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

30 Jun 2022 | Live 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.

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.”

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.

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.

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.

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.

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.

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.

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.

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.

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.

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