649 people).

The risk of severe disease in vaccinated versus non-vaccinated people was compared at least 14 days after a second dose. The researchers found that being vaccinated offered high protection across all BMI groups, but that the effect was slightly lower in underweight people.

For all groups other than people who were underweight, being vaccinated meant they were around 70% less likely to be hospitalised than unvaccinated people. In addition, these groups were also around two-thirds less likely to die than their unvaccinated counterparts two weeks after a second dose.

Looking only at vaccinated people, even though vaccination helped reduce the number of severe COVID-19 cases, there was a significantly higher risk of severe disease for people who were underweight, overweight or obese, compared to people with a healthy BMI, following two doses of vaccine.

For example, a BMI of 17 was linked to a 50% increase in risk of hospitalisation compared with a healthy BMI of 23, and a very high BMI of 44 had three times the risk of hospitalisation compared with a healthy BMI. This is similar to the increased risk of severe COVID-19 outcomes shown prior to the vaccination programme.

“The cause of the increased risk among people with obesity is unknown,” Piernas said. “We suspect that these findings may be explained, in part, by an altered immune response in heavier weight individuals, but that is just speculation at this point. The reduced effectiveness of COVID-19 vaccines among people with a low BMI may also reflect a reduced immune response due to frailty or other conditions associated with low body weight.”

UK study probes the impact of recipient’s weight on effectiveness of COVID-19 vaccines

But while the evidence was they were at risk of more severe disease, little was known about the effectiveness of COVID-19 vaccines for overweight and obese people.

Characteristics such as age, sex, smoking status, and social deprivation were accounted for in the analyses.

The study provides some of the first indicators as to the effectiveness of COVID-19 vaccines across body mass index (BMI) categories.

“Our findings provide further evidence that COVID-19 vaccines save lives for people of all sizes,” said lead author, Carmen Piernas of Oxford University’s department of primary care health sciences. The results provide reassurance to people living with obesity that vaccination substantially lowers their risk of severe illness if they are infected with COVID-19, she said.

“The cause of the increased risk among people with obesity is unknown,” Piernas said. “We suspect that these findings may be explained, in part, by an altered immune response in heavier weight individuals, but that is just speculation at this point. The reduced effectiveness of COVID-19 vaccines among people with a low BMI may also reflect a reduced immune response due to frailty or other conditions associated with low body weight.”

It’s in the air: survival of SARS-CoV-2 in aerosol particles depends on humidity but not temperature

When SARS-CoV-2 is airborne after infected people cough or sneeze, the virus can lose up to 90% of its potency within 20 minutes, according to the first study to investigate the decrease in infectivity of the virus in aerosol particles over periods from seconds to a few minutes.

Scientists from Bristol University looked see how the survival and infectivity of airborne SARS-CoV-2 inhalable particles is affected by environmental conditions such as relative humidity and temperature. Relative humidity measures how much moisture there is in the air compared to how much there could be at that temperature. Ideal indoor levels are between 40% to 60%.

The researchers generated airborne particles and examined how temperature and humidity drive changes in infectivity at timescales from five seconds to 20 minutes. The same experiment was carried out comparing four different SARS-CoV-2 variants.

There was a significant fall in infectivity within the first ten minutes of aerosol particle generation that was strongly dependent on the environmental relative humidity, but not temperature, across the different SARS-CoV-2 variants.

A 50% decrease in airborne infectivity occurred at low relative humidity (of less than 50%) within ten seconds of aerosol generation. This happens because the airborne particles dry out and rapidly lose moisture, forming solid particles.

At high relative humidity, the loss in infectivity following aerosolisation was more gradual, with a steady loss of infectivity of 50% within the first five minutes and 90% within twenty minutes.

Jonathan Reid, professor of physical chemistry said, “We know that aerosol particles, exhaled when infected individuals breathe, speak or cough, can transmit viruses. Understanding the mechanisms that influence the survival of pathogens while airborne is a further piece of the jigsaw puzzle in understanding the spread of diseases such as COVID-19.”

Infection with SARS-CoV-2 impairs insulin signalling

While COVID-19 is categorised as a respiratory disease, it has harmful effects far beyond the lungs. Now, Japanese researchers have identified a gene that mediates the effects of SARS-CoV-2 infection on blood sugar metabolism and shown the virus can cause metabolic problems, including diabetes, by interfering with insulin signalling.

The researchers hypothesised that SARS-CoV-2 was impacting insulin signalling and causing problems with blood sugar regulation. To test this, they analysed datasets of gene expression from patients, as well as in vivo and in vitro models, looking for genes that were noticeably over- or under-expressed.

“The results were striking,” said Iichiro Shimomura, senior author of the study. Infection with SARS-CoV-2 affected the expression of insulin signalling pathway components in the lung, liver, adipose tissue, and pancreatic cells. These changes were attributed in part to activation of the interferon regulatory factor 1 gene (IRF1).

Further investigation showed that IRF1 expression is elevated in older patients, men, obese individuals, and patients with diabetes. The combined effects of older age, male sex, obesity and diabetes with SARS-CoV-2 means that the expression of IRF1 occurs at an increased rate, which may explain why these patients are more vulnerable to COVID-19.

In addition, patients who were critically ill with COVID-19 had higher IRF1 expression and lower insulin signalling pathway genes in their blood, compared to noncritical patients.

Given the devastating impact that COVID-19 can have on multiple organ systems, treatment strategies that could decrease the effect of the disease on blood sugar metabolism could be vitally important. By identifying patients at greater risk of experiencing these effects and intervening to decrease IRF1 activation, some of the severe consequences of COVID-19 could be avoided in susceptible populations, the researchers say.

Still no evidence ivermectin effective treatment for COVID-19

There is no evidence to support the use of ivermectin for treating or preventing COVID-19 infection, according to a meta-analysis of 11 trials involving 3,409 people.

The drug, which is used to treat parasites such as scabies in humans, was screened in 2020 for activity against COVID-19. Laboratory tests suggested a weak effect on SARS-CoV-2 virus in a test-tube, but the dose required for humans would need to be so large it was dismissed as an option.

However, a number of small trials suddenly appeared in the literature, suggesting large effects on mortality. This caused an explosion of interest, with some groups lobbying for it to be used worldwide. Shortly after, several of these studies were shown to be fabricated; others had serious data errors and were poorly conducted.

In the light of these fake and poorly conducted studies, the new review reappraised eligible studies specifically in relation to research integrity. The authors only included randomised controlled trials that were registered in advance in registries meeting the WHO guidelines for clinical trial registration.

The researchers also investigated whether the studies had adequate ethics approval and if the results were plausible.

Overall, the review found no evidence to support the use of ivermectin for treating or preventing COVID-19 infection.

Discovery of new COVID-19 infection mechanism offers clue to SARS-CoV-2 leap to humans

New research has shown the original SARS-CoV-2 viral strain was able to latch on to sugars called sialic acids found on the surface of human cells, a function that later strains did not retain.

This function in the early strain raises the possibility that this is how the virus first transferred from animals to humans. Subsequent variants do not have the ability to latch onto sialic acid and instead rely on receptors on their spikes proteins to attach to ACE2 receptors on human cells.

“Two of the ongoing mysteries of the coronavirus pandemic are the mechanisms behind viral transmission and the origins of the zoonotic leap,” said researcher Ben Davis of the Rosalind Franklin Institute at Oxford University. “There is evidence that some influenza viruses can grab sialic acid on the surface of human host cells, and this has been seen in Middle Eastern Respiratory Syndrome (MERS), which is a coronavirus. Although SARS-CoV-2 variants of concern had not shown this mechanism, our research finds that the viral strain that emerged in early 2020 could use this as a way of getting into human cells.”

The binding mechanism is found on the end of the N-terminal domain, a part of the virus that evolves rapidly. The domain has previously been implicated in sialic acid binding but until the researchers at the Rosalind Franklin Institute applied high-resolution precision imaging and analysis this was unproven.

As to why the virus has discarded the sugar binding feature as it has evolved into new variants, Davis suggests it may be necessary for the initial zoonotic leap into humans from animals but can then be hidden until it is required again, particularly if the function is broadly detrimental to the virus’s mission of replication and infection within humans.

The finding correlates with evidence from the first wave in Italy. The Italian Genomics Consortium saw a correlation between severity of COVID-19 illness and genetics, as patients with a particular gene mutation that affects the type of sialic acid on cells were underrepresented in intensive care units. This suggested the virus was finding it easier to infect some genotypes compared to others.

“With our ultra-high precision imaging and new method of analysis we can see a previously unknown structure at the very end of the SARS-CoV-2 spike,” said James Naismith, director of the Rosalind Franklin Institute. “The amazing thing is that our finding correlates with what the Italian researchers noted in the first wave, suggesting that this was a key role in early infection.

COVID-19 vaccines estimated to have prevented 19.8M deaths in first year after introduction

A new mathematical modelling study has estimated COVID-19 vaccines reduced the potential global death toll during the pandemic by more than half in the year following their implementation, with 19.8 million out of a potential 31.4 million deaths prevented worldwide, according to estimates based on excess deaths from 185 countries.

The study estimates a further 599,300 lives could have been saved if the World Health Organisation’s target of vaccinating 40% of the population in each country with two or more doses by the end of 2021 had been met.

“Our findings offer the most complete assessment to date of the remarkable global impact that vaccination has had on the COVID-19 pandemic,” said Oliver Watson, lead author of the study, from Imperial College London.

Of the deaths estimated to have been prevented in the first year after vaccines were introduced, almost 7.5 million deaths were prevented in countries covered by the COVID-19 Vaccine Access initiative (COVAX), set up because it was clear early on that global vaccine equity would be the only way out of the pandemic.

“Our findings show that millions of lives have likely been saved by making vaccines available to people everywhere, regardless of their wealth,” said Watson. “However, more could have been done. If the targets set out by the WHO had been achieved, we estimate that roughly 1 in 5 of the estimated lives lost due to COVID-19 in low-income countries could have been prevented.”

Since the first COVID-19 vaccine was administered outside of a clinical trial setting on 8 December 2020, almost two thirds of the world’s population has received at least one dose of a COVID-19 vaccine. Despite the speed of the vaccine roll-out worldwide, more than 3.5 million COVID-19 deaths have been reported since the first vaccine was administered in December 2020.

“Quantifying the impact that vaccination has made globally is challenging because access to vaccines varies between countries, as does our understanding of which COVID-19 variants have been circulating, with very limited genetic sequence data available for many countries,” said Gregory Barnsley, co-first author of the study. “It is also not possible to directly measure how many deaths would have occurred without vaccinations. Mathematical modelling offers a useful tool for assessing alternative scenarios, which we can’t directly observe in real life.”

More than three quarters, or 15.5 million of deaths averted were due to the direct protection against severe symptoms provided by vaccination, leading to lower mortality rates. The remaining 4.3 million averted deaths were estimated to have been prevented by indirect protection from reduced transmission of the virus in the population and reduced burden on healthcare systems, thereby improving access to medical care for those most in need.

Vaccine impact changed over time and in different areas of the world as the pandemic progressed, the study found. In the first half of 2021, the greatest number of deaths averted by vaccination was seen in lower middle-income countries, resulting from the significant epidemic wave in India as the Delta variant emerged. This subsequently shifted to the greatest impact being concentrated in higher income countries in the second half of 2021, as restrictions on travel and social mixing were eased in some areas, leading to greater virus transmission.

Overall, the number of estimated deaths prevented per person was greatest in high income countries, reflecting the earlier and wider roll out of vaccination campaigns in these areas, with 66 deaths prevented per 10,000 people in high-income countries vs 2.711 deaths prevented per 10,000 people in low-income countries.

For the 83 countries included in the analysis that are covered by the COVAX commitment to affordable vaccines, an estimated 7.4 million deaths were averted out of a potential 17.9 million.

Pause in immune-supressing drugs boosts effectiveness of COVID-19 vaccination

A UK clinical trial has found that interrupting the treatment of people on long-term immune supressing drugs for two weeks after a COVID-19 booster vaccination, doubles their antibody response to the vaccine.

The trial has implications for people on immune-supressing drugs, who are among the millions of clinically vulnerable patients advised to shield during the pandemic.

The study was planned to recruit 560 patients but recruitment was stopped early when interim results from the first 254 participants showed a clear result.

Methotrexate is the most commonly used immune-suppressing drug, with around 1.3 million people in the UK prescribed it for inflammatory diseases such as rheumatoid arthritis, and skin conditions such as psoriasis. Many of them were advised to shield during the first phase of the COVID-19 pandemic, because while methotrexate is effective at controlling these conditions it reduces the body’s ability to fight infections and the ability to generate a robust response to vaccines, including those against COVID-19.

The trial evaluated temporarily stopping, versus continuing methotrexate treatment immediately after a third booster dose of COVID-19 vaccine.

After 4 weeks and 12 weeks, levels of antibodies against the viral spike protein were more than two-fold higher in the group where methotrexate was suspended for two-weeks following vaccination, compared to the group who continued use.

There was a short-term increase in risk of flare-up of inflammatory conditions. However, most could be self-managed and there was no adverse impact on quality of life.

EMA approves Valneva’s whole inactivated virus COVID-19 vaccine

The European Medicines Agency (EMA) is recommending approval of French biotech Valneva’s inactivated whole-virus COVID-19 vaccine for use in primary vaccination in people from 18 to 50 years of age.

Although late to the party, there is hope that the more traditional format of the vaccine will persuade people who did not want to be vaccinated with the earlier novel vaccines using mRNA and viral vectors as delivery vehicles, to overcome their reservations.

Thomas Lingelbach, CEO of Valneva said, “We hope that the European Commission and its member states will recognise the potential advantages of an inactivated vaccine and make a meaningful order, since we have clear evidence that Europeans are seeking a more traditional vaccine technology. Our aim is to further support public health in Europe by providing a new option for the 15% of Europeans over 18 who are not yet vaccinated.”

On May 16 the Commission cancelled its advance purchase agreement with Valneva, citing its right to do so if the vaccine was not approved by 30 April 2022. At that point Lingelbach said, “The European Commission decision is regrettable especially as we continue to receive messages from Europeans who are looking for a more traditional vaccine solution. We have started a dialogue with member states who are interested in our inactivated approach.”

The EMA nod follows conditional marketing authorisation in the UK which was granted in April 2022, emergency use authorisation granted in the United Arab Emirates in May 2022 and in Bahrain in March.

The vaccine, VLA2001, consists of inactivated whole virus particles of SARS-CoV-2 with high S-protein density, in combination with two adjuvants, alum and CpG 1018. The adjuvant combination has consistently induced higher antibody levels in preclinical experiments than alum-only formulations. VLA2001’s manufacturing process includes chemical inactivation to preserve the native structure of the S-protein.

Long COVID a problem for children too

The largest study to date of Long COVID symptoms in children aged 0-14 years confirms that children who have received a COVID-19 diagnosis can experience symptoms lasting at least two months.

The study used national level sampling of children in Denmark and matched COVID-19 positive cases, with a control group of children with no prior history of a COVID-19 infection.

“The overall aim of our study was to determine the prevalence of long-lasting symptoms in children and infants, alongside quality of life, and absence from school or day care,” said Selina Kikkenborg Berg of Copenhagen University Hospital. While children with a positive COVID-19 diagnosis are more likely to experience long-lasting effects, the pandemic has affected every aspect of all young people’s lives. Further research into the long-term consequences of the pandemic on all children will be important going forwards,” Berg said.

Most previous studies of Long COVID in young people have focussed on adolescents, with infants and toddlers seldom represented.

The most commonly reported symptoms among children 0-3 years old were mood swings, rashes, and stomach aches. Among 4-11 years old the most commonly reported symptoms were mood swings, trouble remembering or concentrating, and rashes, and among 12-14 years old, fatigue, mood swings, and trouble remembering or concentrating.

Children diagnosed with COVID-19 in all age groups were more likely to experience at least one symptom for two months or longer than the control group.

The types of non-specific symptoms associated with long COVID are often experienced by otherwise healthy children; headache, mood swings, abdominal pain, and fatigue are all symptoms of common ailments. However, this study revealed that children with a positive COVID-19 diagnosis were more likely to experience long-lasting symptoms than children who had never had a positive diagnosis.

“The opportunity to undertake such research is rapidly closing as the vast majority of children have now had a COVID-19 infection, for example 58% of children in Denmark had lab confirmed infection between December 2021 and February 2022,” said Berg. Knowledge of long-term symptom burden in SARS-CoV-2 positive children is essential to guide diagnosis and care.

Trainspotting: risk of SARS-CoV-2 transmission same wherever you sit

Researchers have demonstrated how airborne diseases such as COVID-19 spread along the length of a train carriage and shown there is no ‘safest spot’ for passengers to minimise the risk of transmission.

The researchers from Cambridge University and Imperial College London developed a mathematical model to help predict the risk of disease transmission in a train carriage and found that in the absence of ventilation systems that draw in fresh air, the risk is the same along the entire length of the carriage.

The model, which was validated with a controlled experiment in a real train carriage, also showed masks are more effective than social distancing at reducing transmission, especially in trains that are not ventilated with fresh air.

The researchers say the results highlight how important it to improve train ventilation systems.

“In order to improve ventilation systems, it’s important to understand how airborne diseases spread in certain scenarios, but most models are very basic and can’t make good predictions,” said researcher Rick de Kreij. “Most simple models assume the air is fully mixed, but that’s not how it works in real life.”

Many different factors can affect the risk of transmission in a train, including whether the people in the train are vaccinated, whether they’re wearing masks, how crowded it is. “Any of these factors can change the risk level, which is why we look at relative risk, not absolute risk. It’s a toolbox that we hope will give people an idea of the types of risk for an airborne disease on public transport,” de Kreij said.

Newer variants of Omicron escape antibodies elicited by infection with earlier Omicron variant

The SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 that are currently causing most COVID-19 infections, exhibit higher transmissibility than their predecessor, BA.2.

In investigating the reason for this, scientists in China made structural comparisons of the Spike protein by which the virus locks onto the human ACE2 receptor and enters the host cell. They showed that BA.2.12.1 and BA.4/BA.5 have comparable ACE2-binding affinities to BA.2.

However, it was also shown that BA.2.12.1 and BA.4/BA.5 are more able to evade neutralising antibodies in blood samples from people who had received three doses of COVID-19 vaccine, and more significantly, in the blood of people who had been infected with the earlier BA.1 Omicron variant after receiving three doses of vaccine.

In the paper published in Nature, the researchers say their results indicate that Omicron may have evolved mutations to evade the immunity elicited by BA.1 infection. That suggests vaccine boosters designed against BA.1 may not achieve broad-spectrum protection against newer Omicron variants, they say.

Omicron variant less likely to cause Long COVID than the Delta variant

An analysis by researchers at King’s College London of data from ZOE, a smartphone app that has been gathering information on COVID symptoms from the general public since the start of the pandemic, has found Long COVID is less likely after infection with the Omicron variant than the Delta variant.

Long COVID is defined in UK guidelines as having new or ongoing symptoms four weeks or more after the start of disease. Symptoms include fatigue, shortness of breath, loss of concentration and joint pain. These can adversely affect day-to-day activities, and in some cases can be severely debilitating.

The odds of experiencing Long COVID were between 20-50% less with Omicron than Delta, depending on age and time since vaccination.

The study identified 56,003 UK adult cases first testing positive between 20 December 2021 and 9 March 2022, when Omicron was the dominant strain. Researchers compared these cases to 41,361 cases first testing positive between 1 June 2021 and 27 November 2021 when the Delta variant was dominant.

The analysis shows 4.4% of Omicron cases were Long COVID, compared to 10.8% of Delta cases.

However, the absolute number of people experiencing Long COVID was in fact higher in the Omicron period, because of the vast numbers of people infected with Omicron from December 2021 to February 2022.

The UK Office of National Statistics estimated the number of people with Long COVID increased from 1.3 million in January 2022 to 2 million as of 1 May 2022.

Drug regulators reflect on the value of sharing real world evidence and the lessons of the pandemic

International regulators have issued a report outlining what they have learned from the high level of international collaboration in pooling and analysing data that was spurred by the pandemic, and which allowed them to rapidly generate real world evidence of the safety and effectiveness of the vaccines and antivirals approved to prevent and treat COVID-19.

In particular, the report, issued under the auspices of the International Coalition of Medicines Regulatory Authorities, focusses on the importance of sharing data for vaccines surveillance; research on the safety of drugs and vaccines in pregnancy; and the building of international cohorts of patients to increase the statistical power of observational studies.

The contributors to the report represent more than 28 drugs regulatory authorities as well as experts from the World Health Organisation.

The report acknowledges the importance of sharing of data, experience and tools, and says there is broad agreement that rapid generation of evidence as a result of active interactions between regulators, researchers and academia is crucial for regulatory decision-making in case of a new pandemic or other public health crises.

In the case of COVID-19 and its effects on pregnant women and their babies, data was gathered from around the world, the first time where such an exhaustive collaborative collection of data on this special population had been achieved. It was shown that performing studies based on the same protocol with some adaptations to the local databases made it possible to conduct extremely strong studies in relatively short time periods.

The report also identifies opportunities for strengthening international collaboration beyond the pandemic, and highlighted that a state of readiness is essential.

New research identifies more than 1,000 genes linked to severe COVID-19

An US/UK research collaboration has identified genetic factors that lead some healthy adults with the COVID-19 infection become seriously ill, whilst others have few symptoms.

While it is known that age, body mass index and pre-existing health problems account for some of the disparities in severity of infection, genetics also plays a significant role.

Using machine learning, the researchers identified more than 1,000 genes linked to the development of severe COVID-19 and which particularly affect the function of white blood cells called natural killer cells.

This is said to be one of the first studies to link coronavirus-associated genes to specific biological functions.

“During the research we discovered the genetic architecture underlying coronavirus infection, and found that these 1,000 genes account for three quarters of the genetic drivers for severe COVID-19,” said Johnathan Cooper-Knock, lecturer in the Department of Neuroscience at Sheffield University. “This is significant in understanding why some people have had more severe symptoms of Covid-19 than others.”

The researchers used several large data sets to unpack the genetics behind severe COVID-19. The first, containing sequence data from healthy human lung tissue was used to track gene expression in 19 different types of lung cells, including epithelial cells that line the respiratory tract and which are the first defence against infection.

That was cross referenced against the COVID-19 Host Genetics Initiative, one of the largest genetic studies of critically ill coronavirus patients, to look for mutations that might indicate someone is at a higher risk for severe COVID-19.

By layering the mutations onto the cell-specific genomes of healthy cells the researchers pinpointed which genes were dysfunctioning and within which cell-types. They found that severe COVID-19 is largely associated with a weakened response from two immune cells, natural killer cells and T cells.

Cooper-Knock said, “We found that in people with severe coronavirus infection, critical genes in NK cells are expressed less, so there’s a less robust immune response. The cell isn’t doing what it’s supposed to do.”

The findings lay the foundation for a genetic test to predict who is at an increased risk for severe COVID-19.

Trials of NK cell infusions for severe COVID-19 are now underway.

EMA reviewing new version of Pfizer/BioNTech COVID-19 vaccine

The European Medicines Agency has started a rolling review for a version of the Pfizer/BioNTech COVID-19 vaccine that has been designed to provide better protection against variants of SARS-CoV-2.

The review will initially focus on manufacturing of the vaccine, and as there is progress in the development of the adapted vaccine, EMA will look at data on the immune response to the vaccine and its efficacy against Omicron variants.

Details about the adapted vaccine, for example whether it will specifically target one or more SARS-CoV-2 variants or subvariants, are not yet defined.

French scientists identify 2 antibodies that are effective against all SARS-CoV-2 variants

French researchers have found two broadly neutralising antibodies that have the potential to provide long-acting immunity against COVID-19 in immunocompromised people.

The antibodies were effective against all SARS-CoV-2 variants of concern tested and could be used alone or in an antibody cocktail to diminish the risk of infection.

The researchers at the Institut Pasteur, Université Paris Cité, and INSERM examined 102 SARS-CoV-2 spike monoclonal antibodies cloned from blood cells of patients who recovered from COVID-19. They found two antibodies, labelled Cv2.1169 and Cv2.3194, that were the only ones to neutralise all SARS-CoV-2 variants, including Omicron BA.1 and BA.2 subtypes.

The two antibodies also were fully active against Alpha, Beta, Gamma, and Delta variants. A modified version of the Cv2.1169 antibody was also effective at treating SARS-CoV-2 infection in mice and hamsters.

“The broadly neutralising antibodies we described were more efficient in vitro than many anti–SARS-CoV-2 monoclonals previously approved by the FDA for treatment or prevention,” said Hugo Mouquet, head of the Laboratory of Humoral Immunology at the Institut Pasteur, who led the study. “Therefore, we are pretty confident that they represent premium candidates for pre-exposure prophylaxis in immunocompromised patients.”

Previous research has shown that SARS-CoV-2 spike-specific monoclonal antibodies play a key role in providing in vivo protection, however, immunocompromised people still lack effective immunity against SARS-CoV-2 infection.

The first molecule being developed based on the new research, SPK001 is expected to start clinical trials shortly.

The research has its roots in a task force launched by the Institut Pasteur in the early days of the COVID-19 pandemic.

Notably, one of the two broadly neutralizing antibodies, Cv2.1169, is an immunoglobulin A that is produced by B cells in the respiratory tract, and can be crucial in the early response to respiratory pathogens like SARS-CoV-2.

COVID-19 pandemic in Finland seeded from Italy, Austria and Spain

Researchers from the University of Helsinki and KU Leuven who investigated the arrival and spread of SARS-CoV-2 in Finland in 2020 found a total of 42 independent virus lineages reached the country in spring 2020. Most of these came from Italy, Austria and Spain, but only a handful caused large chains of transmission.

“Four of these lineages caused two-thirds of the entire epidemic in Finland in spring 2020, while a single virus lineage from Spain led to a major transmission chain that covered one-third of the epidemic in the country,” said Ravi Kant of the Department of Virology at Helsinki University.

In the early stages of the pandemic, one of the biggest problems in monitoring the chains of transmission was the genetic similarity of the virus everywhere in the world – there were very few differences in the viral genome between individual countries and chains of transmission.

Philippe Lemey, a specialist in evolutionary and computational virology at KU Leuven, developed an analysis technique that combines data on human mobility at individual and population levels with the sequence analysis of the viral genome, and this was used to analyse SARS-CoV-2 sequencing data from Finland.

This showed that Austria, Spain and Italy, the countries in Europe that had the earliest infection spikes, starting in February 2020, were the most significant sources of coronavirus spreading to Finland.

“Our results show that only a small share of infections is transmitted further, indicating that if travel restrictions and quarantines, testing, tracing and isolation schemes, or other border control measures are deployed early enough, they can delay the development of cases of infection into widespread transmission chains in society. However, these measures will only be effective if combined with other preventive measures, and if the viral strains to be prevented have not already spread,” said Olli Vapalahti, professor in the Department of Virology at Helsinki University.

Questions remain about the ongoing evolution of the virus. Originally, SARS-CoV-2 spread to humans as a zoonotic disease, most likely from bats.

“The circulation of the virus in a new host species requires numerous changes: for instance, the virus must adjust its surface proteins to make them attach more effectively to the cells of the host. In addition, the virus must overcome the host’s innate defences,” said Tarja Sironen, associate professor at Helsinki University. “In fact, the rapid transmission of coronavirus between people in large human populations has produced complex genetic diversity in the virus. At the moment, one of the most central questions in related research is how these different changes alter the biological characteristics of the virus, and what kind of changes in selection pressure is guiding the virus towards in the future.”

The first SARS-CoV-2 case was diagnosed in Finland on 29 January 2020 in a tourist who arrived from Wuhan, China. However, at this point the infection was not transmitted to others in Finland, and the first wave of the epidemic in Finland did not begin until the end of February 2020, peaking in early May and ending by early June.

Canadian scientists prove that inhaled COVID-19 vaccines are better than nasal sprays

A comparison of respiratory vaccine delivery systems carried out by scientists at McMaster University, Canada has confirmed that inhaled aerosol vaccines provide far better protection and stronger immunity than nasal sprays.

While nasal sprays reach primarily the nose and throat, inhaled aerosols bypass the nasal passage and deliver vaccine droplets deep in the airway, where they can induce a broad protective immune response, the researchers say.

Infections in the upper respiratory tract tend to be non-severe. In the context of infections caused by viruses like influenza or SARS-CoV-2, it tends to be when the virus gets deep into the lung that it causes severe illness, said Matthew Miller, a co-author of the study, who is a specialist in viral pandemics.

“The immune response you generate when you deliver the vaccine deep into the lung is much stronger than when you only deposit that material in the nose and throat because of the anatomy and nature of the tissue and the immune cells that are available to respond are very different,” Miller said.

The study for the first time provides strong preclinical evidence to support the development of inhaled aerosol delivery over nasal spray for human vaccination against respiratory infections including COVID-19, the researchers say.

More than 6.3 million have people died during the COVID-19 pandemic, and respiratory infections remain a significant cause of illness and death throughout the world, driving an urgent and renewed worldwide effort to develop vaccines that can be delivered directly to the mucous lining of the respiratory tract.

Scientists at McMaster, who have developed an inhaled form of a COVID-19 vaccine, believe this deep-delivery method offers the best defence against the current and future pandemics.

A phase I clinical trial is currently under way to evaluate the inhaled aerosol vaccine in healthy adults who had previously received two or three doses of an injected COVID mRNA vaccine.

Previous research by the McMaster team has shown that in addition to being needle-free and painless, an inhaled vaccine is so efficient at targeting the lungs and upper airways that it can achieve maximum protection with a much smaller dose than injected vaccines.

Sanofi-GSK next-generation COVID-19 vaccine is effective against variants of concern, including Omicron

Two clinical trials of Sanofi’s next-generation COVID-19 booster vaccine have shown it increases neutralising antibodies above baseline against multiple variants of concern in adults who have already been vaccinated with mRNA COVID-19 vaccines.

In particular, the vaccine generated a 40-fold increase in neutralising antibodies against Omicron BA.1 and BA.2.

The second study demonstrated that following primary vaccination with two doses of Pfizer-BioNTech’s vaccine, the Sanofi-GlaxoSmithKline next-generation booster candidate generated a higher immune response than Pfizer-BioNTech’s booster or the Sanofi-GSK first-generation booster. The proportion of participants with at least a 10-fold increase in neutralising antibody levels between day 0 and day 15 was 76.1% for the Sanofi-GSK next-generation booster, versus 63.2% for the Pfizer BioNTech booster, and 55.3% for the Sanofi-GSK first-generation parent booster candidate

“COVID-19 keeps evolving and the combination of emergence of variants and waning immunity is likely to lead to the need for additional booster shots, at least in some populations,” said Thomas Triomphe, executive vice president of Sanofi Vaccines. “Seeing the cross-neutralisation data from the [second] study, we believe this next-generation booster could have an important role to play for public health vaccination campaigns. We look forward to submitting these data to global regulatory authorities.”

Sanofi said the data supporting its next-generation booster vaccine will be submitted to regulators in the upcoming weeks, with the aim of making it available later this year.

Moderna’s COVID-19 booster vaccine shown to provide protection against Omicron variant

Moderna has announced new clinical data on its COVID-19 booster vaccine candidate, mRNA-1273.214, which is designed to be effective against the Omicron variant, showing a single dose met all pre-specified endpoints.

That included superior neutralising antibody response against Omicron, currently the cause of most infections, one month after administration, when compared to the original mRNA-1273 vaccine, which was designed to protect against the original variant from Wuhan, China.

The booster dose of mRNA-1273.214 was generally well-tolerated, with side effects comparable to a booster dose of mRNA-1273.

"The preliminary data analysis on mRNA-1273.214 […] is the second demonstration of superiority of our bivalent booster platform against variants of concern,” said Stéphane Bancel, CEO of Moderna. "We anticipate more durable protection against variants of concern with mRNA-1273.214, making it our lead candidate for a fall 2022 booster. We are submitting our preliminary data and analysis to regulators with the hope that the Omicron-containing bivalent booster will be available in the late summer.”

Neutralising antibody levels with mRNA-1273.214 were also significantly higher against all other variants of concern - Alpha, Beta, Gamma and Delta.

EMA names drugs on COVID-19 critical list

The European Medicines Agency’s medicines shortages steering group has adopted the list of critical drugs for the COVID-19 public health emergency, meaning their supply and demand will be closely monitored to identify and manage potential or actual shortages.

Given the current stage of the pandemic, the published list contains all the EU-approved vaccines and therapeutics.

Companies marketing the products on the list, which was approved on 7 June, are required to regularly update EMA about potential or actual shortages and available stocks, forecasts of supply and demand.

To ensure stocks are sufficient, member states will be providing regular reports on estimated demand at a national level, enabling EMA to recommend and coordinate appropriate EU-level actions to the European Commission and EU member states.

The medicines shortages group was set up in response to EMA being given greater responsibility for crisis preparedness for public health emergencies, and to coordinate urgent action on the supply of drugs within the EU.

€9.18M Horizon Europe project to develop early warning system of emerging pathogens

IDAlert, a Horizon Europe project kicking off at the start of June, aims to tackle the emergence and transmission of pathogens from animals to humans, developing novel indicators, early warning systems and tools for decision-makers, and by investigating adaptation and mitigation strategies make Europe more resilient to emerging health threats.

As the planet heats up due to climate change, outbreaks of zoonotic diseases that spread from animals to humans are on the rise. Warmer temperatures, more variable rainfall, and the loss of biodiversity, influence the survival and spread of zoonotic pathogens, and the reproduction and geographic location of their vectors, such as mosquitoes or ticks.

Past and recent health crises, including the COVID-19 pandemic, have shown there is a need for stronger and more inclusive preparedness and responsiveness to epidemic-prone pathogens at the EU and global level. To address this, IDAlert will develop a range of decision support tools and systems to enable decision makers to react sooner.

Amongst these will be climate and health indicators for viruses circulating among wild birds and mosquitoes, and monitoring mechanisms to improve surveillance, early warning, and response systems.

IDAlert will also assess the costs, effectiveness, benefits and viability of adaptation measures and strategies to improve the climate resilience of health systems in Europe.

Finally, the project will look at socioeconomic aspects, investigating the emergence, transmission, and spread of zoonotic pathogens and how policy can help reduce their impacts.

The tools and methods developed in the project will be validated in key hotspot sites in Spain, the Netherlands, Greece, Sweden, and Bangladesh, all of which are experiencing rapid urban transformation and climate-induced disease threats.

IDAlert - Infectious Disease decision support tools and Alert systems to build climate Resilience to emerging health Threats - is a five year project involving 19 organisations from Sweden, Germany, France, Spain, Greece, The Netherlands, Italy, UK, and Bangladesh.

Babies born to mothers who had COVID-19 during pregnancy seem to show neurodevelopmental differences

Spanish researchers have found that babies born to mothers who were infected with COVID-19 while pregnant show greater difficulties in relaxing and adapting their bodies when they are being held, compared to infants from non-infected mothers. This is especially the case when infection happened late in pregnancy.

In addition, infants whose mothers had COVID-19 tend to show greater difficulty in controlling head and shoulder movements, suggesting a possible COVID-19 effect on motor function.

The data were presented at the European Congress of Psychiatry held from 4 – 7 June in Budapest.

The results come from an initial evaluation of the Spanish COGESTCOV-19 project, which followed the course of pregnancy and baby development in mothers infected with COVID-19. The data relate to pregnancy and post-natal assessment at 6 weeks after birth, but the project will continue to see if there are longer-term effects. The group will monitor infant language and motor development between 18 and 42 months old.

The initial evaluation compared babies born to 21 COVID positive pregnant women and their babies, with 21 healthy controls at the Marqués de Valdecilla University Hospital in Santander, Spain. The mothers underwent a series of tests during and after pregnancy.

The post-natal tests included the Neonatal Behavioural Assessment Scale, which measures a baby’s movement and behaviour.

One of the researchers, Águeda Castro Quintas from the University of Barcelona Network Centre for Biomedical Research in Mental Health) said, “We found that certain elements of the NBAS measurement were changed in 6-week-old infants who had been exposed to the SARS-COV-2 virus. Effectively they react slightly differently to being held or cuddled.”

The researchers note that these are preliminary result, but this is part of a project following a larger sample of 100 mothers and their babies. They have also been monitored during pregnancy, and after birth. It is also planned to compare these mothers and babies with data from another similar project, which is looking at the effect of stress and genetics on a child’s neurodevelopment.

Project leader Rosa Ayesa Arriola said, “This is the right moment to establish international collaborations that would permit us to assess long-term neurodevelopment in children born during the COVID-19 pandemic. Research in this field is vital in understanding and preventing possible neurological problems and mental health vulnerabilities in those children in the coming years.”

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

Long-term exposure to air pollution is linked to a greater risk of severe COVID-19, according to new research presented at the annual meeting of the European Society of Anaesthesiology and Intensive Care in Milan, Italy, 4-6 June.

The study by German researchers found that people living in counties with higher levels of the pollutant nitrogen dioxide (NO2) were more likely to need to be admitted to intensive care and mechanical ventilation if they had COVID-19.

Long-term exposure to NO2 that is released into the atmosphere when fossil fuels are burned, can have harmful effects on the lungs. This includes damage to the endothelial cells, which play a key role in oxygen transfer from inhaled air to the blood.

Although the links between air pollution and COVID-19 have previously been demonstrated by researchers in Spain, Mexico, Canada and other countries, few of these studies have focused on severity of disease or taken into account population density, underlying health conditions and other factors which affect the impact of the disease.

Susanne Koch, of the Department of Anaesthesiology & Intensive Care, Charité – Universitätsmedizin Berlin and colleagues explored the impact of long-term air pollution on the need for ICU treatment and mechanical ventilation of COVID-19 patients.

Air pollution data from 2010 to 2019 was used to calculate the long-term annual mean level of NO2 for each county in Germany. The highest level was in Frankfurt and the lowest level in Suhl, a small county in Thuringia.

The German Interdisciplinary Association for Intensive Care and Emergency Medicine registry, set up to monitor ICU capacity during the pandemic, was used to provide information on how many COVID-19 patients in each hospital needed ICU treatment and mechanical ventilation.

The study found that there was a greater need for ICU treatment and mechanical ventilation of COVID-19 patients in counties with higher long-term annual mean NO2 levels.

On average, 28 ICU beds and 19 ventilators were needed for COVID-19 patients in each of the ten counties with the lowest long-term NO2 exposure, during the month studied. This compares to an average of 144 ICU beds and 102 ventilators in the ten counties with the highest long-term NO2 exposure.

While the results do not prove causation, there is a potential biological explanation for them.

ACE-2, the protein that the COVID-19 virus binds to when entering our cells, has many key roles in the body, including helping down-regulate the activities of angiotensin II, a protein which increases inflammation.

When the SARS-CoV-2 virus binds to ACE-2, however, these brakes are removed. Air pollution also releases the brakes and so the combination of COVID-19 and long-term air pollution exposure could lead to more severe inflammation and more severe COVID-19.

“Long-term exposure to NO2 long before the pandemic may have made people more vulnerable to more severe COVID-19 disease,” Koch said. “Exposure to ambient air pollution can contribute a range of other conditions, including heart attacks, strokes, asthma and lung cancer and will continue to harm health long after the COVID-19 pandemic ends.”

Swedish researchers find new coronavirus in voles

Researchers from the Zoonosis Science Centre at Uppsala University have identified a new coronavirus in a study of approximately 260 bank voles caught around Grimsö in Örebro County. The data show the virus is well established in Sweden’s red-backed voles.

“Between 2015 and 2017, we consistently found what we have called the ‘Grimsö Virus’ in 3.4% of these voles, which would suggest that the virus is widespread and common in Sweden’s bank voles,” said Åke Lundkvist, professor in virology and head of the Zoonosis Science Centre.

Researchers at the centre map zoonotic viruses to increase the understanding of the interaction between viruses and host animals. Unlike the SARS-CoV and MERS coronaviruses that originate in bats, some seasonal coronaviruses appear to have spread to humans from rodents like rats, mice and voles.

In recent years, there has been a dramatic increase in the number of infectious diseases that can be linked to small mammals like rodents, and research around the ecology of these host animals is an essential component in the work to prevent future outbreaks.

The bank vole (Myodes glareolus) is one of Europe’s most common rodents. Previous studies have found several coronaviruses circulating amongst these animals in countries including the UK, Poland, France and Germany.

“We still do not know what potential threats the Grimsö Virus may pose to public health. However, based on our observations and previous coronaviruses identified among bank voles, there is good reason to continue monitoring the coronavirus amongst wild rodents,” said Lundkvist

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.