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

New preclinical data for a COVID-19 vaccine developed at the Medical University of Vienna indicates that it is effective against all SARS-CoV-2 variants known to date, including Omicron.

The antigen-based vaccine developed by a team led by Rudolf Valenta at the Centre for Pathophysiology, Infectiology and Immunology, targets the receptor binding domain (RBD) of the SARS-CoV-2 virus, inducing a robust and uniform RBD-specific IgG antibody response in animal models and in human serum samples. The antibody response prevents the virus from docking onto and entering the body's cells, so that infection cannot occur.

The vaccine has the potential, “to induce sterilising immunity to old and new SARS-CoV-2 variants by stopping viral replication and transmission through the inhibition of cellular virus entry,” said Valenta.

It is expected that the vaccine will be effective in people who have not previously responded to vaccination, as it will generate additional T-cells.

The development of the Austrian COVID-19 vaccine was inspired by decades of previous in allergy vaccine design.

"Our data give us grounds to hope that this readily producible protein-based vaccine antigen will be effective against all SARS-CoV-2 variants known to date, including Omicron," Valenta said. "The vaccine is designed to enable repeated injections to build up sustained sterilising immunity, is suitable for use in all age and risk groups, and appears to be superior to currently available vaccines when it comes to inducing neutralising antibodies."

If sufficient funding is forthcoming, the first clinical trials could be carried out this year.

Throughout the COVID-19 pandemic, so-called nudges prompted people to adopt simple behaviours in the name of public health.

These include fist bumps in place of shaking hands and standing six feet apart.

This indicates insights from behavioural science can inform the design of effective behaviour change techniques, to influence individual behaviour.

Ivo Vlaev at Warwick University worked with members of the UK government’s Behavioural Insights Team to develop Mindspace, a framework that was used to guide effective policy drawing on the latest insights from behavioural sciences and nudge theory.

In a paper reviewing the use of Mindspace during the early months of the pandemic, Vlaev and co-authors highlight examples of nudges used in the early months of the COVID-19 pandemic and summarise their effectiveness.

The evidence is that nudges work and are a powerful social science tool amidst a pandemic. 

“Organisation leaders, policymakers, and practitioners can use nudges to promote public health when mandates are not politically feasible or enforceable,” the paper says.

The lockdown measures imposed across Europe in March 2020 to contain the COVID-19 pandemic led to unprecedented declines in air pollution and noise, but also of physical activity levels in cities.

The consequences of these changes for people's health differed depending on the stringency of the confinement measures and local context, according to new research by the Barcelona Institute for Global Health.
 
To compare different contexts, the research team looked at three European cities with different degrees of lockdown: Barcelona, where a strict lockdown was imposed including law-enforced home confinement; Stockholm, where the measures were much more relaxed and subject to individual responsibility; and Vienna, which had intermediate measures.
 
For each of the three cities, they collected or estimated data on air pollution, noise and physical activity from three different points in time: before the pandemic, during lockdown and in the subsequent period when restrictions were relaxed.
 
It was shown that the strictness of the confinement measures was directly related to the decline in exposure to noise and pollution and amount of exercise. Barcelona, the city facing the greatest restrictions was also the one that recorded the largest decreases in air and noise pollution and physical activity. Specifically, during the first lockdown, nitrogen dioxide concentrations fell by 50% on average, daily noise levels were reduced by 5 decibels and physical activity was reduced by 95%.
 
During the same period, in Vienna, NO2 pollution fell by 22%, and average daily noise levels were reduced by 1 decibel, while physical activity fell by 76%.
 
For Stockholm, NO2 levels fell by 9%, noise levels were reduced by 2 decibels and physical activity fell by 42%.
 
Drawing on evidence from previous studies, physical activity was the main driver of health outcomes, the researchers conclude. Extending strict confinement in Barcelona for a full year would have resulted in a 10% increase in strokes and heart attacks and an 8% and 12% increase in diagnoses of depression and anxiety, respectively, due to the reductions in physical activity.

Reduction of physical activity in Vienna for a whole year could have led to a 5% increase in the annual incidence of strokes and heart attacks, as well as 4% and 7% increase in diagnoses of depression and anxiety, respectively.
 
Even in Stockholm, the city with the slightest decline in physical activity levels, there would have been negative health effects if the situation had lasted for a year. The model estimated a 3% increase in the respective incidences of strokes and heart attacks, 2% more diagnoses of depression and 3% additional cases of anxiety.
 
On the other hand, if the reduction in NO2 concentrations from the first lockdown had been sustained for a whole year, an estimated 5% of heart attacks, 6% of strokes and 11% of depression diagnoses could have been prevented in the city of Barcelona. In Vienna, the estimated decreases would be 1% for strokes and heart attacks and 2% for depression.  

In Stockholm the positive health impact would be the prevention of 1% of depression diagnoses.

Lower noise levels over one year in Barcelona could have prevented an estimated 4% of annual heart attacks, 7% of strokes and 4% of diagnosed depression. In Vienna, the incidence of myocardial infarction, stroke and depression could have been reduced by 1%. And finally, for Stockholm, a 2% reduction in diagnosed heart attacks and depression, and a 4% reduction in stroke cases related to noise reduction is estimated.
  
“Despite the differences observed in the three cities, there is a common pattern: the health benefits of improved air quality and noise fail to offset the profoundly negative effects of reduced physical activity levels,” said Sarah Koch, first author of the study.

An electrocardiogram (ECG) can pinpoint those hospitalised COVID-19 patients who are at high risk of death and might need intensive management, according to a study presented at the European Heart Rhythm Association meeting in Copenhagen on Monday.

Specifically, the research showed that a prolonged QT interval – a measure of the electrical activity of the heart - is an independent risk factor for both myocardial injury and one-year mortality.

“An ECG is an inexpensive, non-invasive, easily attainable and widely available test applied in nearly all hospitalised patients,” said Ariel Banai of Tel Aviv Sourasky Medical Centre, Israel. “Our study suggests that a simple ECG tracing performed upon admission may help healthcare professionals to triage patients with COVID-19 and identify those in need of intensive care.”

The QT interval refers to the electrical signal from the moment the ventricles of the heart contract until they finish relaxing, and is measured in milliseconds. Patients with a prolonged QT interval are at increased risk for life-threatening arrhythmias (heart rhythm disorders) and cardiac arrest.

This study examined the association between QT prolongation and long-term mortality in patients hospitalised with COVID-19. It also evaluated the relationship between prolonged QT interval and myocardial injury, in which cells in the heart die.

A total of 335 consecutive patients hospitalised with COVID-19 were prospectively studied. All patients had an ECG upon admission.

At one year, 41% of patients in the prolonged QT interval group had died, compared to 17% in the normal QT interval group.

Banai said, “In our study, one-third of hospitalised COVID-19 patients had a prolonged QT interval. These patients were generally older and sicker, but even after adjusting for these factors, prolonged QT interval was independently associated with worse survival. More studies are needed to confirm our observations, but the results indicate that ECG assessment could play a role in the risk stratification of patients admitted with COVID-19 infection.”

SARS-CoV-2 has spread from humans to white-tailed deer in North America and the animals are now considered reservoirs from which the virus could spill back to humans.

However, a team headed by researchers at the Leibniz Institute for Zoo and Wildlife Research has now shown this has not happened in Germany and Austria, and all deer tested were negative for SARS-CoV-2 antibodies.

The spread from humans to deer is a cause of concern, since novel variants could evolve in the new deer host and eventually spill back to humans. While white-tailed deer are a North American species, deer occur worldwide, and in central Europe like North America, are heavily hunted and managed. 

The scientists examined blood samples from 433 roe, red and fallow deer, both pre-pandemic and collected during the pandemic, for SARS-CoV-2 antibodies using an assay that previously confirmed antibody levels in North American deer. None of the deer from Germany or Austria were positive.

The team also compared the ACE2 receptor via which the virus enters host cells. With the exception of one change which might potentially make red deer somewhat more resistant to infection, no changes were found in the receptor in the European species that could account for the difference in results between central European and North American deer exposure.

The likely explanation for the differences relates to how deer are distributed and managed in North America compared to central Europe. In North America, deer are often peri-urban and urban, with high potential levels of contact with humans and human waste. Deer are managed principally by the federal government.

In Germany and Austria, deer are generally not peri-urban or present in urban settings and the system for granting hunting licenses mean deer in a specific area are locally managed. These factors limit human-deer contact and also hinder the spread of pathogens among deer populations.

“Every effort should be made to maintain barriers to human-deer contact in central Europe to prevent the establishment of deer as a SARS-CoV-2 reservoir,” said Alex Greenwood, co-author of the paper describing the research. 

Some people who recover from COVID-19 pneumonia have evidence of damage to their lungs that persists a full year after the onset of symptoms, according to a new study by clinicians in Austria.

While COVID-19’s short-term effects on the lungs are well documented, much less is known about any long-term effects.

The researchers looked at patterns and rates of improvement of chest CT abnormalities in patients one year after COVID-19 pneumonia. They assessed 91 participants, mean age 59 years, at several points over one year after the onset of symptoms.

At one year, abnormalities were present in 49 participants. Of these, 49 two had received outpatient treatment only, 25 were treated on a general hospital ward and 22 had received intensive care.

“The observed chest CT abnormalities from our study are indicative of damaged lung tissue,” said study co-author Anna Luger of the Department of Radiology at Innsbruck Medical University. “It is currently unclear if they represent persistent scarring, and whether they regress over time or lead to pulmonary fibrosis.”

While the abnormalities decreased in initial follow-up, 63% of those affected did not show any further improvement after six months.

Evidence from the SARS-CoV-1 outbreak of 2002 to 2004 shows that lung abnormalities may remain detectable even after decades, but do not show any progression. However, more recent studies have shown a risk of progression.

“We were able to show that the severity of acute COVID-19, protracted systemic inflammation and the presence of residual chest CT abnormalities are strongly related to persistently impaired lung function and clinical symptoms,” said study co-author Christoph Schwabl of Innsbruck Medical University.

Lightbulbs that are already in use in offices and public spaces can destroy coronaviruses and HIV, according to a new study from Toronto University.

Researchers killed both viruses using UV-LED lights, which can alternate between emitting white light and decontaminating ultraviolet light. With a cheap retrofit, they could also be used in many standard lighting fixtures, giving them a “unique appeal” for public spaces, said Christina Guzzo, senior author of the study.

Guzzo first tested the lights on bacterial spores that are notorious for their resistance to ultraviolet light.

“If you're able to kill these spores, then you can reasonably say you should be able to kill most other viruses that you would commonly encounter in the environment,” Guzzo said.

Within 20 seconds of UV exposure, growth of the spores dropped by 99%.

The researchers then created droplets containing coronaviruses, to mimic typical ways people encounter viruses in public, from coughing and sneezing. The droplets were then exposed to UV light and placed in a culture to see if any of the virus remained active. With just 30 seconds of exposure, the virus’ ability to infect dropped by 93%.

Guzzo also compared UV light to two heavy duty disinfectants used in lab research, showing UV lights were similarly effective in their ability to deactivate viruses.

“I was really surprised that UV could perform on the same level of those commonly used lab chemicals, which we regard as the gold standard,” Guzzo said.

UV-LEDs are cheap and could be easy to retrofit in existing light fixtures, and the bulbs are long-lasting and simple to maintain.  

However, repeated, prolonged exposure to UV radiation is harmful. Guzzo suggested UV lights should be used when public spaces are empty, such as vacated buses that have finished their routes, or empty elevators. Escalator handrails could be continuously disinfected by putting UV lights in the underground part of the track, cleaning it with each rotation.

Safe Antivirus Technologies, a Toronto-based start-up company that worked with Guzzo on the study, is developing UV-LED lighting modules with motion sensors. The lights automatically switch to UV light when a room is empty, then turn back to regular light when there is movement.

The European Medicines Agency (EMA) is advising companies running clinical trials affected by the war in Ukraine to use the experience gained during the COVID-19 pandemic and apply the same approaches and flexibilities.

More than one month after the war started, this is the first advice from the European Commission, the EMA and the heads of national medicines agencies on how to manage the conduct of clinical trials in Ukraine.

EMA says certain changes and protocol deviations in the current situation are unavoidable, when for example scheduled study visits cannot take place, or arrangements need to be made to transfer trial participants who are fleeing Ukraine to other investigator sites of the same trial in the EU.

Clinical trial sponsors have also asked for guidance on how to handle the situation in terms of trial records, documentation, data collection, protocol deviations, and missing data with its potential impact on methodological aspects.

Scientists at the Karolinska Institutet say they have developed a new way of discovering antibody fragments, called nanobodies, against emerging SARS-CoV-2 variants.

They have found multiple nanobodies that block infection with different SARS-CoV-2 variants in human cells and mice.

Despite the roll-out of vaccines and antivirals, the need for effective therapeutics against severe COVID-19 infection remains high. Nanobodies offer several advantages over conventional antibodies because they have a long half life in the blood stream, are better able to penetrate tissues and are easier and cheaper to manufacture.

In a paper published in Nature Communications, the researchers describe a single nanobody, Fu2, that significantly reduced the viral load of SARS-CoV-2 in cell cultures and mice. Using electron cryomicroscopy, they found that Fu2 naturally binds to two separate sites on the viral spike protein, thus inhibiting the virus’ ability to enter the host cell.

A second paper in Science Advances describes additional nanobodies that in cell cultures and mice effectively cross-neutralised both the founder and beta variant of SARS-CoV-2 and the more distantly related SARS-CoV-1.

The researchers are now applying the same techniques to identify nanobodies that are able to neutralise the Omicron variant.

Adults in hospital who have COVID-19 and the flu at the same time are at much greater risk of severe disease and death compared to patients who have COVID-19 alone, according to new research.

Patients co-infected with SARS-CoV-2 and influenza were over four times more likely to require ventilation support and 2.4 times more likely to die than if they only had COVID-19.

Researchers say this shows there is a need for more flu testing of people admitted to hospital with COVID-19.

The team from Edinburgh, Liverpool and Leiden universities and Imperial College London, made the finding based on more than 305,000 hospitalised patients with COVID-19.

The research, which is part of the International Severe Acute Respiratory and emerging Infection Consortium’s Coronavirus Clinical Characterisation Consortium, is the largest ever study of people with COVID-19 and other endemic respiratory viruses.

Kenneth Baillie, professor of experimental medicine at Edinburgh University said, “We found that the combination of COVID-19 and flu viruses is particularly dangerous. This will be important as many countries decrease the use of social distancing and containment measures. We expect that COVID-19 will circulate with flu, increasing the chance of co-infections. That is why we should change our testing strategy for COVID-19 patients in hospital and test for flu much more widely.”