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.

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.

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.

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.

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 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.  

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.

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.

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 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.

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.

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