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

Two doses of the Pfizer/BioNTech COVID-19 vaccine provide more than 95% protection against infection, hospitalisation, severe illness, and death, including among the elderly, according to the first national real world assessment of its effectiveness, carried out in Israel,

The study, published in The Lancet, unpicks for the first time the public health benefits of a national vaccination programme. Vaccination was found to be the key driver of a decline in COVID-19 infections in Israel.

The findings are encouraging, but unknowns, notably the duration of immunity to COVID-19 remain. It is also possible that new, vaccine resistant variants could emerge in the future, the authors say.

Lead author, Sharon Alroy-Preis, of the Israel Ministry of Health, said that as the country with the highest proportion of its population vaccinated against COVID-19, Israel provides a unique real-world opportunity to determine the effectiveness of the vaccine. “Until this point, no country in the world had described the national public health impact of a nationwide COVID-19 vaccination campaign. These insights are hugely important because, while there are still some considerable challenges to overcome, they offer real hope that COVID-19 vaccination will eventually enable us to control the pandemic.”

Vaccination with the Pfizer/BioNTech vaccine began amid a surge of infections that led to a national lockdown in Israel on 27th December 2020. Daily infections peaked at 10,213 cases on 20 January 2021, and lockdown was lifted on 7 March 2021.

By 3 April 2021, 72% or 4,714,932 people over 16 years, and 90%, or 1,015,620, of those over 65 years, had received two doses of the Pfizer/BioNTech vaccine.

During the analysis period, there were 232,268 confirmed COVID-19 infections in the country. The most prevalent strain was B.1.1.7, first detected in the UK, which accounted for 94.5% (8,006 of 8,472) of samples tested through Israel’s PCR testing service.

The Pfizer/BioNTech vaccine was highly effective against COVID-19 for all people over the age of 16 years, providing 95.3% protection against infection and 96∙7% protection against death seven days after the second dose. The vaccine is also highly effective in preventing hospitalisation.

Assessing efficacy after one dose of Pfizer/BioNTech vaccine demonstrated the importance of fully vaccinating adults. Protection was considerably lower between seven and 14 days after receiving the first dose, compared to two doses.

The surge in new variants of COVID-19 and an increase in subsequent cases is continuing to have an impact on clinical trials, even though studies are resuming. The total number of disrupted trials has levelled off and the number of clinical trials that have restarted continues to rise, but at a somewhat slower rate than the initial rise.

This implies that sponsors and contract service providers have begun to adjust clinical trial design strategies and are adapting to the new post-COVID-19 environment, according to GlobalData, a data and analytics company.

“Since June 2020, the number of total disrupted trials has been falling slowly; however, this levelled off in October 2020. The majority of current trial disruptions are due to trials impacted by slow enrollment, said Brooke Wilson, associate director, trials intelligence at GlobalData.

Trials that started enrolling before the pandemic, with sites and investigators chosen, but then were suspended due to COVID-19, are “having more success picking up where they left off,” Wilson said.

But overall, the number of trials being impacted by slow enrollment continues to increase.

Methods that could help start or sustain research include virtual visits, phone interviews, self-administration, and remote monitoring. These suggestions could help trials that are being hampered by quarantines, travel limitations, clinical site closures, and interrupted supply chains, especially trials that delayed initiation and trials that are experiencing slow enrollment.

A new report uses lessons learned from the rapid development of COVID-19 vaccines to explore opportunities to overhaul R&D in the field, saying nothing in recent times has underlined the value of investing in basic research as much as the speedy development of effective vaccines.

COVID-19 vaccines are also a testament to the power of partnerships to break down institutional and competitive barriers to scientific collaboration, says the report by the high level Sabin-Aspen vaccine science & policy group. Such success can only become routine if there is a specific effort to bring people together across disciplines, to drive novel research.

To promote this convergence there should be support for a research infrastructure that creates opportunities for novel approaches and risk taking and leverages lessons from adjacent scientific areas, ranging from the chemistry and physics of vaccine formulation, to the immunological basis of protection.

In addition, clinical design is ripe for more efficient and nimbler approaches. Bringing together large datasets and analyses of clinical and laboratory information on infected and vaccinated individuals may make it possible to identify what level of immune response is needed to confer protection, allowing regulatory approval to be based on smaller and faster trials. The use of master protocols could accelerate trials and make it easier to compare the results of one study with those of another, the report says.

The effort to improve vaccine discovery and development and must be accompanied by updated regulatory science and processes, with streamlined preclinical testing, faster, nimbler and more cost-effective trials, and enhanced product scale-up and manufacturing, the group says.

The Danish Health Authority (DHA) said it would not use Johnson & Johnson’s single dose COVID-19 vaccine, following an evaluation by the European Medicines Agency which concluded there is a possible link between rare but severe cases of blood clots and the vaccine.

DHA said the COVID-19 epidemic in Denmark is currently under control and the vaccination rollout is progressing satisfactorily using other vaccines. As a result, it has decided the benefits of using the Johnson & Johnson vaccine do not outweigh the risk of causing serious blood clots.

The decision does mean there will be a four week delay in vaccinating people aged 20 – 39.

“In the midst of an epidemic, this has been a difficult decision to make, especially since we have also had to discontinue using the COVID-19 vaccine from AstraZeneca,” said DHA deputy director general, Helene Probst.

“Taking the present situation in Denmark into account, what we are currently losing in our effort to prevent severe illness from COVID-19 cannot outweigh the risk of causing possible side effects in the form of severe blood clots in those we vaccinate,” Probst said.

Denmark’s national vaccination rollout began more than four months ago and almost everyone in the most vulnerable group of people aged over 65 has been invited, has booked, or has begun the vaccination process.

The decision to continue the rollout without the COVID-19 vaccine from Johnson & Johnson will affect those between 20 and 39 years old, who are facing a delay of up to four weeks.

“Age is the main risk factor for severe illness from COVID-19, and these are younger citizens who are not at risk of becoming seriously ill," said Probst.

The European Medicines Agency said it has started evaluating an application to extend the use of the Pfizer/BioNtech COVID-19 vaccine to include young people aged 12 to 15.

The agency will carry out an accelerated assessment, including results from a large ongoing clinical study involving adolescents from 12 years of age. The evaluation is expected to be completed in June.

Separately, EMA announced it has begun a rolling review of a COVID-19 vaccine developed by the Chinese pharma company, Sinovac Life Sciences. The vaccine contains inactivated SARS-CoV-2 virus, plus an adjuvant that is intended to strengthen the immune response.

The vaccine has been evaluated in four clinical trials conducted in China and overseas, involving 14,572 participants.

An EU-funded study of how entrepreneurs have survived the COVID-19 pandemic, shows most faced significant challenges that threatened the survival of their businesses, but there was resilience in how they navigated the crisis, by being agile, adaptive, exploring new opportunities and using government support.

The study, carried out by researchers at King’s College London, involved surveying over 5,000 entrepreneurs in 23 countries that represent 75% of the world’s economic output. The findings paint a picture of opportunities, but also vulnerabilities of these SME entrepreneurs in the COVID-19 pandemic.

While entrepreneurs were in general optimistic and could see an upside to the pandemic, including long-term positive impacts on their businesses and job creation, it was also clear that many face real challenges to sustain their businesses going forward and that the pandemic is taking a toll on their mental health.

Building on the insights from the survey, the researchers identify five trends and highlight policy actions to support SMEs and entrepreneurs for a thriving post-COVID economy. During the pandemic, most governments were focussed on relief measures, including financial support. This was taken up by SMEs and entrepreneurs when available.

With vaccine programmes being rolled out, policy focus should now shift to how the economic recovery can be aided, the researchers say.

A new piece of research shows that during the pandemic scientists have made increasing the use of preprints to publish their research and these papers are being read more frequently.

This has prompted a cultural shift in how preprints are used and viewed, with the media and the public taking far more interest, according to Jonathon Alexis Coates of Queen Mary University of London, a co author of the paper.

Preprints are free to read, often updated, and most importantly, enable researchers to share their research when it is complete, rather than having to submit to a journal and await acceptance – or rejection – and peer review.

Apart from open access, a benefit is that the process of science is speeding up. Preprints are typically posted within two days of being submitted to a server, in contrast to the months or years that it can take for research to go through peer review, Coates says.

Although many journal publishers have prioritised COVID-19 research and taken down paywalls, on average it still takes 34 times longer for a paper to be published in a journal rather than posting it on a preprint server, which takes 24 - 48 hours).

According to the research, during the first ten months of the pandemic, more than 25% of COVID-19 publications, or 30,260 papers, first appeared as preprints. (That includes this particular paper, which has now appeared in a peer review journal, after earlier being published as a preprint).

COVID-19 preprints were viewed 18.2 times and downloaded 27.1 times more than non-COVID preprints posted during the same ten-months.

COVID-19 preprints are also being used to directly influence policymaking decisions. The World Health Organisation and the European Centre for Disease Control have cited preprints in policy documents during the pandemic. Coates says that in similar policy documents from before COVID-19, preprints don’t appear to have been widely referred to before.

COVID-19 broke the mould of the 9 – 5 day in the office overnight. There have since been many analyses of people’s experiences when they were forced to work from home during lockdown, and now researchers in Denmark have drawn on this to devise a tool that can be used to systematically identify pros and cons when drawing up home working policies.

The researchers, at DTU Management in Lyngby, Denmark, identified six areas they say managers should focus on when developing strategies for remote work in future.

“We’ve examined the pros and cons of working from home among managers and employees in knowledge jobs in eight European countries,” said Christine Ipsen, associate professor at DTU (Technical University of Denmark), who is one of the researchers behind the study.

The tool is based on answers to questionnaires in the eight European countries, completed by people who worked from home during the lockdown from mid-March to mid-May 2020.

“Most people felt that working from home provided benefits in terms of better work/life balance, increased efficiency, and more control over their own work. These three advantages outweighed the three main disadvantages: the inevitable shortcomings of the home office, the greater uncertainty when you don’t meet physically with your boss and colleagues, and finally the reduced access to necessary work tools that are normally available in the office,” Ipsen said.

But it’s not a given that everyone feels positive about working from home. “By analysing employees’ experiences based on the six factors we identified, management can get an overview of what to keep in mind, and when to take action in relation to different employee groups,” said Ipsen.

The researchers found that young people aged 18 to 30 scored higher when it came to work/life balance than employees over the age of 31. On the other hand, young people had more problems with uncertainty about the work compared to older generations, who perceived inadequate tools as a bigger problem.

“It’s about minimising the disadvantages, because the trend we’re seeing shows that people will work more from home in the future, even when [COVID-19] no longer dominates society,” Ipsen said.

Experiences of remote work may change in the future, Ipsen noted. “More studies are needed to look at the six factors over time and in more industries,” she said.

The European Medicines Agency (EMA) and the European Centre for Disease Prevention and Control (ECDC) kicked off a new initiative aimed at strengthening monitoring of the safety, effectiveness and impact of COVID-19 vaccines.

With the ongoing authorisation and rollout of several COVID-19 vaccines in the EU, jointly coordinated, large-scale, EU-wide effectiveness and safety studies are an essential tool to see how novel vaccines perform in real life, according to the two agencies. These studies will generate evidence to support continuous assessment of the benefits and risks of the vaccines and inform decision making on their use in national or regional vaccination strategies.

The move comes after EMA was criticised by member states for not providing explicit advice on the use of AstraZeneca’s and Johnson & Johnson’s vaccines, following its review of rare cases of unusual blood clots. EMA concluded the clots are a rare side effect of the vaccines, but said it was up to national governments to decide how to shape vaccines rollout in response to this finding.

EMA and ECDC will jointly coordinate and oversee a number of observational studies funded from the EU budget and conducted in several European countries. EMA will lead on monitoring safety and ECDC on the effectiveness of vaccines.

This work will be supported by a joint advisory board (JAB) to the two agencies.

“Observational research is an important pillar in the post-marketing surveillance of COVID-19 vaccines and increased EU level collaboration is needed so that member states can join forces and organise large studies that meet the needs of both medicines regulators and national institutes for public health and vaccination,” said Emer Cooke, EMA’s executive director.

“This new model of collaboration brings medicine regulators and public health authorities closer together and establishes processes towards a more permanent, sustainable collaboration platform for monitoring vaccine safety and effectiveness,” said Andrea Ammon, ECDC director.

Pharmaceuticals ingredient manufacturer Evonik said it has delivered the first lipids from its facility in Hanau, Germany, to BioNTech, for the manufacture of the Pfizer/BioNTech COVID-19 vaccine.

The delivery is months earlier than planned, with specialists at the Hanau site setting up the lipid production in just eight weeks. Initially, delivery was scheduled to start in the middle of the year.

"Setting up production at this speed is a great achievement," said Christian Kullmann, chair of Evonik. "Increasing lipid production in Germany will also allow us to further accelerate the manufacturing of larger quantities of the vaccine."

Initial manufacture of the Pfizer/BioNTech vaccine at Pfizer’s plant in Belgium relied on imports of lipids from a manufacturer in the UK, and the head of the EU’s vaccines taskforce Thierry Breton, competition commissioner, has been working to increase EU autonomy and end-to-end control of vaccines supply chains.

As part of its strategic partnership with BioNTech, Evonik produces two different lipids for the Pfizer-BioNTech COVID-19 vaccine. Together with other lipids, they encapsulate to form a lipid nanoparticle, which works as a protective shell around the messenger RNA that carries the genetic code for the spike protein of the virus. Once injected, the mRNA is released to allow the vaccine to take effect.

"This is a complex production process that only a few in the world master," said Thomas Riermeier, head of Evonik's health care business.