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

02 Jun 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.

The European Medicines Agency said it co-chaired a meeting of regulators from around the world to discuss the global regulatory response to the COVID-19 Omicron variant.

The goal of the meeting was to review available evidence for the effectiveness of the approved COVID-19 vaccines against the Omicron and reach alignment on the key regulatory requirements to support development of a possible adapted vaccine.

Emer Cooke, EMA executive director, told the meeting the discussion was not only about the regulatory response to Omicron, but is also part of setting the scene for a more strategic discussion about what types of vaccines might be needed in the long-term to adequately manage COVID-19.

“These decisions are not for regulators alone. Collaboration is needed across all the actors in this space, including public health decision makers at national, regional and global level,” Cooke said.

While most available data suggest that the approved COVID-19 vaccines are losing effectiveness in protecting against infection and mild disease, they continue to provide high protection against serious infections.

EMA said details on the discussions and the outcomes of the meeting will be published in the coming days. Meanwhile, the agency said its preliminary assessment of the available data indicates COVID-19 vaccines remain effective against severe disease and hospitalisation caused by the Omicron variant.

Although Omicron appears to be more infectious than other variants, studies from South Africa, UK and some EU countries show a lower risk of being hospitalised after infection with Omicron; based on these studies, the risk is currently estimated to be between a third and half of the risk with the Delta variant.

However, results from recently published studies show that vaccine effectiveness against symptomatic disease is lower for Omicron than for other variants and tends to wane over time. As a result, more vaccinated people are likely to develop breakthrough disease due to Omicron.

The latest evidence, which includes real-world effectiveness data, also suggests that people who have had a booster dose are better protected than those who have only received their primary course.

EMA said it will continue to review data on vaccine effectiveness and severity of the disease. The outcome of these assessments may impact future vaccination strategies recommended by experts in the EU.

A collaboration between BioNTech and UK artificial intelligence specialist Instadeep has led to the development of a new computational method that analyses worldwide genome sequencing data to pick out high-risk variants of SARS-CoV-2.

The Early Warning System (EWS), based on artificial intelligence (AI) calculated immune escape and fitness metrics, combines structural modeling of the spike protein by which the virus enters host cells, and AI algorithms, to quickly flag potential high-risk variants. It can pick up sequences uploaded to SARS-CoV-2 data repositories within less than a day, based on metrics scoring their fitness and their immune escape properties.

The two companies validated these predictions using experimental data generated in-house and publicly available data.

During a trial period, the system identified more than 90% of the World Health Organisation (WHO)-designated variants. The WHO-designated variants of concern, Alpha, Beta, Gamma, Theta, Eta and Omicron were detected by the EWS in the same week as their sequences were first uploaded, with the Omicron variant ranked as a high-risk variant the same day its sequence became available.

The results from the study underline that the EWS is capable of evaluating new variants in minutes and risk-monitoring variant lineages nearly in real-time. It is also fully scalable as new variant data becomes available.

“With the advanced computational methods we have been developing over the past months we can analyse sequence information of the spike protein and rank new variants,” said Ugur Sahin, CEO and co-founder of BioNTech. “Early flagging of potential high-risk variants could be an effective tool to alert researchers, vaccine developers, health authorities and policy makers, thereby providing more time to respond to new variants of concern.”

The data published as a pre-print is the result of a collaboration established between BioNTech and InstaDeep in November 2020. As part of the collaboration, the companies formed a joint AI innovation lab in London and Mainz, Germany.

A new molecule developed by researchers at Helsinki University protects against SARS-CoV-2 infection for at least eight hours, and in contrast to vaccines, is effective immediately after administration as a nasal spray.

“In animal models, nasally administered TriSb92 offered protection against infection in an exposure situation where all unprotected mice were infected,” said Anna Makela, first author of the study, which has been
published as a preprint.

The molecule, TriSb92, inhibits the functioning of the spike protein on the surface of the SARS-CoV-2 virus.

“Targeting this inhibitory effect of TriSb92 to a site on the coronavirus spike protein common to all variants of the virus makes it possible to effectively inhibit the ability of all known variants, Omicron included, to infect people,” Makela said.

The European Medicines Agency said it has started evaluating Pfizer’s oral antiviral drug Paxlovid in the treatment of mild-to-moderate COVID-19 in adult and adolescent patients who are at high risk of progression to severe disease under a reduced timeline, and could issue an opinion within weeks.

The expedited timeframe is possible because EMA has already started a rolling review, which included in vitro, animal and clinical studies, including one looking at use of Paxlovid in non-hospitalised, unvaccinated patients with COVID-19, who had symptomatic disease and at least one underlying condition putting them at risk of severe disease.

Paxlovid reduces the ability of SARS-CoV-2 to cause serious infections by blocking the activity of an enzyme the virus needs to multiply.

A new study has provided direct evidence of a protective role for T cells generated in response to common colds caused by coronaviruses.

While previous studies have shown that T cells induced by other coronaviruses can recognise SARS-CoV-2, the research by scientists at Imperial College London is the first to show the presence of these T cells at the time of SARS-CoV-2 exposure influences whether someone becomes infected.

The researchers also say their findings could inform the design of a second generation, universal vaccine that could prevent infection from current and future SARS-CoV-2 variants, including Omicron.

Rhia Kundu, first author of the study said, “Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why. We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection.”

The study, which started in September 2020 when most people in the UK had neither been infected nor vaccinated against SARS-CoV-2, involved 52 people who lived with someone with PCR-confirmed SARS-CoV-2 infection, and who had therefore been exposed to the virus. The participants did PCR tests at the outset and 4 and 7 days later, to determine if they developed an infection.

Blood samples from the 52 participants taken within 1-6 days of them being exposed to the virus were analysed for pre-existing T cells induced by previous common cold coronavirus infections that also cross-recognise proteins of the SARS-CoV-2 virus.

The researchers found that there were significantly higher levels of these cross-reactive T cells in the 26 people who did not become infected, compared to the 26 people who did become infected.

These T cells targeted internal proteins within the SARS-CoV-2 virus, rather than the spike protein on the surface of the virus.

The current COVID-19 vaccines do not induce an immune response to these internal proteins, which researchers say, offer a new vaccine target that could provide long-lasting protection, because T cell responses persist longer than antibody responses, which wane within a few months of vaccination.

Dutch biotech Intravacc has formed a partnership with Leiden University Medical Centre (LUMC) to develop and evaluate a new nasal spray COVID-19 vaccine in a clinical phase I/II study.

The vaccine, Nanovac, is based on microscopic soluble nanospheres, containing synthetic mini proteins administered as a nasal spray, to directly protect the upper respiratory tract including nasal passages and throat, before the virus reaches the lungs.

The design and route of administration makes the vaccine broadly protective, harnessing both arms of the immune system against COVID-19.

A team led by Luis Cruz at LUMC’s Translational Nanobiomaterials and Imaging department has spent more than a year working on the nasal spray vaccine. Preclinical studies in animals showed positive results.

The phase I/II clinical study is led by Leo Visser of the Infectious Diseases Department at LUMC.

Nanovac is intended to protect against current and future COVID-19 variants, by generating an immune reaction not only against the spike protein the virus uses to enter human host cells, but also other conserved epitopes derived from distinct coronavirus proteins.

In addition, the product includes an adjuvant to enhance the immune response it generates.

Intravacc says the vaccine can be produced rapidly in large quantities at a lower cost than existing vaccines, and can be stored at room temperature.

US biotech Gritstone Bio has announced positive phase I clinical data from the first cohort of participants in the UK trial of its self-amplifying mRNA (samRNA) vaccine, demonstrating both strong neutralising antibody responses to the spike protein and robust T cell responses.

The vaccine is being assessed for use as a booster against SARS-CoV-2 in healthy adults who previously received two doses of AstraZeneca's first-generation COVID-19 vaccine.

Andrew Allen, CEO of Gritstone said, “As we have seen with the Omicron variant, viral surface proteins such as spike are mutating at a high rate, leaving the immunity provided by spike-dedicated vaccines vulnerable to variants containing numerous spike mutations. We designed our COVID-19 vaccines to drive broad CD8+ T cell immunity, an additional key layer of protection against viruses.”

Andrew Ustianowski, lead investigator for the study at Manchester University and clinical lead for the National Institute for Health Research COVID-19 vaccine research programme, said the initial  data strongly support the approach to T cell priming and potent neutralising antibody generation with a dose of samRNA potentially up to 10-fold lower than that required for first generation mRNA vaccines.

“We are increasingly realising the importance of both the T cell response and non-spike protein targets for protection against severe disease, hospitalisation, and death, and to allow protection against current and future variants of the virus,” Ustianowski said.

The trial is ongoing in the UK.

A group of over 65 leading institutional investors is calling on COVID-19 vaccine manufacturers to move quickly to increase the availability and deployment of vaccinations around the world.

An investor statement has been drawn up to that end under the leadership of the Dutch fund Achmea Investment Management and letters have been sent to pharmaceutical companies asking them to make the global availability of vaccines part of the remuneration policy of managers and directors.

In total, the more than 65 asset managers, pension funds and insurers who have joined the initiative represent total assets of €3,000 billion.

The World Health Organisation (WHO) has said affordable vaccination for the whole world is vital to combat the pandemic, from both the humanitarian and economic viewpoints. The WHO has outlined a clear path to achieving this and the institutional investors want pharmaceutical companies to make these WHO targets part of their remuneration policy.

Rogier Krens, chief investment officer of Achmea said, “We will only be able to get this pandemic under control by working together. Our view is that pharmaceutical companies have a duty to do their utmost on this, but unfortunately we see that they are lagging behind. In addition, the business case is clear: new variants threaten the recovery of economies around the world.”

While physicists have long posted preprints of their research in advance of peer review, biologists have held back. The COVID-19 pandemic has changed that, with preprints in the biomedical sciences being posted and accessed at unprecedented rates and drawing widespread attention from the general public, press and policymakers for the first time.

This has sharpened longstanding questions about the reliability of information shared prior to journal peer review. In particular, do the findings shared in preprints typically withstand the scrutiny of peer review, or are conclusions likely to change in the version of record?

Researchers have assessed preprints from the bioRxiv and medRxiv servers that had been posted and subsequently published in a journal through 30th April 2020, during the initial phase of the pandemic response. They used a combination of automatic and manual annotations to quantify how an article changed between the preprinted and published version.

They found that the total number of figures and tables hardly differed between preprint and published articles. 7.2% of non-COVID-19 and 17.2% of COVID-19-related abstracts changed from the preprint to the peer reviewed journal paper, but the majority of these changes do not qualitatively change the overall conclusions that were drawn.

The data analysing abstracts suggests that the main conclusions of 93% of non-COVID-related life sciences articles do not change from their preprint to final published versions, with only one out of 184 papers in the analysis contradicting a conclusion made by its preprint.

“Our data provides confidence in the use of preprints for dissemination of research,” the researchers conclude.

With the Omicron variant of SARS-CoV-2 spreading at an alarming rate and poised to replace the Delta variant, German scientists led by Stefan Pöhlmann and Markus Hoffmann from the German Primate Centre at the Leibniz Institute for Primate Research in Göttingen have assessed the efficiency of vaccines and therapeutic antibodies against Omicron, looking at how efficiently it is neutralised by antibodies from recovered and vaccinated people.

The team was able to show that antibodies from people who recovered from a natural infection hardly inhibit the Omicron variant. Antibodies produced after two doses of the Pfizer/BioNTech vaccine also showed significantly reduced efficacy.

Better inhibition was observed after Pfizer boosters and after heterologous vaccination with the AstraZeneca and Pfizer vaccines.

In common with other researchers, the German scientists found that most of the therapeutic antibodies evaluated in the study are not effective against the Omicron variant.

Currently, combinations of the antibodies Casirivimab and Imdevimab, and Etesevimab and Bamlanivimab are used to treat COVID-19, but these drugs do not work against Omicron. Only one antibody, GlaxoSmithKline’s Sotrovimab, retains its effect.

"Our cell culture studies suggest that most antibodies currently available for COVID-19 therapy will be ineffective against Omicron. Sotrovimab is an exception and could become an important treatment option for Omicron-infected patients," Hoffmann said.

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