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

Low-income countries would add $38 billion to their GDP forecast for 2021 if they had the same COVID-19 vaccination rates as high-income countries, according to new data released today by the United Nations Development Programme, the World Health Organisation (WHO) and Oxford University.

As a result, global economic recovery is at risk if vaccines are not equitably manufactured, scaled up and distributed, with COVID-19 vaccine inequity having a lasting impact on socio-economic recovery in poorer countries.

The new COVID-19 Vaccine Equity Dashboard, combines the latest information on COVID-19 vaccination with the most recent socio-economic data, to illustrate why accelerating vaccine equity is not only critical to saving lives but also to driving a faster and fairer recovery with benefits for all.

“In some low- and middle-income countries, less than 1% of the population is vaccinated – this is contributing to a two-track recovery from the COVID-19 pandemic”, said Achim Steiner of the UN development programme.

“Vaccine inequity is the world’s biggest obstacle to ending this pandemic and recovering from COVID-19,” said Tedros Adhanom Ghebreyesus, director general of the World Health Organisation.

The Global Dashboard breaks down the impact of accessibility against a target for countries to vaccinate their at-risk populations, first to reduce mortality and protect the health system, and then move on to vaccinating larger shares of the population to reduce disease burden and re-open socio-economic activity.

Since the beginning of the pandemic, several reports have indicated that SARS-CoV-2 has been transmitted from humans to animals, as evidenced by the transmission of the virus between keepers and tigers and lions in the Bronx Zoo in New York.

However, to date the full range of animal species that are susceptible to the viral infection remains unclear. Conventionally, that would be assessed experimentally by infecting a large variety of animal species with SARS-CoV-2, but researchers at the University of Bern have used their knowledge of in vitro cell culture models of the human respiratory tract to create a large collection of cell models from various domesticated and wild animals.

This will be an important resource in controlling the pandemic. "This will benefit the general public since it will help prevent new SARS-CoV-2 variants from developing in animal reservoirs and potentially being reintroduced into the human population, to which the current vaccines may not be protective," said Ronald Dijkman, from the Institute for Infectious Diseases at the University of Bern.

Currently, Swiss research funding from the EU is under threat. The work on the test tube zoo was supported by the European Commission’s Marie Sklodowska-Curie Innovative Training Network, with the Swiss National Science Foundation, the German Federal Ministry of Education and Research, and the Swiss Federal Food Safety and Veterinary Office.

The team isolated airway epithelial cells from tissue from deceased animals and created a cell biobank from different animal species that can be used to determine whether these animals can be infected with SARS-CoV-2.

No live animal experiments were involved. To date, the cell biobank contains primary cells from a rhesus macaque, cat, ferret, dog, rabbit, pig, cattle, goat, llama, camel, and two bat species.

"Our collection is unique, and thus far we are the first that have used such a large collection of advanced in vitro cell culture models from various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2 infection,” Dijkman said.

The researchers found their in vitro results agree well with previously published studies using live animals to assess susceptibility to SARS-CoV-2 infection. For example, the researchers observed that SARS-CoV-2 replicated in the cell models of monkey and cats, without the need for the virus to adapt.

"Our findings, together with the reports from previously documented spillover events, indicate that close surveillance of these animals and other close relatives, whether they live in the wild, captivity or households, is necessary,” said Dijkman.

Testing of an entire Italian town shows antibody levels remain high nine months after SARS-CoV-2 infection, whether symptomatic or asymptomatic, according to researchers from the University of Padua and Imperial College London.

They tested more than 85% of the 3,000 residents of Vo', Italy, in February - March 2020 for infection with SARS-CoV-2, the virus that causes COVID-19, and then tested them again in May and November 2020 for antibodies against the virus.

The team found that 98.8% of people infected in February - March showed detectable levels of antibodies in November. There was no difference between people who had suffered symptoms of COVID-19 and those that had been symptom-free. The results are published in the journal Nature Communications.

Antibody levels were tracked using three assays that each detected different antibodies generated in response to different parts of the virus. While all antibody types showed some decline between May and November, the rate of decay differed.

The team also found cases of antibody levels increasing in some people, suggesting potential re-infections with the virus, providing a boost to the immune system.

Ilaria Dorigatti, from the MRC Centre for Global Infectious Disease Analysis at Imperial College, said, "We found no evidence that antibody levels between symptomatic and asymptomatic infections differ significantly, suggesting that the strength of the immune response does not depend on the symptoms and the severity of the infection.”

However, the study does shows that antibody levels vary. This means that caution is needed when comparing estimates of infection levels in a population obtained in different parts of the world with different tests and at different times.

Testing in May showed 3.5% of the Vo' population had been exposed to the virus, even though not all of these subjects were aware of their exposure, given the large fraction of asymptomatic infections.

The team also investigated the infection status of household members, to estimate how likely an infected member is to pass on the infection within the household. Their modelling suggests that there was a probability of about 1 in 4 that a person infected with SARS-CoV-2 passes the infection to a family member and that 79% of transmission is caused by 20% of infections.

This confirms that there are large differences in the number of secondary cases generated by infected people. The large differences in how one infected person may infect others in the population suggest that behavioural factors are key for epidemic control. Physical distancing, as well as limiting the number of contacts and mask wearing, continue to be important to reduce the risk of transmitting the disease, even in highly vaccinated populations.

Teasing apart the impact of various control measures, the researchers showed that, in the absence of case isolation and short lockdowns, manual contact tracing alone would not have been enough to suppress the epidemic.

Spanish researchers have shown a blood test that quantifies ACE2, the cellular protein which allows the SARS-CoV-2 virus to enter human cells, and ACE2 fragments produced as a result of interaction with the virus, could be an effective method for monitoring SARS-CoV-2 infection.

In a study carried out during the first wave of the pandemic, patients with COVID-19 who were in the acute phase of infection had significantly reduced blood levels of the full-length ACE2 protein, while levels of an ACE2 fragment, generated as a result of interaction with the virus, increased.

The abnormal levels of ACE2 and truncated ACE2 returned to normal after the patients recovered, suggesting these two forms of ACE2 could be used as a biomarker of the evolution of coronavirus infection. In addition, truncated ACE2 levels made it possible to distinguish between patients infected with SARS-CoV-2 and those with flu, the researchers say.

The latest assessment of the COVID-19 situation in the EU by the European Medicines Agency (EMA) and the European Centres for Disease Control (ECDC) shows the Delta variant (B.1.617.2), first identified in India, is spreading fast in Europe and may “seriously hamper” efforts to control the pandemic.

The evidence suggests Delta is 40% to 60% more transmissible than the earlier Alpha (Β.1.1.7) variant first identified in Kent, which drove the second wave of infection from December to May, and which was the first major variant of concern in the EU.

In addition, the Delta variant may be associated with higher risk of hospital admission, EMA and ECDC said in a joint update.

ECDC estimates that by the end of August the Delta variant will represent 90% of all SARS-CoV-2 viruses circulating in the EU.

Taken together, this makes it essential for countries to speed up vaccination programmes, including second doses, to prevent new infections and reduce the possibility of the further emergence of variants, the update says.

The risk of severe disease and mortality caused by COVID-19 is greater for older age groups and those with other underlying conditions. However, there are still 10 EU/EEA countries where nearly 30% or more of individuals older than 80 years have not yet completed the recommended vaccination course, according to ECDC’s Vaccine Tracker.

Further effort is also needed in some countries to increase vaccine uptake among health and social care workers.

The use of two different vaccines may allow populations to be protected more quickly and make better use of available vaccine supplies, but currently EMA and ECDC say they are not in a position to make any definitive recommendations on use of different COVID-19 vaccines for the two doses.

It’s also too early to confirm if and when a booster dose for COVID-19 vaccines will be needed.

Other measures such as mask wearing and social distancing will need to be maintained at a level sufficient to contain community transmission of the Delta variant until more of the populations are fully vaccinated, EMA and ECDC say.

ReiThera has published preliminary safety and immunogenicity data from the phase II clinical of GAd-COV2, its novel COVID-19 vaccine, showing it was well tolerated after the first, and even better after the second dose.

Antibody responses against the SARS-CoV-2 spike protein were achieved in over 93% of the volunteers at three weeks after the first dose, reaching 99% after the second dose. Five weeks after the first vaccination, levels of spike-binding and SARS-CoV-2 neutralising antibodies were comparable to that measured in a reference group of patients recovering from COVID-19 infection.

The study, conducted in 24 clinical centres in Italy, enrolled 917 volunteers over the age of 18, of whom 25% were over the age of 65 and/or had conditions associated with an increased risk of severe disease in case of SARS-CoV-2 infection. Volunteers were randomised to receive either a single vaccine dose followed by a placebo dose, or two vaccine doses, or two doses of placebo, with a three week interval between the two administrations.

“We are very excited about the preliminary phase II data,” said Roberto Camerini, Reithera’s medical director. “Our vaccine candidate confirmed its excellent safety and good immunogenicity profile in a large cohort.”

The phase III programme has approval from the European Medicines Agency and other regulatory agencies, and will start as soon as possible, Camerini said. 

Today and tomorrow, the Commission is hosting a pan-European matchmaking event to accelerate and scale up development and manufacturing of COVID-19 therapeutics in the EU, bringing together over 250 participants from across the value chain in 25 member states and other countries.

The event aims to increase the participation of companies in EU value chains for COVID-19 therapies, speed up connections between organisations and companies, and help in production planning.

It was kicked off by opening speeches by commissioners Thierry Breton and Stella Kyriakides.

“The EU is making good progress on vaccination, with 50% of adults now fully vaccinated. But vaccines are not our only response to COVID-19,” Kyriakides said. With the spread of variants and the resurgence of cases across the EU in recent weeks, the development of therapeutics is more necessary than ever. “I am encouraging companies to step forward and join forces to develop and produce COVID-19 therapeutics in the EU,” said Kyriakides.

The EU therapeutics strategy has identified five COVID-19 treatments and has set the target that three new drugs to treat the infection are approved by October 2021.

Breton, who is responsible for the internal market, said Europe has now produced and delivered enough doses of vaccine to vaccinate 70% of the adult population, becoming the world's biggest producer of mRNA vaccines. “This would not have been possible without new partnerships across the industrial ecosystem. We now want to forge new collaborations to ensure that Europe also leads the way in developing new life-saving COVID-19 treatments,” he said. 

The response of the UK life sciences sector to COVID-19 will be used as a blueprint to accelerate development of drugs and devices for other diseases, as part of a ten year life sciences strategy published on Wednesday.

The strategy, co-developed with companies and experts in the field, outlines seven healthcare missions on which the government, industry, the National Health Service, academia and medical research charities will work together.

The missions will focus on preventing, diagnosing, monitoring and treating disease early, using novel clinical trial designs to develop products and treatments quickly, and ensuring rapid adoption of drugs, diagnostics, medical technology and digital tools.

In particular, the strategy looks to emulate the successes of the UK Vaccines Taskforce in harnessing private sector expertise and removing unnecessary bureaucracy so that  healthcare challenges set out in the missions can be tackled at speed and at risk.

Amongst other objectives, the missions aim to accelerating the pace of studies into novel dementia treatments; sustain the UK’s position in vaccine discovery, development and manufacturing; promote development of treatments for cardiovascular diseases; reduce mortality and morbidity from respiratory diseases; and address the underlying biology of ageing.

Prime minister Boris Johnson said the seamless collaboration between scientists, industry, regulators and the NHS during the pandemic should become “the norm”.

Business minister Kwasi Kwarteng said the strategy sets out how to replicate the scientific excellence and agility seen in dealing with the pandemic in other health challenges, and “doing with cancer, dementia and obesity what we did with this virus – gaining the upper hand with brilliant science.”

To support the strategy, the government launched a Life Sciences Investment programme, with £200 million for venture capital firms to invest in growth companies. In addition, the government has a commitment from the Abu Dhabi sovereign wealth fund, the Mubadala Investment Company, to invest £800 million in the UK life sciences industry.

A new modeling study suggests that significant variation in virus dynamics from person to person may be contributing to the inconsistent findings of clinical trials of COVID-19 antiviral drugs.

Recruiting trial participants shortly after symptoms begin could reduce the number needed to detect antiviral drug effects, according a study by US and Japanese researchers.

The conclusions are based on a model of the dynamics of the SARS-CoV-2 virus that causes COVID-19, once it has infected an individual. They combined the model with clinical data to examine how viral load in a person’s throat changes over time, and found significant variation in the rate of decline. These differences may contribute to the inconsistent results reported in non-randomised clinical trials so far, they say.

The researchers then simulated potential findings of randomised clinical trials for COVID-19 drugs that successfully interrupt virus replication. They found that, even a drug that that was so effective it reduced viral replication by 95%, a randomised clinical trial would need to enrol more than 26,000 people to detect statistically significant differences in viral load.

But when the researchers adjusted the simulated trials so participants were treated within one day of onset of their symptoms, only 1,200 participants were needed. They say future studies could employ more detailed models of SARS-CoV-2 dynamics, enabling better predictions of how many participants are needed to produce meaningful results.

Only 4% of studies investigating treatments for COVID-19 registered on the US site ClinicalTrials.gov explicitly report a plan to include sex and/or gender as an analytical variable.

This is despite the fact that sex and gender differences impact the incidence of SARS-CoV-2 infection and COVID-19 mortality. According to the researchers, the inclusion of sex as a variable could aid in the identification of effective interventions and provide insights into COVID-19 pathology.

Gender, as a socially constructed variable that can describe identity, norms and relations between individuals, can affect access to testing, diagnosis, medical care and treatments and also influences the availability of social, economic and logistical support.

Excluding sex differences in reporting results of clinical trials could lead to an increase in the risk of side effects for the excluded sex, while not addressing gender as a variable misses an opportunity to address healthcare inequality, say Sabine Oertelt-Prigione and colleagues, in research published in the journal Nature Communications.

They analysed the inclusion of sex and gender in COVID-19 studies registered on ClinicalTrials.gov (which in general includes all trials running in Europe and elsewhere, as well as the US) between 1 January 2020 and 26 January 2021. They identified 237 studies that planned sex-matched or representative samples, or emphasised sex and/or gender reporting, and 178 studies that reported a plan to include sex and/or gender as an analytical variable.

However, that was a drop in the ocean of 4,420 studies registered, the majority of which - 2,496 studies - did not refer to sex or gender, and 935 studies which mentioned sex or gender solely in the context of recruitment.

The researchers argue everyone working in COVID-19 and SARS-CoV-2 research should implement a sex-specific methodology and more comprehensive analysis, addressing gender-related impacts.