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

13 Jan 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 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.

Johnson & Johnson announced new data showing that protection against COVID-19 increases when a booster shot of its vaccine is administered, with the safety profile remaining consistent and the vaccine generally well-tolerated when administered as a booster.

“Our large real world evidence and phase III studies confirm that the single shot Johnson & Johnson vaccine provides strong and long lasting protection against COVID-19-related hospitalisations. Additionally, our phase III trial data further confirm protection against COVID-19-related death,” said Mathai Mammen, global head of research & development, Johnson & Johnson.

“It is critical to prioritise protecting as many people as possible against hospitalisation and death given the continued spread of COVID-19,” said Paul Stoffels, chief scientific officer. “A single shot COVID-19 vaccine that is easy to use, distribute and administer, and that provides strong and long lasting protection is crucial to vaccinating the global population. At the same time, we now have generated evidence that a booster shot further increases protection against COVID-19 and is expected to extend the duration of protection significantly.”

In what it says is the largest real world evidence study for a COVID-19 vaccine reported to date in the US, the vaccine was 81% effective in preventing COVID-19-related hospital admissions. There was no evidence of reduced effectiveness over the study duration, including when the Delta variant became dominant in the US.

The study included 390,000 people who received the Johnson & Johnson COVID-19 vaccine and approximately 1.52 million matched unvaccinated people.

When a booster of the Johnson & Johnson COVID-19 vaccine was given two months after the first dose, antibody levels rose to four to six times higher than seen after the single shot.

When a booster of the Johnson & Johnson COVID-19 vaccine was given six months after the single shot, antibody levels increased nine-fold one week after the booster, and continued to climb to 12-fold higher four weeks after the booster. All rises were irrespective of age.

Researchers in the UK have used population level databases to develop an algorithm that can predict individuals who are at risk of hospitalisation and death if they contract COVID-19, despite being fully vaccinated.

The QCovid tool is based on data from 6.9 million vaccinated individuals, of whom 5.2 million had received two doses, a cohort that is representative of the UK population as a whole. Health databases are linked, meaning each person could be followed up via their general practitioner records, by referring to COVID-19 testing results and through hospital admission and death records.

Vaccines are providing a high level of protection but a small number of people are still experiencing serious illness if they get COVID-19, with age remaining by far the greatest risk factor. Also remaining at risk are those whose immune systems are compromised as a result of chemotherapy, because they are taking immune-supressing medicines following a solid organ transplant, or who have HIV/AIDS.

Applying the algorithm to UK data on hospital admissions and deaths showed some groups that were classified as being at high risk before vaccination, are no longer at higher risk of hospitalisation and death once they have been vaccinated. That includes ethnic minorities, apart from those of Indian or Pakistani heritage.

The risks identified by the algorithm have been validated against separate datasets, showing what the researchers say is “excellent ability” to identify those at highest risk of death and “very good” ability to identify who will need hospital care. The research was published in the British Medical Journal.

The tool can be used to identify those who would benefit from booster doses of vaccine or to decide who should receive new treatments, such as expensive antibody drugs, that help the body to fight infections.

Reporting the first results of a pivotal trial of any COVID-19 vaccine in children under 12 years of age, Pfizer and German biotech BioNTech said their mRNA vaccine was safe, well tolerated and showed robust neutralising antibody responses in children age 5 – 11.

The companies said they will submit the data to the European Medicines Agency, the US Food and Drug Administration and other drug regulators as soon as possible.

The trial used two doses of 10 micrograms administered 21 days apart. While that is a smaller dose than the 30 microgram dose used for people 12 and older, the antibody responses were comparable.

“We are eager to extend the protection afforded by the vaccine to this younger population, subject to regulatory authorisation, especially as we track the spread of the Delta variant and the substantial threat it poses to children,” said Albert Bourla, CEO of Pfizer.

Since July, cases of COVID-19 in children have risen by about 240% in the US, Bourla noted. “These trial results provide a strong foundation for seeking authorisation of our vaccine for children 5 to 11 years old.”

The data was for 2,268 participants who were 5 to 11 years of age. Top line readouts for the other two age cohorts from the trial, of children 2 - 5 years of age and children 6 months to 2 years of age, are expected before the end of the year.

A request to the EMA to update the EU conditional marketing authorisation is now planned.

US biotech Gritstone Bio announced the first volunteer has been dosed in a phase I trial evaluating the ability of its second generation mRNA COVID-19 vaccine, GRT-R910, to boost and expand the immunogenicity of first generation COVID-19 vaccines in people aged 60 years or older. The single centre study is being conducted by Manchester University and its associated teaching hospital.

GRT-R910 uses lipid nanoparticles to deliver a broad set of antigens against SARS-CoV-2, including both stabilised spike protein and highly conserved regions of the virus viral protein. Gritstone says the self-amplifying properties and extended duration and magnitude of antigen production may make it possible to lower vaccine doses, or eliminate the need for repeat administration, and has potential to elicit immune responses across SARS-CoV-2 variants.

“Since viral surface proteins like the spike protein are evolving and sometimes partially evading vaccine-induced immunity, we designed GRT-R910 to have broad therapeutic potential against a wide array of SARS-CoV-2 variants, by also delivering highly conserved viral proteins,” said Andrew Allen, CEO of Gritstone.

The Gritstone trial, which is initially expected to enrol 20 volunteers, will explore the ability of GRT-R910 to boost and expand the immunogenicity of AstraZeneca's first-generation COVID-19 vaccine in healthy adults over 60 years of age.

“The observed waning of vaccine-elicited immune responses, particularly in older individuals, coupled with the prevalence of emerging variants, highlights the need for continued vigilance to keep COVID-19 at bay,” said Andrew Ustianowski, consultant in infectious diseases and tropical medicine at North Manchester General Hospital, who is lead investigator. “Using GRT-R910 as a boost vaccination is expected to elicit strong, durable, and broad immune responses, which are likely critical to maintaining protection in this vulnerable elderly population with increased mortality risk.” Ustianowski said.

With more than 70 per cent of adults in the EU fully vaccinated against COVID-19, the next and most urgent priority is to speed up global vaccination, Commission president Ursula von der Leyen said in the annual state of the union address.

“With less than 1% of global doses administered in low-income countries, the scale of injustice and the level of urgency are obvious. This is one of the great geopolitical issues of our time,” said von der Leyen.

The EU is investing €1 billion to ramp up mRNA production capacity in Africa and has so far committed to share 250 million doses. The Commission will add a new donation of another 200 million doses by the middle of next year.

At the same time, the EU will continue its efforts in Europe, aiming to address the “worrisome divergences” in vaccination rates between member states. “Let's do everything possible to ensure that this does not turn into a pandemic of the unvaccinated,” said von der Leyen.

The EU has an additional 1.8 billion doses of COVID-19 vaccines on hand and ready to use when booster shots are needed.

The final priority is to strengthen preparedness for future pandemics by setting up the European Health Union.  This will be backed by a new health preparedness and resilience research mission covering the whole of the EU, and backed by investment of €50 billion by 2027.

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