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

26 Oct 2021 | 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 has changed its recommendations on booster doses of the Pfizer/BioNTech COVID-19 vaccine, saying boosters “may be considered” at least six months after the second dose for people aged 18 years and older.

This is an about turn for EMA, which on 2 September put out a joint statement with the European Centre for Disease Control, saying evidence on vaccine effectiveness and duration of protection showed that all vaccines authorised in the EU remained effective in preventing COVID-19-related hospital admissions, severe disease and death.

The change is based on the evaluation of data showing a rise in antibody levels when a booster dose of the Pfizer vaccine is given approximately six months after the second dose in people from 18 to 55 years old.

A number of countries in Europe have gone ahead with booster programmes despite EMA’s emergency use authorisation for Pfizer’s vaccine not specifying it is safe and effective when used in this way.

EMA said the risk of inflammatory heart conditions or other very rare side effects after a booster is not known and is being carefully monitored. More information about the booster recommendations for Pfizer’s vaccine will be available in the updated product information.

EMA is also currently evaluating data to support a booster dose for Moderna’s COVID-19 vaccine.

At the same time, EMA said an extra dose of either Pfizer or Moderna’s vaccines may be given to people with severely weakened immune systems, at least 28 days after their second dose.

The recommendation comes after studies showed that an extra dose of these vaccines increased the ability to produce antibodies against the SARS-CoV-2 virus in organ transplant patients with weakened immune systems.

As yet, there is no direct evidence that the ability to produce antibodies in these patients protects against COVID-19, but it is expected that the extra dose would increase protection at least in some patients. The product information of both vaccines will be updated to include this recommendation.

Real world US data shows two doses of the Pfizer/BioNTech vaccine are 90% effective at preventing COVID-19 hospital admission across all variants of the SARS-CoV-2 virus, including Delta, for at least six months, according to a study published in The Lancet.

However, over time, two doses are not so good at preventing infections, with effectiveness declining steadily, from 88% within one month of receiving two vaccine doses, to 47% after six months.

The researchers say this study underscores the importance of improving COVID-19 vaccination rates worldwide and monitoring vaccine effectiveness to determine which populations should be prioritised to receive boosters.

“Our study confirms that vaccines are a critical tool for controlling the pandemic and remain highly effective in preventing severe disease and hospitalisation, including from Delta and other variants of concern. Protection against infection does decline in the months following a second dose,” said Sara Tartof, of the Kaiser Permanente Southern California Department of Research & Evaluation, one of the study authors. 

The researchers analysed 3.4 million electronic health records from the Kaiser Permanente Southern California health system between 4 December 2020, and 8 August 2021. During this time, 5.4% (184,041 people) were infected with SARS-CoV-2. Among those who were infected, 6.6% (12,130) were hospitalised. The average time since being fully vaccinated was between three to four months.

Whole genome sequencing showed the Delta variant comprised 28% of the overall proportion of positive sequences. During the study period, the proportion of positive cases in the US attributed to Delta increased from 0.6% in April 2021 to nearly 87% by July 2021, confirming the Delta variant had become the dominant strain.

Vaccine effectiveness against Delta infections at one month after two doses of vaccine was 93% and fell to 53% after four months. Effectiveness against other variants one month after receiving two doses was 97% and declined to 67% after four months.

The researchers did not observe a difference in the rate of waning between SAR-CoV-2 variant type, suggesting reduced protection from infection was similar regardless of the variant identified and therefore that declining effectiveness is a result of waning vaccine effect affecting all strains in circulation, rather than a variant that is insensitive to the vaccine.

The safety committee of the European Medicines Agency has concluded that there is a possible link between rare cases of venous thromboembolism (VTE) and Johnson & Johnson’s single dose COVID-19 vaccine.

VTE occurs when a blood clot forms in a deep vein, usually in a leg, arm or groin, and travels to the lungs, blocking the blood supply, with possible life-threatening consequences.

This safety issue is distinct from another very rare side effect, of thrombosis with thrombocytopenia syndrome, when blood clots occur despite a low level of the platelets that cause blood to clot. 

VTE was included in EMA’s risk management plan for Johnson & Johnson’s COVID-19 vaccine, because a higher proportion of cases of VTE observed within the vaccinated group versus the placebo group in the large clinical study which was used to authorise the vaccine.

EMA has now reviewed new data from this study, as well as new evidence from another large clinical trial. In the second study there was no increase in venous thromboembolic events among individuals who received the Johnson & Johnson vaccine. However, EMA also reviewed real world data from vaccination campaigns, and when taking all evidence into account, the safety committee concluded there is a “reasonable possibility” rare cases of VTE are linked to this vaccine .

EMA is recommending listing VTE as a rare side effect of the Johnson & Johnson vaccine in the product information, together with a warning to raise awareness among healthcare professionals and people receiving the vaccine, especially those who may have an increased risk of VTE.

The safety committee also assessed cases of immune thrombocytopenia (ITP) - in which the immune system mistakenly targets blood platelets that are needed for normal blood clotting - that have been reported following vaccination with Johnson & Johnson’s and AstraZeneca’s Covid-19 vaccines.

As a result, EMA recommended updating the product information of both vaccines to include ITP as an adverse reaction with an unknown frequency.

A total of 37% of people had at least one long-COVID symptom diagnosed in the 3-6 month period after COVID-19 infection, with the commonest symptoms being breathing problems, abdominal symptoms, fatigue, pain and anxiety/depression.

Researchers at Oxford University investigated long COVID symptoms in over 270,000 people recovering from COVID-19 infection, using patient records from the US TriNetX network, which holds records of 81 million people.

In all, 57% of patients with a recorded diagnosis of COVID-19 subsequently presented to their doctors with symptom(s) of long COVID between 0 – 6 months after infection. More than a third (37%) did not report until three to six months after they contracted COVID-19, indicating they are not persisting acute symptoms. The researchers say it may be that new symptoms emerge some time after initial infection.

Severity of infection, age, and sex, affected the likelihood of long-COVID symptoms, with long-COVID symptoms more frequent in those who had been hospitalised. They were also slightly commoner in women. There was no difference seen between people of different ethnicities.

Older people and men had more breathing difficulties and cognitive problems, whereas young people and women had more headaches, abdominal symptoms and anxiety/depression. Many patients had more than one long-COVID symptom, and symptoms tended to co-occur more as time progressed.

The study, published in PLOS Medicine, does not explain what causes long-COVID symptoms, or say how severe they are, or how long they will last.

Max Taquet, of Oxford University, who led the analysis said, “The results confirm that a significant proportion of people, of all ages, can be affected by a range of symptoms and difficulties in the six months after COVID-19 infection. These data complement findings from self-report surveys, and show that clinicians are diagnosing patients with these symptoms. We need appropriately configured services to deal with the current and future clinical need.”

Research of different kinds is urgently needed to understand why not everyone recovers rapidly and fully from COVID-19, said Paul Harrison, who headed the study. “We need to identify the mechanisms underlying the diverse symptoms that can affect survivors. This information will be essential if the long-term health consequences of COVID-19 are to be prevented or treated effectively,” he said.

The European Medicines Agency has started evaluating an application for the use of a booster dose of Spikevax, Moderna’s COVID-19 vaccine, to be given at least 6 months after the second dose in people aged 12 years and older.

Booster doses would be given to vaccinated people who have completed their primary vaccination, to restore protection after it has waned.

EMA said it will carry out an accelerated assessment of data submitted, including results from an ongoing clinical trial. Based on this review, it will recommend whether the product information should be updated to say booster doses are appropriate.

While it is looking at the file, EMA and the European Centre for Disease Prevention and Control (ECDC) have both said they do not consider the need for COVID-19 vaccine booster doses to be urgent in the general population, EMA’s stance is that it is evaluating Moderna’s application to ensure evidence is available to support further doses as necessary. 

Advice on how vaccinations should be given remains the prerogative of immunisation experts in each EU member state. EMA said member states “may already consider preparatory plans” for giving boosters and additional doses.

Spikevax is currently authorised for use in people aged 12 and older.

The COVID-19 pandemic has triggered life expectancy losses not seen since World War 2 in western Europe, and which exceed those in central and eastern Europe following the break up of the Soviet Union, according to new research.

The researchers brought together a dataset on mortality from 29 countries, spanning most of Europe, the US and Chile, for which official death registrations for 2020 have been published. In 27 of the 29 countries there were reductions in life expectancy in 2020, and at a scale which wiped out years of progress on mortality, according to a paper published in the International Journal of Epidemiology.

Women in 15 countries and men in 10 countries were found to have a lower expectancy at birth in 2020 than in 2015, a year in which life expectancy was already negatively affected by a significant flu season.

The study was led by scientists at Oxford University’s Centre for Demographic Science. Author José Manuel Aburto said, “For western European countries such as Spain, England and Wales, Italy, Belgium, among others, the last time such large magnitudes of declines in life expectancy at birth were observed in a single year was during World War 2.”

The scale of the life expectancy losses was sobering across most countries studied, with twenty two countries having losses in life expectancy greater than six months in 2020. “Females in eight countries and males in 11 countries experienced losses larger than a year,” Aburto said. “To contextualise, it took on average 5.6 years for these countries to achieve a one year increase in life expectancy recently. [That] progress [was] wiped out over the course of 2020 by COVID-19.”

Across most of the 29 countries, males saw larger life expectancy declines than females. The largest drop was observed among males in the US, who saw a decline of 2.2 years relative to 2019 levels, followed by males in Lithuania, where 1.7 years was wiped off life expectancy.

Another author, Ridhi Kashyap said the large declines in life expectancy observed in the US can partly be explained by the notable increase in mortality at working ages observed in 2020. “In the US, increases in mortality in the under 60 age group contributed most significantly to life expectancy declines, whereas across most of Europe increases in mortality above age 60 contributed more significantly,” Kashyap said.

In addition to these age patterns, the analysis reveals that most life expectancy reductions across different countries were attributable to official COVID-19 deaths.

“While we know that there are several issues linked to the counting of COVID-19 deaths, such as inadequate testing or misclassification, the fact that our results highlight such a large impact that is directly attributable to COVID-19 shows how devastating a shock it has been for many countries,” said Kashyap. “We urgently call for the publication and availability of more disaggregated data from a wider range of countries, including low- and middle-income countries, to better understand the impacts of the pandemic globally.”

Life expectancy refers to the average age to which a newborn will live if current death rates continued for their whole life. It does not predict an actual lifespan, but rather provides a snapshot of current mortality conditions. This allows for a comparison of the size of the mortality impacts of the pandemic between different countries and populations.

Researchers at the Institute of Medical Virology at Goethe-University, Frankfurt am Main, and at the School of Biosciences at Kent University in the UK have identified a protein they say may critically contribute to severe forms of COVID-19.

They found that the infection of human cells with SARS-CoV-2 virus resulted in increased levels of CD47, a protein found on the cell surface. CD47 acts as a ‘do not eat me’ signal to the immune system, protecting cells from being destroyed. Virus-induced CD47 on the surface of infected cells is thought to protect them from immune system recognition, enabling the production of larger amounts of virus, resulting in more severe disease.

Well-known risk factors for severe COVID-19 such as older age and diabetes are associated with higher CD47 levels. High CD47 levels also contribute to high blood pressure, which is a large risk factor for COVID-19 complications such as heart attack, stroke, and kidney disease.

The researchers say their data suggest that age and virus-induced high CD47 levels contribute to severe COVID-19 by preventing an effective immune response and increasing disease-associated tissue and organ damage. Drugs targeting CD47 are in development so this discovery may result in improved COVID-19 therapies.

Martin Michaelis, professor of molecular medicine at Kent University, said, “We may have identified a major factor associated with severe COVID-19. This is a huge step in combatting the disease and we can now look forward to further progress in the design of therapeutics.”

Jindrich Cinatl of the Institute of Medical Virology, Goethe-University, said the additional insights into the disease processes underlying COVID-19 may help in the design of better therapies. “Through this avenue, we have achieved a major breakthrough and exemplified that the fight against the disease continues.”

An international group of scientists led by the La Jolla Institute for Immunology in the US have published a detailed map of where therapeutic antibodies bind to SARS-CoV-2, which they say will guide the development of more effective COVID-19 antibody therapies and help develop effective vaccines against viral variants.

The researchers say the findings, published in Science, propel COVID-19 research in three key ways. Hundreds of antibodies contributed by over 50 different organisations around the world were classified and mapped to shows exactly where each one binds on the spike protein of SARS-CoV-2.

The research describes the neutralising strength, or potency, of each antibody and the likelihood it could offer protection against viral variants.

Antibodies with similar footprints on the spike are grouped into communities and the researchers show how antibodies from these different communities could be combined in antibody cocktails to target the virus.

"This map provides a reference to help predict which antibodies are still effective against SARS-CoV-2 variants of concern like the currently surging Delta variant," says Erica Ollmann Saphire, who leads the global Coronavirus Immunotherapeutic Consortium (CoVIC).

The researchers found three different groups of antibodies that are resistant to mutations in the SARS-CoV-2 spike protein and which could target vulnerable sites on the spike protein, even as it mutates. “We now have a framework for selecting durable antibody cocktails for COVID-19 treatment,” said Saphire.

CoVIC includes about 370 therapeutic antibodies from 59 different groups across academic labs and small biotechs, to large pharmaceutical companies.

The research provides a framework to understand, on a global scale, which antibodies are effective (or not) against which variants. This information will be key in ranking the pool of antibodies and deciding which to advance to further study.

All the data are freely accessible to other researchers looking to compare and contrast antibodies against the SARS-CoV-2 spike.  The combined information will help determine which antibodies would be candidates to move into clinical development.

Oxford Biomedica announced that Serum Life Sciences Ltd, a subsidiary company of Serum Institute of India, the world’s largest vaccines manufacturer, has agreed to invest just over £50 million to fund development of its COVID-19 vaccine manufacturing facility based Oxford.

The facility, called Oxbox, currently has three 1,000 litre bioreactors producing COVID-19 vaccine. The new investment will enable the rest of the facility to be developed, to increase production of vaccines and of viral vectors for use in gene therapy.

“Serum Institute of India has played a big part in the fight against COVID-19, as have we, and we look forward to a strong and collaborative relationship,” said John Dawson, CEO of Oxford Biomedica. “This investment will allow us to expand capacity at Oxbox at a time when our business development pipeline has never looked stronger.”

Oxford Biomedica’s commercial fortunes have been transformed by its agreement with AstraZeneca to manufacture the pharma’s COVID-19 vaccine. In May, it was announced that AstraZeneca was increasing the number of batches required from Oxford Biomedica in the second half of the 2021.

As a result, Oxford Biomedica increased its forecast for cumulative revenues from the contract to in excess of £100 million by the end of 2021.

In the first half of 2021, Oxford Biomedica’s revenue increased by 139% to £81.3 million, up from £34.0 million in the same period in 2020.

AstraZeneca has committed to supply its COVID-19 at cost during the current pandemic.

Pfizer and BioNTech announced plans to expand their agreement with the US government and to supply an additional 500 million doses of their COVID-19 vaccine at a not-for-profit price for donation to poor countries.

The expanded agreement brings the total number of doses to be supplied to the US government for donation to these countries to one billion.

The US will allocate doses of the Pfizer/BioNTech COVID-19 vaccine to 92 low- and lower-middle-income countries, and to the 55 member states of the African Union. Deliveries of the initial 500 million doses began in August 2021, and the total one billion doses under the expanded agreement are expected to be delivered by the end of September 2022.

The current plan is to produce these doses in Pfizer’s US facilities.

“In just nine months, Pfizer and BioNTech have delivered our COVID-19 vaccine to 130 countries and territories in every region of the world, and our expanded collaboration with the US will help us bring even more doses to those in need,” said Albert Bourla, CEO of Pfizer.

Ugur Sahin, CEO and co-founder of BioNTech said, “In the short term, we have pledged to deliver at least one billion doses this year and at least one billion doses next year to low- and middle-income countries. In parallel, we are exploring how to build a sustainable mRNA production infrastructure in low-income countries to democratise access to vaccines in the mid- and long-term. This applies to both individual production steps and complete manufacturing.”

To date, Pfizer and BioNTech have shipped more than 1.5 billion COVID-19 vaccine doses worldwide.

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