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

New WHO/Europe guidance published today urges countries to urgently address gaps in pandemic monitoring and response to avoid preventable deaths and severe disruption to healthcare systems.

Hans Kluge, WHO Regional Director for Europe says it is now “abundantly clear” Europe is in a similar situation to last summer, when COVID-19 infections were on the rise. The latest wave is being propelled by sub-lineages of the Omicron variant, notably BA.2 and BA.5, with each dominant sub-lineage of Omicron showing clear transmission advantages over the previously circulating viruses.

The European Region has seen a tripling of new COVID-19 cases over the past 6 weeks, with close to three million new cases reported last week, accounting for nearly half of all new cases globally. While hospitalisation rates due to COVID-19 have doubled in the same period, intensive care unit admissions have so far remained relatively low.

However, as infection rates in older groups continue to rise, Europe is still seeing close to 3,000 people die of COVID-19 every week.

 “With rising cases, we’re also seeing a rise in hospitalisations, which are only set to increase further in the autumn and winter months as schools reopen, people return from holidays and social mixing moves indoors with the onset of colder weather. This forecast presents a huge challenge to the health workforce in country after country, already under enormous pressure from dealing with unrelenting crises since 2020,” Kluge said. 

WHO/Europe is released its autumn/winter strategy for COVID-19 and other respiratory viruses to help prepare for the coming waves of infection. “Waiting for the autumn to act will be too late,” said Kluge. 

The strategy calls on countries to relaunch mitigation efforts and be ready to respond to an increased burden on their healthcare systems.

“More than two years into the pandemic, we’re all aware of the tools we have to keep ourselves safe, assess our level of risk and take the necessary steps to protect others if we get infected,” Kluge said.

As with coughing, sneezing, talking and singing, playing wind instruments ­– particularly those in the brass section – can spread respiratory particles that may carry the SARs-CoV-2 virus.

Early in the pandemic, engineers at Colorado State University, led by John Volckens teamed up with musicians to try and quantify respiratory particle emissions from music-playing.

The researchers used an aerosol measurement chamber and recruited volunteers to perform in the chamber while aerosol emissions from the musicians and their instruments were analysed. The 81 volunteers played wind instruments including the bassoon, clarinet, French horn, oboe, piccolo, saxophone, trombone, trumpet and tuba.

Brass instruments on average, produced 191% more aerosols than woodwinds. The researchers’ highest particle counts of brass playing were even higher than their highest results from singers in a previous study, by nearly a factor of four.

Being male was also associated with a 70% increase in emissions from instrument-playing, probably due to lung size and capacity. Louder playing of brass instruments was associated with higher particle counts, but louder playing of woodwinds did not increase emissions.

The researchers also took measurements with performers using bell covers in an attempt to mitigate the particle spread, which seemed to work. The use of the covers reduced emissions from trombone, tuba and trumpet players by an average of 53-73%, but not from the oboe or clarinet.

Volckens, a mechanical engineer and aerosols expert, likened bell covers to blue surgical masks for instruments ­– good, but not great in terms of limiting spread.

“The data suggest that masks and bell covers cut down half to 75% of particles coming out of the mouth or instrument,” Volckens said. “And the reason blue surgical masks or bell covers don’t work better is that they’re just not a tight fit.”

The researchers say this study, and previous ones like it, confirm that the start of the pandemic, particularly before the advent of vaccines, shutting down performing arts in the name of safety is likely to have saved lives.

An expert review of data from 79 real-world studies has shown that AstraZeneca’s COVID-19 vaccine, Vaxzevria, provides equally effective protection against hospitalisation and death from COVID-19 following two doses, as do the mRNA vaccines that have dominated vaccination programmes in Europe.

Data on vaccine use and impact, collated by Johns Hopkins University and the International Vaccine Access Centre, was reviewed by infectious disease experts from across Asia. The study findings are published in Expert Review of Vaccines.

The analysis shows Vaxzevria and Pfizer/BioNTech and Moderna’s COVID-19 vaccines offer an equivalent degree of protection against hospitalisation (91-93%) and death (91-93%), regardless of age.

The data available at the time of review relates to the Delta SARS-Cov-2 and earlier variants. However, emerging data on third dose boosting from the UK Health Security Agency and Brazil  indicate similar findings on serious COVID-19 outcomes resulting from the Omicron variant that is currently rife.

Guy Thwaites, director of the Oxford Clinical Research Unit in Vietnam and one of the study’s authors, said, “Our expert review shows that Vaxzevria and available mRNA vaccines provide similar, high-level protection against life-threatening COVID-19. This is important information for policymakers as they consider the optimal deployment of COVID-19 vaccines in their populations over the next 12 months.”

John Perez, senior vice president, head of th late development vaccines unit, AstraZeneca said, “We are pleased that these data continue to show high-levels of protection against severe clinical outcomes and further our understanding of the important role that vaccination plays in the containment of COVID-19.”

While it started out level pegging with the mRNA vaccines, the popularity of Vaxzevria plummeted after reports of adverse events showed that unusual blood clots with low blood platelets are a rare side effect. The European Medicines Agency said a warning to that effect should be added to the label.

The Johns Hopkins database is updated on a weekly basis to include global real-world studies on vaccine effectiveness, but it is not currently designed to capture the safety outcomes of these studies, preventing safety comparisons between different types of vaccines.

Unlike Pfizer/BioNTech and Moderna, AstraZeneca widely licensed the Vaxzevria intellectual property and transferred the manufacturing knowhow to manufacturers around the world in low an from the very early days of development getting underway. The company’s partners have released over three billion vaccine doses to more than 180 countries, and approximately two thirds of these doses have been delivered to low and lower-middle income countries.

Based on modelling of outcomes, Vaxzevria is estimated to have helped save over six million lives between 08 December 2020 and 08 December 2021.

Researchers at the University of Zurich (UZH) who have studied whether infants born during the pandemic exhibit different social behaviour from same-aged infants before the pandemic, conclude they do not seem to be developing any differently.

They reached this conclusion by assessing the children’s ability to follow another person’s gaze.

“This ability is fundamental for engaging in social interactions, building relationships and developing language skills,” said Stephanie Wermelinger, who researches developmental psychology in infants and children in the department of psychology at UZH. If this ability is impaired, it can hamper a person’s ability to interact with society, as is the case for people with autism.

Eighty infants between the age of 12 and 15 months took part in the study. They were shown different videos in which a person was gazing at one of two objects. By tracking the infants’ eye movements, the researchers recorded how often and how quickly the infants followed the person’s gaze. They then compared their data with eye movement data from 133 children using the same method before the pandemic.

There were no significant behavioural differences between the children born during and before the pandemic. Children born during the pandemic followed the person’s gaze just as often and quickly as the children in the pre-pandemic group.

That is despite the pandemic meaning the children in the study saw fewer people overall and interacted with more people who were wearing masks. They do not seem to be developing any differently from children who didn’t experience those pandemic-related changes, the researchers say.

“We believe the unchanged social interactions with parents and caregivers at home are enough to mitigate any influence the COVID-19 pandemic might have had on infants,” Wermelinger said.

Moderna has announced its bivalent vaccine mRNA-1273.214, which is designed against both the original Wuhan strain of SARS-CoV-2 and the Omicron variant, has demonstrated significantly higher antibody titers against all tested variants of the virus, including Omicron BA.1 and the BA.4 and BA.5 subvariants, and their forerunners, Alpha, Beta, Delta, and Gamma.

The company has filed for approval in Europe and said it expects to complete most filings elsewhere this week.

One month after administration in previously vaccinated and boosted participants, a booster dose of mRNA-1273.214 elicited significantly higher levels of neutralising antibody responses against the Omicron subvariants BA.4, and BA.5 which currently is causing a new wave of infections in Europe, compared to Moderna’s original vaccine. The effect was seen regardless of prior infection status or age.

This latest update adds to the largest body of data confirming the superiority of a bivalent approach, said Stephane Bancel, CEO of Moderna. “This superior breadth and durability of immune response following a bivalent booster has now been shown in multiple Phase II/III studies involving thousands of participants," he said.

The mRNA-1273.214 bivalent booster is the only modified COVID-19 vaccine expected to have demonstrated significantly higher titres against Omicron BA.4 and BA.5 in a clinical trial before the autumn booster season.

“It was always a given that the first generation of these vaccines would require modifications, however, unfortunately we are always a step behind the virus evolution,” said Beate Kampmann, director of the Vaccine Centre at the London School of Hygiene and Tropical Medicine, reacting to the Moderna data. “Unfortunately we are always a step behind the virus evolution.  We ultimately need to get to a space where models might predict what happens next, so we can get ahead of the curve.”

The question of who needs a booster is a bit of a moving target too. “We are now facing a mix of community immunity and personal protection induced by vaccines or natural infection - and most likely both. In the absence of a personalised vaccination approach, able to use correlates of protection to predict who is protected for how long, and against what COVID-disease manifestations, we need to stick with the notion of trying to protect the most vulnerable people with adapted boosters,” Kampmann said. 

German biotech Curevac has filed a lawsuit against its counterpart BioNTech, claiming the COVID-19 vaccine co-developed with Pfizer infringes four of Curevac’s mRNA patents.

While moving to assert its rights, CureVac said it is not seeking an injunction nor does it intend to take legal action that impedes the production, sale or distribution of the vaccine by BioNTech and Pfizer.

Rather, in the lawsuit filed in the German Regional Court in Düsseldorf against BioNTech and two of its subsidiaries, Curevac is seeking fair compensation for infringement of a portfolio of intellectual property rights it says BioNTech used in the manufacture and sale of the vaccine, Comirnaty.

The patents in question relate to the engineering of mRNA molecules, including sequence modifications to increase stability and enhance protein expression, as well as mRNA vaccine formulations specific to SARS CoV-2 vaccines, according to Curevac.

In response, BioNTech said it, “values and respects valid intellectual property rights,” but the work is original. “We will vigorously defend it against all allegations of patent infringement. However, we are aware that it is not unusual that other companies in the pharmaceutical industry, having witnessed the success of Comirnaty are now suggesting that the vaccine potentially infringes their intellectual property rights,” BioNTech said.

Before the pandemic struck, both companies were applying mRNA to develop cancer vaccines. They pivoted to developing COVID-19 vaccines when the pandemic took hold, with BioNTech forming its partnership with Pfizer on the back of an existing research collaboration between the two in influenza.

Curevac gave up on its first mRNA-based COVID-19 vaccine due to lack of efficacy, but now has another one it is co-developing with GlaxoSmithKline.

European Centre for Disease Prevention and Control (ECDC) and the European Medicines Agency (EMA) are recommending that second booster doses of mRNA COVID-19 vaccines be considered for people between 60 and 79 years old and people with medical conditions putting them at high risk of severe disease.

This follows on from the recommendation in April 2022 that people over 80 years of age be considered for a second booster. At that time EMA said it might be necessary to consider second boosters in people between 60 and 79 years old and vulnerable persons of any age if there was a resurgence of infections.

With a new wave of infections driven by the Omicron variants BA.4 and BA.5 now underway in Europe, with increasing rates of hospital and intensive care unit admissions, EMA says it is “critical” that public health authorities in member states now consider people between 60 and 79 as well as vulnerable persons of any age for a second booster.

These could be administered at least four months after the previous one, with a focus on people who have received a previous booster more than 6 months ago.

Stella Kyriadkides, European Commissioner for Health said there is no time to lose. “I call on member states to roll-out second boosters for everyone over the age of 60 as well as all vulnerable persons immediately and urge everyone eligible to come forth and get vaccinated.”

“We are currently seeing increasing COVID-19 case notification rates and an increasing trend in hospital and ICU admissions and occupancy in several countries mainly driven by the BA 5 sublineage of Omicron,” said Andrea Ammon, director of ECDC.

This signals the start of a new, widespread COVID-19 wave across the EU. “There are still too many individuals at risk of severe COVID-19 infection whom we need to protect as soon as possible […] We have to start today.”

At the moment, there is no clear evidence to support giving a second booster dose to people below 60 years of age who are not at higher risk of severe disease. Neither is there clear evidence to support giving early second boosters to healthcare workers or those working in long-term care homes, unless they are at high risk.

However, residents at long-term care homes are likely to be at risk of severe disease and should be considered for booster doses in line with national recommendations.

The latest ECDC/EMA advice comes amid work to adapt vaccines for the Omicron variants of concern.

“We are working towards possible approvals of adapted vaccines in September,” said EMA’s executive director, Emer Cooke. “Our human medicines committee is currently reviewing data for two adapted vaccines.”

Further details about the latest advice on second booster doses is in the ECDC/EMA joint statement.

A new global hub for genomic surveillance launched by the Wellcome Sanger Institute will work with partners around the world to use genome sequencing to help tackle infectious diseases.

The Genomic Surveillance Unit (GSU) will help partners to develop their own genomic surveillance capabilities, enabling them to generate information about infectious pathogens in circulation and their characteristics.

The surveillance will involve sequencing the genomes of pathogens to track evolutionary changes that affect transmission, disease severity and susceptibility to treatment.

The use of genomics for surveillance was very much in its infancy before the outbreak of the COVID-19 pandemic, having largely been used to map the emergence of antimicrobial resistance.

The technique has gained widespread visibility during the pandemic, with sequencing of SARS-CoV-2 viral genomes providing an invaluable tool to track the spread of the virus and emergence of new variants.

The mission of the GSU is to accelerate the generation of genomic data on a large scale. It will do this by working with partners to implement scientific pipelines, from sample collection through to the delivery of data. In particular, the unit will focus on strengthening capacity for the generation and sharing of genomic data, developing easy-to-use tools and methods, and creating accessible resources that provide actionable information for public health.

Mike Stratton, director of the Sanger Institute, said, “It is critical that the lessons learned and extraordinary experience acquired during the COVID-19 pandemic are not lost, but rather used to drive forward the development of effective genomic surveillance across the globe.”

While truly worldwide infectious disease genomic surveillance networks would be a huge boost to global health capability and pandemic preparedness, the cost and complexity of such programmes can be prohibitive. Making genomics more accessible and easier to scale will be vital if its potential as a practical tool for infectious disease control is to be realised for all.

John Sillitoe, director of the GSU said, “We are passionate about working with our partners to achieve their vision for integrating genomic surveillance into their scientific and public health infrastructure.”

A new consortium has been formed to design a vaccine that is effective against both SARS-CoV-2 and a number of related bat viruses that have the potential to spread to humans.

The project builds on technologies developed by the Molecular Immunology Group at Oxford University, a group based at Caltech in the US, and by researchers at the UK Medical Research Council’s Human Immunology Unit.

The Coalition for Epidemic Preparedness Innovations (CEPI), will partner with the consortium and has announced up to $30 million to fund preclinical studies, manufacturing and a phase I trial.

In contrast to a number of the existing COVID-19 vaccines that use mRNA or a viral vector to present sections of the spike protein of the virus that emerged in Wuhan, China, to the immune system, the new vaccine will use protein nanoparticles loaded with antigenic sections of the spike proteins from eight different viruses, held together by a molecular ‘glue’. It is hoped that will generate immune responses to the shared parts of each of the different types of coronaviruses within a single vaccine.

There also is evidence that indicates this approach will not only elicit protective immune responses against SARS-like viruses but also against some coronaviruses not presented in the trial vaccine. There is a suggestion that could provide protection against future novel SARS-CoV-2 variants and other coronaviruses with the potential to spill over from animal populations.

The Oxford lead of the consortium, Alain Townsend, professor of molecular immunology said, “The evolution of this consortium is an example of collaborative science at its best. We had been deeply impressed by the power of the ‘glue’ for sticking proteins together. Together we used this technology to make a prototype nanoparticle SARS-CoV-2 vaccine that induced highly potent responses in preclinical studies.”

A new Pandemic Sciences Institute opened its doors at Oxford University this week, to take forward the lessons and experience of responding to COVID-19 in countering future pandemic threats.

The Institute will harness the university’s research and global research collaborations and partnerships developed over decades between academia and industry. Although based in the medical faculty it will draw together researchers from across the Oxford University, including veterinary sciences and social sciences. The work it carries out will span from basic science to implementation of interventions.

The director of the institute is Peter Horby, professor of Emerging Infections, who led the UK Recovery trial, which amongst other advances found the steroid dexamethasone is an effective treatment for COVID-19. That was the first drug to be shown to have a therapeutic effect against the disease.

“During the COVID pandemic, diagnostic tests, drugs and vaccines were developed and deployed at speeds that were previously unthinkable, and we benefited from remarkable insights into epidemiology, biology and behaviour in near real time,” Horby said. “The Pandemic Sciences Institute aims to make such exceptional achievements routine and ensure the benefits are shared by all. We believe that we can make the world a safer place for everyone by uniting disciplines and sectors to tackle complex infectious disease threats together.”