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

As of 29 November 2021, 33 confirmed cases of the Omicron variant of concern have been reported in Austria, Belgium, Czechia, Denmark, Germany, Italy, Netherlands and Portugal, according to the European Centre for Disease Control and Surveillance (ECDC).

A number of probable cases have also been reported that are still under investigation. All confirmed cases have a history of travel to African countries, with some having taken connecting flights at airports between Africa and Europe.

Separately, Scotland’s health minister Humza Yousaf said six cases reported in Scotland were not all related to travel, indicating there may be some community transmission.

ECDC said for those cases for which there is information available severity was either asymptomatic or mild. No severe cases and no deaths have been reported among Omicron cases so far.

In collaboration with academic groups in South Africa and around the world, Johnson & Johnson is now evaluating the effectiveness of its COVID-19 vaccine against the new and rapidly spreading Omicron variant, testing blood serum from participants in completed and ongoing booster studies to look for neutralising activity against the variant.

At the same time, the company said it is working on an Omicron-specific variant vaccine, which it will advance as needed.

Omicron highlights the importance of continued surveillance, testing and vaccination to prevent hospitalisation and deaths from COVID-19, said Mathai Mammen, global head of Janssen Research & Development at Johnson & Johnson. “We will not be complacent. Building on our long-term collaboration with scientists on the ground in South Africa and the ongoing real world effectiveness studies being conducted with the Johnson & Johnson COVID-19 vaccine, we will work together to generate new data on Omicron.”

“In parallel, we have begun work to design and develop a new vaccine against Omicron and will rapidly progress it into clinical studies if needed,” Mammen said.

There is considerable uncertainty related to the transmissibility, vaccine effectiveness, risk for reinfections and other properties of the Omicron variant of SARS-CoV-2, the European Centre for Disease Control said in its assessment of the threat of the new variant.

However, given its immune escape potential and potentially increased transmissibility advantage compared to Delta, “We assess the probability of further introduction and community spread in [Europe] as ‘high’,” CDC said.

With the number of COVID-19 infections caused by the Delta variant already on the rise in Europe before the emergence of Omicron was announced by South Africa’s Ministry of Health on Friday 26 November, the impact of the introduction and possible further spread of Omicron could be ‘very high’, ECDC added.

Based on the mutation profile of Omicron, partial immune escape is likely, and genomic surveillance remains of utmost importance for early detection of the presence of this variant, to enable the following of epidemiological trends and guide containment measures.

Following on from the announcement of the emergence of the new variant, its naming and designation by the World Health Organization as a variant of concern, cases have been reported from across Europe and in Canada.

Moderna said it is testing three existing COVID-19 vaccine booster candidates against the Omicron variant and also developing a new variant-specific vaccine candidate against the SARS-CoV-2 variant of concern that was first identified in South Africa.

Omicron includes mutations seen in the Delta variant that are believed to increase transmissibility, and mutations seen in the Beta and Delta variants that are believed to promote immune escape, making vaccines less effective. The combination of mutations represents a significant potential risk of the waning of natural and vaccine-induced immunity and a booster dose of an authorised vaccine represents the only currently available strategy for boosting waning immunity.

Moderna is working to test the ability of the current vaccine dose to neutralise the Omicron variant and data is expected in the coming weeks. The company has also tested a higher dose booster in healthy adults and has completed dosing of 306 participants in a safety and immunogenicity study of this high dose.

In addition, Moderna is studying two multi-valent booster candidates in the clinic, that are designed to anticipate mutations such as those that have emerged in the Omicron variant. The first candidate includes several mutations present in Omicron that are also present in the Beta variant, while the second includes many of the mutations present in Omicron that also occur in both the Beta and Delta variants.

Now Moderna will rapidly advance an Omicron-specific booster candidate and says it has demonstrated the ability to advance new candidates to clinical testing in 60-90 days.

“The mutations in the Omicron variant are concerning and for several days we have been moving as fast as possible to execute our strategy to address this variant,” said Stéphane Bancel, CEO of Moderna. “We have three lines of defence that we are advancing in parallel: we have already evaluated a higher dose booster of mRNA-1273; second, we are already studying two multi-valent booster candidates in the clinic that were designed to anticipate mutations such as those that have emerged in the Omicron variant and data is expected in the coming weeks; and third, we are rapidly advancing a Omicron-specific booster candidate,” he said.

The protection two doses of the Pfizer/BioNTech vaccine provide from COVID-19 infection wanes with time, suggesting a third booster dose might be necessary, according to an Israeli study published in the British Medical Journal.

Israel was one of the first countries to roll out a large scale COVID-19 vaccination campaign in December 2020, but has seen a resurgence of infections since June 2021. 

The research, carried out by the Research Institute of Leumit Health Services in Tel Aviv, confirms that the Pfizer-BioNTech vaccine provided excellent protection in the initial weeks after vaccination, but suggests that protection wanes for some individuals with time.

Examining the time elapsed since vaccination and risk of infection is needed to inform decisions about the need for a third injection, and its preferred timing.

The researchers examined electronic health records of 80,057 adults who had a PCR test for COVID-19 at least three weeks after their second injection. Of these 80,057 participants, 7,973 (9.6%) had a positive test result. These individuals were then matched to negative controls of the same age and ethnic group who were tested in the same week. 

The rate of positive results increased with time elapsed since a second dose. Across all age groups 1.3% of participants tested positive 21-89 days after a second dose, but this increased to 2.4% after 90-119 days; 4.6% after 120-149 days; 10.3% after 150-179 days; and 15.5% after 180 days or more.

After taking account of other potentially influential factors, the researchers found a significantly increased risk of infection with time elapsed since a second dose. 

Compared with the initial 90 days after a second dose, the risk of infection across all age groups was 2.37-fold higher after 90-119 days; 2.66-fold higher after 120-149 days; 2.82-fold higher after 150-179 days; and 2.82-fold higher after 180 days or more.

The researchers say they cannot rule out the possibility that other unmeasured factors, such as household size, population density, or virus strain may have had an effect. However, this was a large study of people who all received the same vaccine, and they were able to carry out detailed analysis of the data, suggesting the results are robust.

They conclude that in individuals who received two doses of the Pfizer/BioNTech vaccine, protection decreased over time, and the risk of breakthrough infection increased progressively compared with the protection provided during the initial 90 days.

The results suggest booster doses are warranted, the researchers say.

A new statistical analysis suggests that COVID-19 became more lethal in the UK in late 2020, but points to multiple factors, and not just the rise of the more infectious Alpha variant of the virus first identified in Kent, that were to blame.

Studying how the lethality of COVID-19 has changed over time in different regions could help guide efforts to address this disease. While preliminary evaluations of infection and mortality data suggest that COVID-19 may have become more lethal in the UK in late 2020, more rigorous analyses have been lacking.

To explore this further, Patrick Pietzonka and colleagues at the Department of Applied Mathematics and Theoretical Physics, Cambridge University, used Bayesian inference, a technique that enabled them to draw statistically stronger conclusions about lethality from weekly data on the number of cases and the number of deaths due to COVID-19 in the UK.

Specifically, the researchers compared predictions from different mathematical simulations of COVID-19 spread and deaths, some of which incorporated increased lethality.

The analysis suggests that in late autumn of 2020 COVID-19 did indeed become more lethal in the UK, meaning that the probability that an infected person would die from the disease increased.

It was thought this increase in lethality was driven by the Alpha variant of the SARS-CoV-2 virus, which was more infectious than previous variants.

However, the new analysis suggests that lethality increased to a greater degree than the Alpha variant would have accounted for, and that the increase in lethality began before Alpha became widespread.

These findings suggest that, while the Alpha variant contributed to increased lethality in late 2020, other factors were also in play.

Further research will be needed to identify those factors, but Pietzonka and colleagues suggest they may include both the increased strain on healthcare services and the seasonal cycle in the severity of viruses that is seen in other respiratory diseases like the common cold and flu.

Scientists in the Department of Virology at the Institut Pasteur in Paris have identified coronaviruses closely related to SARS-CoV-2 from two bats sampled in Cambodia more than a decade ago.

The discovery, described in Nature Communications,  along with the recent detection of the closest ancestors of SARS-CoV-2 known to date in cave-dwelling bats in Laos, indicates that SARS-CoV-2-related viruses that cause COVID-19 have a much wider geographic distribution than previously reported, and further supports the hypothesis that the pandemic originated via spillover of a bat-borne virus.

The researchers used metagenomic sequencing to identify the nearly identical viruses in two horseshoe bats, Rhinolophus shameli, originally sampled in 2010. The findings suggest that SARS-CoV-2 related viruses are likely circulate via multiple Rhinolophus species.

The limited understanding of the geographic distribution of SARS-CoV possibly reflects a lack of sampling in southeast Asia, or at least across the Greater Mekong subregion, which encompasses Myanmar, Laos, Thailand, Cambodia, Vietnam, and the Yunnan and Guanxi provinces of China, the researchers say.

In addition to bats, the researchers note that pangolins and certain species of cat, civet, and weasels found in this region are readily susceptible to SARS-CoV-2 infection, and might represent intermediary hosts for transmission to humans.

These findings underscore the importance of increasing surveillance of pathogens in wildlife in southeast Asia, which hosts a high diversity of wildlife and where trade in wildlife puts humans in direct contact with wild hosts of SARS-like coronaviruses.

The European Medicines Agency has started evaluating an application for approval of the oral antiviral drug Lagevrio, developed by Merck Sharp & Dohme.  

The agency said it will assess the drug under a reduced timeline and could issue an opinion within weeks, because it has already reviewed a substantial portion of the data in a rolling review.

These data include interim results from the main study on the effects of Lagevrio in non-hospitalised, unvaccinated patients with at least one underlying condition putting them at risk of severe COVID-19. The hope is that having an oral treatment people can take at home will reduce the severity of infection and avoid the need for admission to hospital.

Lagevrio reduces the ability of SARS-CoV-2 virus to multiply in the body by introducing mutations in the genetic material of SARS-CoV-2 during replication.

EMA previously issued advice to member states on use of Lagevrio in advance of formal approval on 19 November 2021.

In other COVID-19 regulatory news, EMA recommended granting an extension of indication for Pfizer/BioNTech’s COVID-19 vaccine, to include use in children aged 5 to 11. The vaccine is already approved for use in children aged 12 and above.

A team of researchers led by the University of Zurich has discovered previous antibody responses to other, harmless, coronaviruses contributes to SARS-CoV-2 immunity.

“People who have had strong immune responses to other human coronaviruses also have some protection against SARS-CoV-2 infection,” said Alexandra Trkola, head of the Institute of Medical Virology at the university.

In their study, the researchers used a specially developed assay to analyse antibody levels against four other human coronaviruses in 825 blood samples taken before SARS-CoV-2 emerged. They also examined 389 samples from donors infected with SARS-CoV-2.

Combining these analyses with computer-based models enabled the team to precisely predict how well the antibodies would bind to and neutralise invading viruses.

The researchers demonstrated that people who caught SARS-CoV-2 had lower levels of antibodies against coronaviruses that cause common colds, compared to uninfected people. In addition, people with high levels of antibodies against harmless coronaviruses were less likely to have been hospitalised after catching SARS-CoV-2.

“Our study shows that a strong antibody response to human coronaviruses increases the level of antibodies against SARS-CoV-2. So someone who has gained immunity to harmless coronaviruses is therefore also better protected against severe SARS-CoV-2 infections,” says Trkola.

This type of immune response, referred to as cross-reactivity, also occurs with T cell responses, the second line of defense against infections.

“Even though the protection isn’t absolute, cross-reactive immune responses shorten the infection and reduce its severity. And this is exactly what is also achieved through vaccination, just much, much more efficiently,” said Trkola.

It is not yet known whether this cross-reactivity also works in the opposite direction and if immunity to SARS-CoV-2 achieved through vaccination also offers protection against other human coronaviruses.

New data on the Pfizer/BioNTech vaccine shows it has 100% efficacy against COVID-19 in adolescents aged 12 - 15, with no serious safety concerns identified, paving the way for the companies to apply for approval in this age group.

The adverse event profile was generally consistent with other clinical safety data for the vaccine, with no serious safety concerns observed in individuals with at least 6 months of safety follow-up after the second dose.

 “These additional data provide further confidence in our vaccine’s safety and effectiveness profile in adolescents. This is especially important as we see rates of COVID-19 climbing in this age group in some regions, while vaccine uptake has slowed,” said Albert Bourla, CEO of Pfizer.

Results from this analysis of 2,228 trial participants build upon and confirm previously released data and demonstrate strong protection against COVID-19. From the 30 confirmed symptomatic cases of COVID-19 in the trial with and without evidence of prior infection with SARS-CoV-2, 30 cases of COVID-19 were in the placebo group and 0 cases were in the Pfizer/BioNTech vaccine group.