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

02 Jun 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.

A team led by the Technical University of Munich (TUM) has successfully used a specific enzyme to destroy the genetic information of SARS-CoV-2 directly after the virus penetrates human cells. The researchers say this could provide the basis of a therapy to treat COVID-19.

The approach depends on harnessing RNA-Induced Silencing Complex (RISC), an enzyme which cuts viral RNA.

Efforts have been made for quite some time now to make therapeutic use of this mechanism. The researchers set out to discover how viral RNA can be best attacked using RISC, and at which stage of the replication cycle treatment should take place.

They found that RISC is most effective when the virus has just penetrated a human cell.

The researchers tested their approach in human lung tissue, confirming the results and are now planning to develop a method for delivering the enzyme directly to the lungs in an inhaled formulation.

Researchers at Aston University in the UK have helped develop a mathematical model which can estimate daily transmission rates of COVID-19 and other infections by testing for antibodies in blood collected at blood donation centres.

They say it is a faster way to assess transmission than existing epidemiological models, and can be used to assess infection rates in the absence of population level testing for COVID-19 infections.

The Aston researchers worked with counterparts at the Universidade Federal de Minas Gerais in Brazil to apply their models to results obtained from Brazilian blood donor centres. The testing was done by Fundacao Hemominas, one of the largest blood services in Brazil, which covers an area similar to that of continental France.

They used the reported number of SARS-CoV-2 cases along with data on anti-SARS-CoV-2 antibodies in blood donors, to determine daily transmission rates and cumulative incidence rate of reported and unreported cases.

The model gave the experts the ability to have higher level view of infection rates and the relative rate of immunity, compared to official measurements.

The antibody testing started at the beginning of the pandemic and involved 7,837 blood donors in seven cities during March–December 2020. At that point COVID-19 diagnostic testing wasn’t widely available and there was a high proportion of undetected asymptomatic or light symptomatic cases. The data obtained allowed the experts to estimate the proportion of people who were going undiagnosed.

“Public communication about the COVID-19 epidemic was based on officially reported cases in the community, which strongly underestimates the actual spread of the disease in the absence of widespread testing,” said Felipe Campelo, senior lecturer in computer science at Aston University. “This difference underscores the convenience of using a model-based approach such as the one we proposed, because it enables the use of measured data for estimating variables, such as the total number of infected persons.”

The model delivers daily estimates of relevant variables that usually stay hidden, including the transmission rate and the cumulative number of reported and unreported cases of infection, Campelo said.

From July 2020 there was a sharp increase in the number of people tested for COVID-19 in Brazil, as new infrastructure became available. This allowed the experts to further validate their methodology by observing how officially recorded data became closer to the model predictions once testing became more widespread, including for asymptomatic or mildly symptomatic people.

In future, the researchers aim to improve the accuracy of the model by introducing changes to account for vaccination effects, waning immunity and the potential emergence of new variants.

An international research team has developed a new theoretical model to better assess the risks of spreading viruses such as COVID-19, with and without a face mask.

The results show the standard ‘safe’ distance of two metres does not always apply, and in fact varies greatly depending on a range of environmental factors, and that face masks can indeed play a crucial role.

Modelling the direct virus exposure risk associated with talking, coughing and sneezing, the research shows it is possible to calculate the direct risk of spreading COVID-19 infection, by including factors such as interpersonal distance, temperature, humidity levels and viral load, and to demonstrate how these risks change with and without a face mask.

For example, a person talking without a face mask can spread infected droplets one metre away. Should the same person cough, the drops can be spread up to three metres, and if the person sneezes, the spread distance can be up to seven metres.

But using a face mask, the risk of spreading infection decreases significantly. Provided the face mask is worn correctly, the risk of infection is negligible even at distances as short as one metre, regardless of environmental conditions, and if an infected person is talking, coughing or sneezing.

The model uses data from recent experiments on droplet emissions, enabling the researchers to take several factors into account and quantify the risk of infection, with and without a face mask.

The study was led by the University of Padua, in collaboration with the University of Udine, the University of Vienna and Chalmers University of Technology.

The regulation reinforcing EMA’s role in crisis preparedness and management of drug and medical device supplies has come into force today, putting some of the structures and processes established by EMA during the COVID-19 pandemic on a more permanent footing.

EMA is now responsible for monitoring drug supplies and reporting shortages of critical drugs during a crisis. From 2 February 2023, it will have a similar role in medical devices.

To ensure a robust response to serious shortages, a Medicines Shortages Steering Group, will be set up.

In addition, a standing Emergency Task Force will provide scientific advice on the development of products intended for use during a public health emergency; review scientific data; provide recommendations on the use of drugs that do not have formal regulatory approval; and coordinate independent vaccine effectiveness and safety monitoring studies.

The composition and rules under which the medicines shortages group and the emergency task force operate are due to be endorsed by EMA’s management board in March.

A further preparedness measure will involve updating the role of the EU Single Point of Contact (SPOC) network, the system that EMA and national regulators use to exchange information on shortages.

Under the new mandate, SPOC will make recommendations on all matters relating to monitoring and management of shortages and availability issues during a crisis, and provide guidance to companies.

Researchers at the Max Planck Institute for Human Development, Germany, with collaborators at the Plymouth University, UK, and the IESE Business School, Spain have developed a game they say can test in advance the effectiveness of control measures to slow the spread of SARS-CoV-2.

The study found the most effective approach was a message that directly appealed to the public, contained moral reason, and was clear and consistent.

The research, published in Science Advances, involved seven groups of 100 people from a cross section of the US population playing a game designed to emulate virus transmission. It integrated simulations of outbreak dynamics with monetary stakes for the players.

Blue players represented healthy individuals, and purple players infected individuals. The aim of the game was to stay blue.

If players took more risks and managed to stay blue, they got a higher reward. However, if they got ‘infected’ and turned purple, they lost everything.

The interventions in the game implemented principles used by countries worldwide to persuade people to comply with pandemic control measures.

The study showed that the most effective way to reduce risk-taking behaviour was a message with a simple imperative backed by a moral explanation, for example, ‘choose this action to protect your and other players’ money’. On average, participants who responded to these instructions also earned the highest amount of money.

Showing the case rate numbers, that is how many players were purple, had no effect on behaviours, nor did saying how many participants were choosing less risky behaviours. That actually led to a slight increase in risk-taking behaviour overall.

“Non-pharmaceutical interventions, such as wearing masks, maintaining physical distance, and reducing contacts, require large-scale behaviour change, which depends on individual compliance and cooperation,” said lead author Jan Woike, lecturer in psychology at Plymouth University. “The behavioural sciences offer cognitive and communication tools to help, but the effectiveness of methods to increase compliance has rarely been tested in controlled scenarios that reflect the dynamics of infectious outbreaks.”

What is important about the transmission game is that it makes it possible to test the effectiveness of an intervention before implementing it in a real pandemic.

“It was interesting to note that the most effective intervention was not the one that participants liked the most. Clear and consistent messaging worked best in reducing risk-taking behaviours,” Woike said.

Scientists at the Max Planck Institute for Medical Research in Heidelberg and their collaborators at the Max Planck Centre for Minimal Biology at Bristol University have developed a new approach to studying SARS-CoV-2, after creating a stripped down version of the virus, or virion, to which they can now attach distinct structures, such as the spike protein by which the virus enters human cells.

This has enabled them to study individual molecular mechanisms in a controlled setting, which they can further manipulate and tune.

Using this technique to study the spike protein they have discovered a switching mechanism, showing that upon binding of inflammatory fatty acids, the spike protein changes its conformation, thereby becoming less visible to the host immune system.

The synthetic construct also overcomes safety concerns about handling live virus because the virions have a similar structure to natural viruses but do not contain any genetic information.

“Even more important for us, as we build these synthetic virions from scratch, is that we can precisely design their composition and structure. This allows us to perform a very systematic, step-by-step study on distinct mechanisms”, said Oskar Staufer, first author of the paper describing the research.

The inflammatory fatty acids that are released during any inflammation in the body help spark the immune response and healing processes. While it was known that the spike protein has a distinct region where inflammatory fatty acids can bind, the function of this binding pocket was previously not understood.

Using the virions, the researchers were able to show that upon binding of a fatty acid, the spike protein changes its conformation and folds, becoming less visible to the immune system. As a result, fewer antibodies bind to the spike protein. Following on from this discovery, the researchers are now assessing if it can inform the development of antiviral therapies.

Sanofi and GlaxoSmithKline have announced they are now ready to submit the file for approval of their jointly developed COVID-19 vaccine, after reporting positive results in phase III efficacy trials and of its use as a booster.

The data show the vaccine induced robust immune responses and had a favourable safety profile in multiple settings. In participants who had received two doses of an mRNA or adenovirus vaccine, the Sanofi-GSK booster vaccine induced a significant increase in neutralising antibodies across different vaccines and age groups.

When the Sanofi-GSK vaccine was used as a two-dose primary series followed by a booster dose, neutralising antibodies also increased significantly.

“The Sanofi-GSK vaccine demonstrates a universal ability to boost all platforms and across all ages. We also observed robust efficacy of the vaccine as a primary series in today’s challenging epidemiological environment,” said Thomas Triomphe executive vice president, Sanofi Vaccines. “No other global phase III efficacy study has been undertaken during this period with so many variants of concern, including Omicron.”

The companies are now in discussions with regulators, including the US FDA and European Medicines Agency.

Scientists at the Medical University of Vienna have published data showing people who are dual vaccinated or have recovered from a natural COVID-19 infection have virtually no protection against the currently circulating Omicron variant of SARS-CoV-2.

The research indicates only individuals who have received a third booster dose of vaccine generate antibodies that can partially block Omicron.

In a study led by Rudolf Valenta at the Institute of Pathophysiology and Allergy Research, an Austrian subpopulation of vaccinated and recovered individuals was examined for antibody status and protection against the Wuhan, Delta and Omicron variants of SARS-CoV-2. The researchers tested whether the virus can bind to the ACE2 receptor on human cells via its receptor binding domain (RBD) in people immunised with all vaccines and vaccine combinations currently licensed in Austria.

The results showed that both COVID-19 convalescent individuals and individuals who had been vaccinated twice, had developed antibody protection against Delta. However, the antibodies were not able to block binding of the RBD of Omicron.

Blockade of Omicron was better in those individuals who had received a third vaccination. "The third vaccination developed protective antibodies in many individuals," said Valenta. “However, there is also a significant proportion (20%) in whom no protection was established.”

The RBD in variants that emerged before Omicron differed only slightly from one to the other, so that infections with these variants and immunisation with the currently available vaccines provided protection. Omicron is the first variant that differs greatly from the previous variants in its RBD, consequently infection with earlier variants, and currently available vaccines, provide little or no protection against it.

Little has been known to date about how the immune system’s natural killer (NK) cells detect which cells have been infected with SARS-CoV-2. Now an international team led by researchers from Karolinska Institutet have shown that NK cells respond to a particular peptide on the surface of infected cells.

The study, which is published in Cell Reports, is an important piece of the puzzle in understanding how the immune system reacts to COVID-19.

Unlike antibodies, NK cells are able to recognise and kill virus-infected cells immediately, without having encountered them before. This ability is controlled by a balance between activating and inhibiting receptors on NK cells, which can react to different molecules on the surface of other cells.

The research shows cells infected with SARS-CoV-2 carry on their surface a peptide from the virus that triggers a reaction in NK cells carrying a receptor, NKG2A, which is able to detect the viral peptide.

The study involved collaboration between the Karolinska and laboratories and universities in Italy, Germany, Norway and the US. In the first phase, the researchers used computer simulations that were then confirmed in the lab by infecting human lung cells with SARS-CoV-2 in a controlled environment. That made it possible to demonstrate that NK cells with the NKG2A receptor are activated to a greater degree than the NK cells without it.

The study is now being followed up using a biobank at the Karolinska containing blood samples from over 300 people treated for COVID-19 during the first wave of the pandemic, to assess if the composition of NK cells in a given patient contributed to how severe their symptoms were when infected with SARS-CoV-2.

Researchers at the University of Seville have devised a new highly accurate optical method for detecting SARS-CoV-2 in saliva from COVID-19 patients.

It has also been possible to detect SARS-CoV-2 in saliva of asymptomatic people.  The main advantage of the new technology over PCR is in the speed of sample processing and the ability of the optical system to simultaneously analyse a large number of samples.

The researchers have demonstrated proof of concept in the lab and are currently working on validating the new methodology, which detects virus with high sensitivity imaging and data processing based on advanced statistics and artificial intelligence.

Multiple samples can be processed simultaneously, without contact or reagents and with relatively simple equipment that requires minimal training to operate.

Details of the proof of concept study were published in Nature Scientific Research earlier this month.

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