LIVE BLOG: R&D response to COVID-19 pandemic

19 May 2022 | Live Blog
Covid 19 blog

The coronavirus pandemic is disrupting universities and research institutes across the world. But the same institutions are also working very hard to find out how the disease can be stopped and its effects mitigated.

Follow this live blog for the latest updates on how the crisis is impacting research and innovation, and what governments, funders, companies, universities, associations and scientists are doing to stop or cope with the pandemic.

You can read the full archive of this blog here and here.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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