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

17 Jun 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.

While previous research has shown blood clotting is a significant cause of death in patients with COVID-19, it was not known why this happens.

Now, scientists have analysed blood samples from patients with COVID-19 treated in intensive care at a hospital in Dublin, finding the balance between a molecule that causes clotting, called von Willebrand Factor (VWF), and another molecule, ADAMTS13 that regulates it, are severely disrupted.

The discovery could lead to targeted therapies to prevent this from happening, the researchers say.

When compared to control groups, the blood of COVID-19 patients had higher levels of the pro-clotting VWF and lower levels of the anti-clotting ADAMTS13. Furthermore, the researchers identified other changes in proteins that caused the reduction of ADAMTS13.

"Our research helps provide insights into the mechanisms that cause severe blood clots in patients with COVID-19, which is critical to developing more effective treatments," said one of the researchers, Jamie O'Sullivan, of the Irish Centre for Vascular Biology in Dublin.

"While more research is needed to determine whether targets aimed at correcting the levels of ADAMTS13 and VWF may be a successful therapeutic intervention, it is important that we continue to develop therapies for patients with COVID-19,” O’Sullivan said. “COVID-19 vaccines will continue to be unavailable to many people throughout the world, and it is important that we provide effective treatments to them, and to those with breakthrough infections.”

The COVID-19 vaccine under development by German biotech CureVac is only 47% effective in preventing infections of the SARS-CoV-2 virus, according to an interim analysis of the phase III trial involving 40,000 volunteers.

The company said the failure to meet the pre-specified target for effectiveness was a result of a high number of variants of the virus circulating in the areas where the trial took place. While the vaccine, CVnCoV was designed against the original wild type of the virus that emerged in Wuhan, China, volunteers in the study were infected with a least 13 different variants.

A total of 57% of the infections were caused by the variants of concern, which have also been having an impact on the effectiveness of the approved vaccines.

Curevac said CVnCoV had a good safety profile and the trial will go through to the final analysis.

The interim analysis involved 134 cases of COVID-19 infection. Of these, the DNA of 124 viruses was sequenced and only one case was caused by the original Wuhan strain.

“We will continue the study,” said Franz-Werner Haas, CEO of Curevac. “The final efficacy may change.”  

With the World Health Organisation warning the Delta variant of the Sars-CoV-2 virus first detected in India is poised to take hold in Europe, there is positive news, indicating vaccines remain effective.

A new analysis by Public Health England (PHE) shows two doses of either Pfizer/BioNTech’s or Astrazeneca’s COVID-19 vaccines are preventing people infected with the Delta variant becoming seriously ill and needing to be admitted to hospital.

According to the date the Pfizer/BioNTech vaccine is 96% effective against hospitalisation after two doses, while the AstraZeneca vaccine is 92% effective against hospitalisation after two doses.

These are comparable with vaccine effectiveness against hospitalisation from the Alpha variant that first emerged in Kent in December and rapidly spread around Europe.

Further work remains underway to establish the level of protection the vaccines provide against mortality from the Delta variant.

The analysis included 14,019 cases of the Delta variant, 166 of whom were hospitalised, between 12 April and 4 June, looking at emergency hospital admissions in England.

PHE has previously published analysis showing that one dose is 17% less effective at preventing symptomatic illness from the Delta variant, compared to Alpha, underlining the importance of ensuring people are fully vaccinated.

A team of researchers at the Freiburg University Medical Centre has shown a severe inflammatory response can develop in the central nervous system of COVID-19 patients, involving different immune cells around the vascular system and in the brain tissue.

“Even though there was already evidence of central nervous system involvement in COVID-19, the extent of inflammation in the brain surprised us," said Henrike Salié co-author of the research published in the journal Immunity.

Notably, the researchers detected structures called microglial nodules that are not found in healthy brains. 

Using a novel measurement method, the researchers were able to image different cell types, including virus-infected cells, and to view spatial interactions of cells, in previously unseen detail.

"Until now, the inflammatory pattern in COVID-19 was poorly understood. Even compared to other inflammatory brain diseases, the inflammatory responses triggered by COVID-19 are unique and indicate a severe disturbance of the brain's immune response,” said Marco Prinz, medical director at the Institute of Neuropathology.

“In particular, the essential defence cells of the brain, microglial cells, are [very] strongly activated,” Prinz said. There was also pronounced neuroinflammation in the brain stem.

The immune changes are easiest to pick up in small blood vessels in the brain where the ACE2 receptor by which the virus enters human cells is expressed. Here, the virus was directly detectable. The researchers suggest that the immune system responds to these infected cells, sparking inflammation that then spreads to the nerve tissue, causing symptoms.

It is possible that early immunomodulatory or immunosuppressive treatment could reduce inflammation, they say.

After COVID-19 was officially declared a pandemic by the World Health Organisation (WHO), the peak in total number of clinical trials investigating therapies for the virus was 445, in April 2020.

There has since been a steady decrease in new clinical trials in every month, apart from December 2020 and March 2021, according to market research firm GlobalData.

There has been a divergence between therapies and vaccines, with the number of COVID-19 vaccines trials continuing to increase throughout the pandemic. The number peaked in March 2021 at 89 trials.

At the beginning of the pandemic there was a surge in trials of potential therapeutics in the scramble to find treatments for the infection. But once vaccines began to be approved, trials of therapies began to decline.

“The upward trend for vaccine COVID-19 clinical trials is expected to continue due to the same approved vaccines [being] tested against new variants of the virus,” said Scotty Chung-Siu, senior analyst at GlobalData. “On the other hand, the decrease in therapeutic COVID-19 clinical trials may be due to the increase in availability of vaccines, as well as the negative data in clinical trials from some therapeutics.”

The European Commission is making a push to expand access to COVID-19 vaccines in low and middle income incomes countries, whilst resisting the call to over-ride patents other countries, including the US, have called for.

In a speech to the European Parliament, setting out the position she will put to the G7 meeting taking place in the UK this coming weekend, Commission president Ursula von der Leyen said, “I want to be very clear: I think intellectual property has to be protected because it is the idea behind the breakthrough, and it retains the incentives for innovation in research and development.”

Rather than compulsory licensing, as called for by the World Trade Organisation (WTO), von der Leyen said voluntary licences are the most effective way to support local production of vaccines.

But she said, there is a “big however”. In a global emergency like this, “If voluntary licencing fails, compulsory licensing has to be, and is, the legitimate tool to scale up production,” von der Leyen said.

As von der Leyen noted, vaccine production requires not only patents but highly trained staff. “These are very complicated biological processes. They require know-how, they require technology, they require skilled personnel and, of course, infrastructure,” she said.

Simply waiving intellectual property rights will not increase production. “It is actually by collaboration and, if need be, compulsory licensing that you enhance technology transfer,” von der Leyen said.

But patents should not stand in the way, which is why Europe had started an initiative in WTO to simplify compulsory licensing, said von der Leyen.

In addition, the EU has committed €1 billion to help set up vaccine manufacturing hubs in Africa. The G7 meeting will provide a good opportunity to reaffirm the EU’s commitments “and to go even further,” von der Leyen said. 

G7 health ministers committed to a new international agreement designed to make it easier and quicker to share results from vaccine and therapeutic trials to tackle COVID-19 and prevent future health threats.

The Therapeutics and Vaccines Clinical Trials charter will help deliver high quality, reliable and comparable evidence from international clinical trials, to speed up access to approved treatments and vaccines.

During the COVID-19 pandemic some of the rapidly organised clinical trials played a critical role in informing public health and clinical decisions, but many other studies were inadequate in size, design and how they were conducted, failing to generate reliable evidence.

More effective international collaboration on trials would have made better use of scarce resources and may have saved lives. An assessment by the US Food and Drug Administration suggests only about a quarter of enrolled patients contributed to adequately powered and well controlled trials.

While vaccine development has been faster in the pandemic than ever before, improvements can be made. For example, the use of different laboratory testing methods and reagents meant it was often not possible to compare immune responses directly; a lack of pre-agreed processes was a barrier to the cross-border movement of materials; and there was no overall coordination of trial testing methodology.

The G7 charter pledges to avoid the proliferation of trials that do not contribute valid evidence, prioritising support for randomised controlled trials. This will be taken this forward through national healthcare and research systems, with ministers agreeing to promote communication and coordination between them.

To avoid unnecessary duplication in future the G7 will coordinate emergency and preparedness research agendas, for example, sharing vaccines and therapeutics national research agendas and sharing information on ongoing and planned trials.

A team led by researchers at Newcastle University has demonstrated that the gene HLA-DR1 is found three times more often in people who have a confirmed COVID-19 infection but don’t have any symptoms, suggesting the gene confers some level of protection from severe infection.

HLA-DR1 is known to be involved in the body’s immune response to infections and the researchers believe this is the first clear evidence of inbuilt genetic resistance to the worst effects of COVID-19.

Carlos Echevarria from the Translational and Clinical Research Institute at Newcastle University who is a respiratory consultant at Newcastle Hospital said, "This is an important finding as it may explain why some people catch COVID but don't get sick.”

It could lead to a genetic test to help in prioritising those most at risk when designing vaccination programmes. Knowing who has this natural genetic resistance would also be important for other control measures.

"At a population level, this is important for us to know because when we have lots of people who are resistant, so they catch COVID but don't show symptoms, then they risk spreading the virus while asymptomatic," Echevarria said.

The study used samples from 49 patients with severe COVID-19 who had been hospitalised with respiratory failure, samples from an asymptomatic group of 69 hospital workers who had tested positive, and a historic control group.

Daily crime counts before and after COVID-19 restrictions were implemented in major metropolitan areas such as Barcelona and London show that while stringency of lockdowns varied considerably from city to city, most types of crime fell significantly.

Overall, stricter lockdowns led to greater declines in crime, but even cities with voluntary "recommendations" instead of restrictions, such as Malmo and Stockholm in Sweden, saw drops in daily rates of theft, according to the study led by researchers at the universities of Cambridge and Utrecht.

Across 27 cities worldwide, daily assaults fell by an average of 35%, robberies involving violence or intimidation almost halved, falling an average of 46%, and other types of theft, from pick pocketing to shoplifting, fell an average of 47%.

Theft of vehicles fell by an average of 39% over the study sites. Researchers found that tougher restrictions on use of buses and trains during lockdowns was linked to greater falls in vehicle theft - suggesting that negotiating cities via public transport is often a prerequisite for stealing a car.

In Barcelona there were massive falls in the number of assaults (84% drop) and robberies (80% drop). Thefts reported to police in the city declined from an average of 385 per day, to just 38 per day under lockdown.

London saw less pronounced, but still significant falls in some crime, with daily robberies dropping by 60%, theft by 44% and burglaries by 29%.

"City living has been dramatically curtailed by COVID-19, and crime is a big part of city life," said Manuel Eisner, director of the Violence Research Centre at Cambridge University, who is senior author of the study published in Nature Human Behaviour.

"No drinkers spilling into the streets after nights out at bars and pubs. No days spent in shops and cafés, or at the racetrack or football match. Some cities even introduced curfews. It choked the opportunism that fuels so much urban crime,” said Eisner.

The one exception was the number of murders committed, with a fall of just 14% on average across all cities in the study. Criminologist Amy Nivette, assistant professor at Utrecht University said, "In many societies, a significant proportion of murders are committed in the home. The restrictions on urban mobility may have little effect on domestic murders.”

Falls in crime resulting from COVID-19 stay-at-home orders tended to be sharp but short-lived, with a maximum drop occurring around two to five weeks after implementation, followed by a gradual return to previous levels.

"The measures taken by governments across the world to control COVID-19 provided a series of natural experiments, with major changes in routines, daily encounters and use of public space over entire populations,” Eisner said. "The pandemic has been devastating, but there are also opportunities to better understand social processes, including those involved in causing city-wide crime levels."

The largest analysis to date shows that unnecessary use of antibiotics to treat patients with serious COVID-19 could be fuelling bacterial resistance.

The research found that antibiotic use was very high in hospitalised COVID-19 patients in the UK during the first wave of the pandemic, despite confirmed bacterial infections being uncommon.

Of 46,000 patients in the study, 85% received one or more antibiotics when in hospital, while 37% of patients were prescribed antibiotics prior to admission. In the event, only 1,017 of the patients had a confirmed bacterial infection.

The researchers believe the high level of antibiotic use in the UK is likely to be replicated elsewhere, meaning the COVID-19 pandemic could undermine international efforts to preserve the effectiveness of antimicrobial drugs.

The overuse of antibiotics during the first wave, in February to May 2020, is attributed to the fact that there was little knowledge of COVID-19 and how to treat it. Other viral respiratory infections, notably influenza, are strongly associated with bacterial co-infections, leading clinicians to treat COVID-19 patients with antibiotics on a just-in-case basis.

Currently, national and international COVID-19 guidelines vary in their recommendations on such empirical antibiotic use. UK guidelines have now been updated to advise against antibiotics in COVID-19, without specific evidence of bacterial infection.

In the UK study, very few patients had bacterial co-infections when first admitted to hospital, and the few infections that did occur began more than 48 hours after admission.

These secondary infections were not specific to COVID-19, but more in keeping with the usual run of hospital-acquired infections, particularly those typically seen in intensive care units.

“Until now, a detailed understanding of the nature of bacterial co-infections identified in patients with COVID-19, and the frequency and types of antibiotics these patients have been prescribed has been lacking,” said Antonia Ho of Glasgow University’s Centre for Virus Research, who led the study.

“This study demonstrates the very high antibiotic use we see in hospitalised COVID-19 patients may not be necessary, indeed it may contribute to antimicrobial resistance,” she said

Some COVID-19 patients will require antibiotics, mostly for secondary infections which develop after admission to hospital, but not all COVID-19 patients should be prescribed antibiotics. “The bugs we identified are similar to those found in patients with hospital-acquired infection, and not specific to COVID-19,” Ho said.

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