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

Scientists and engineers at the University of Granada have developed and tested a ‘smart’ FFP2 facemask that notifies the user via their smartphone when the permitted carbon dioxide limits inside the mask are exceeded.

This addresses a problem that has been particularly highlighted since the COVID-19 pandemic began, of re-inhaling previously exhaled CO2 trapped inside facemasks.

Wearing FFP2-type facemasks for any length of time produces a concentration of CO2 between the face and the mask that is higher than the normal atmospheric concentration. CO2 rebreathing can cause adverse effects, even in healthy people, such as general malaise, headaches, fatigue, shortness of breath, dizziness, sweating, increased heart rate, muscle weakness, and drowsiness.

These negative effects are known to be linked to both the duration of exposure and the concentration of the gas. Some health regulations recommend a maximum value of 0.5% CO2 in the working environment (averaged over an 8-hour day), or that a 30 minute exposure to 4% CO2  be considered very harmful to health.

“Notwithstanding the generalised evidence in favour of facemasks to reduce transmission throughout the population, there is also broad agreement on the possible adverse effects caused by their prolonged use, mainly as a consequence of the increase in respiratory resistance and the re-inhalation of the CO2 that accumulates inside the mask,” the researchers say.

The new FFP2 facemask with a flexible, integrated opto-chemical gas sensor designed at the University of Granada makes it possible to ascertain the level of CO2 rebreathed in real time, using a smartphone application. This is low cost, scalable, reliable, and convenient, the researchers say.

Details of the design are published in Nature Communications.

A COVID CXR Hackathon has been launched by the Italian Institute of Technology, Fondazione Bruno Kessler and the University of Modena and Reggio Emilia, with an invitation to the international scientific community to apply the most advanced software and analysis models of artificial intelligence to the interpretation of COVID-19 clinical data, with the aim of making the work of doctors in hospital wards easier, and ease the strains the pandemic has put on health systems.

The organisers of the hackathon say automated or semi-automated techniques developed using machine learning could help doctors tell which patients can be treated safely at home, improving planning and allocation of resources.

Participants in the hackathon will have to develop systems capable of processing real data gathered from hospitalised patients in the first wave of the pandemic in early 2020.

The winning proposals will not only be accurate, but must operate in a way that is transparent and understood by healthcare providers who are not artificial intelligence experts. The contributions will be evaluated by a team of doctors and computer scientists.

Alessio Del Bue, head of Pattern Analysis and Computer Vision at the Italian Institute of Technology in Genoa said, “COVID CXR Hackathon was designed to transform the pandemic experience into a driver for the scientific community to show that the development of automated intelligent systems, both for the recognition of images and other types of data, is ready to face the most pressing problems of our society. Discussion with clinicians, companies and industry is critical.”

Disease models play a major role in COVID-19 research, allowing the study of disease mechanisms and preclinical development of vaccines and treatments. Now a research group at the Medical University of Vienna has developed a new way of modelling COVID-19 in mice, which closely mimics how humans react to the SARS-CoV-2 virus.

There are many similarities between the immune systems of mice and humans, meaning in general that mice make good models of human disease.

However, because of specific genetic and structural differences between mice and humans in the ACE2 receptor by which SARS-CoV-2 enters the host cells, mice are not readily infected with virus variants isolated from human COVID-19 patients.

The researchers have taken SARS-CoV-2 from a human patient and modified it so it can bind to murine ACE2. Animals infected by the modified virus develop symptoms of COVID-19, allowing the study of disease mechanisms and of potential treatments.

It was shown that the immune response in infected mice is similar to that seen in humans.

As an example of the utility of the model, the researchers demonstrated that synthetically produced ACE2, administered by inhalation, can protect against SARS-CoV-2 infection.

A warning issued last year by the US Food and Drug Administration drew attention to research showing pulse oximeters that detect blood oxygen levels by shining light through the skin give inaccurate readings in people with darker skin colour.

Now researchers at Nottingham University have quantified the levels of false readings and are about to investigate the impact this has on patients getting the treatment they need, when they need it

The research, published in the European Respiratory Journal, shows that pulse oximeters recorded oxygen levels of nearly 7% higher than was the fact in a group of patients of mixed ethnicity with COVID-19. That compared over-stating oxygen levels in white patients by 3%.

There were also false high readings in patients with of both Black and Asian ethnicity. Levels of blood oxygen are one of the key ways of assessing the severity of COVID-19 infections, and these incorrect measurements could delay people being admitted to hospital and receiving the best and most timely treatment.

The researchers used electronic datasets that are collected for clinical use in real time, but archived and available to answer important clinical questions and improve both patient care and safety.

They compared the difference in blood oxygen levels as measured by pulse oximetry and by arterial blood gas tests, which involve measuring oxygen levels directly in a blood sample.

There were differences in oxygen levels between the pulse oximetry and arterial blood gas readings in all groups. The highest difference was in the mixed ethnicity group, which was nearly 7% higher in the oximetry reading.

The smallest difference was in the white group, where the pulse oximeter reading was 3.2% higher than in the gold standard arterial blood gas. A reading of 5.4% higher using pulse oximetry was seen in the Black group and 5.1% higher in the Asian cohort.

The differences between the readings were in the clinically important range of 85 to 89% oxygen saturation, when many clinical decisions are made.

“This data builds on what we know, which is that patients with darker skin have less accurate oxygen measurements using the pulse oximeters. Any error of measurement of oxygen levels will make assessing the severity of COVID-19 infection more difficult, and may delay delivery of timely medical care,” said Andrew Fogarty, from the School of Medicine at Nottingham University, lead author of the study. “We are now exploring the impact of this on clinical outcomes to see if it may have led to any issues in escalating treatment intensity for our patients.”

BerGenBio and the Oslo University Hospital are to test the Norwegian biotech’s cancer drug bemcentinib, in hospitalised COVID-19 patients, as part of the EU-SolidAct trial.

The EU-funded SolidAct is a pan-European programme for setting up rapid and coordinated studies of drugs to treat COVID-19 during the ongoing pandemic, under a master protocol.

As part of the trial, bemcentinib will be studied in up to 500 hospitalised COVID-19 patients, with Bergen-based BerGenBio providing the drug and meeting incremental costs related to the bemcentinib sub-protocol.

The first drug studied under the EU-SolidAct platform was Eli Lilly’s baricitinib, which is now being evaluated by the European Medicines Agency.  Bemcentinib was selected by an international expert group to be the second drug to be studied in EU-SolidAct, which has set up clinical sites in 15 countries.

In cancer, bemcentinib acts to block expression of the enzyme Axl kinase, which is central to a key mechanism by which cancer evades the immune system. The oral, once-a-day, drug is currently in phase II development in a number of cancers.

It was first tested in COVID-19 patients in the UK Accord trial, on the basis of preclinical data showing Axl kinase inhibition blocks viral entry and enhances the interferon response, a key cellular defence mechanism against viral infection.

As the COVID-19 pandemic continues to evolve, it is even more important to identify new therapies for hospitalised patients that have a mechanism of action effective across emerging variants of SARS-CoV-2, said Martin Olin, CEO of BerGenBio. “The EU-SolidAct platform provides BerGenBio with a unique opportunity to rapidly study the effectiveness of bemcentinib and to evaluate the promising signals of efficacy that were observed in hospitalised patients requiring oxygen in earlier studies,” he said.

Marius Trøseid, associate professor at Oslo University Hospital, and chief Investigator of EU-SolidAct agreed. “With new variants and evolving patient populations, it is increasingly important to have more treatment options for preventing need of intensive care and long hospitalisations.”

Since June 2020 researchers at the University of Tours have been working on the development of a nasal vaccine against the SARS-CoV-2 virus.

To date, pre-clinical tests have demonstrated efficacy of the vaccine after two nasal immunisations delivered three weeks apart, both in terms of the immune response and early neutralisation of the original virus and its variants,

These results were subsequently confirmed at the end of 2021 in rodent studies that validated its effectiveness against the Delta variant. The vaccine, consisting of the spike protein and non-mutated viral proteins, is therefore seen as likely to protect against Omicron also.

Now, a start-up LoValTech (for Loire Valley Technology) has been granted an exclusive licence to commercialise the nasal vaccine following its spin out from the university earlier this month.

The company has raised a total of €2.4 million in grants from various funding bodies for further development of the vaccine, including for the production of the vaccine proteins for clinical trials.

LoValTech will also work with collaborators to develop a device for administering the vaccine.

Discussions on the design of the clinical trials and the drafting of the phase I protocol are due to start over the next few weeks.

More than 800 deaths across Europe were avoided as a result of the improved air quality resulting from the government measures taken to limit the spread of the SARS-Cov-2 virus.

Paris, London, Barcelona, and Milan were among the top six cities with the highest number of avoided deaths, according to new research funded by the European Centre for Medium-Range Weather Forecasts on behalf of the Copernicus Atmosphere Monitoring Service and led by a team at the London School of Hygiene & Tropical Medicine (LSHTM).

The study compared government policies from 47 European cities from February to July 2020 and estimated the changes in pollution levels and related number of deaths avoided during the first wave of COVID-19 pandemic.

Measures such as school and workplace closures, cancelling public events, and stay-at-home requirements had the strongest effect on reducing NO2 levels. This is linked to the reduction in road transport and local mobility which is known to be a contributor to NO2 air pollution.

Spanish, French and Italian cities had the largest decrease in NO2, of between 50% and 60% during the period.

Although strong decreases in NO2 were observed, levels of fine particulate matter were reduced more modestly since they are also produced by natural sources, including wildfires and dust, and other emission sources like residential activities, that were slightly increased during lockdown.

“The lockdown during the first wave of the COVID-19 pandemic created immense health and social costs, however, it has offered unique conditions to investigate potential effects of strict policies to reduce pollution levels in urban areas,” said Antonio Gasparrini, professor of biostatistics and epidemiology at LSHTM and senior author of the study. “This ‘natural experiment’ has given us a glimpse of how air quality can be improved by drastic public health measures that would be difficult to implement in normal times. The information can be important to design effective policies to tackle the problem of pollution in our cities.”

Although all cities experienced a slight increase in air pollution levels after the strong decline in March and April 2020, levels remained below business-as-usual scenario estimates throughout the period studied. Restrictions on internal and international travel showed a minor impact on the local pollution levels.

Patients who are receiving immunosuppressive therapy, such as cancer chemotherapy or treatment for rheumatoid arthritis, often do not respond to primary COVID-19 vaccination, and have an increased risk for severe COVID-19 disease.

Until now, it was not clear whether these at risk patients can benefit from an additional booster vaccination.

Now, new research by the Medical University of Vienna has shown that a third vaccination is safe and effective in those patients who were initially unable to produce antibodies after vaccination. The study was recently published in the journal Annals of the Rheumatic Diseases.

Researcher Michael Bonelli was able to show that even patients being treated with the rheumatoid arthritis drug rituximab, who did not respond to primary vaccination are able to develop an immune response following a booster vaccination.

The study is the first randomised, blinded trial to show the efficacy and safety of a booster vaccination in patients without an immune response after two vaccinations because of rituximab treatment.

An ongoing study is investigating the efficacy of a forth vaccination in patients at risk.

Pfizer and BioNtech said they have begun a clinical study of an updated version of their COVID-19 vaccine, which is specifically designed to protect against the Omicron variant.

The study will have three cohorts, comparing the current Pfizer-BioNTech COVID-19 vaccine with the Omicron-based vaccine.

“While current research and real-world data show that boosters continue to provide a high level of protection against severe disease and hospitalisation with Omicron, we recognise the need to be prepared in the event this protection wanes over time and to potentially help address Omicron and new variants in the future,” said Kathrin Jansen, head of vaccine R&D at Pfizer.

“Emerging data indicate vaccine-induced protection against infection and mild to moderate disease wanes more rapidly than was observed with prior strains,” said Ugur Sahin, CEO of BioNTech. “This study is part of our science-based approach to develop a variant-based vaccine that achieves a similar level of protection against Omicron as it did with earlier variants but with longer duration of protection.”

The SARS-CoV-2 Omicron variant causes less severe disease than the Delta variant that went before, even though it is better at escaping immune protection provided by vaccination or previous infections.

The reasons for this have so far remained elusive, but now a new study by scientists at Kent University and the Goethe-University Frankfurt has shown Omicron is particularly sensitive to inhibition by the interferon response, a non-specific immune response that can be triggered by every cell in the body.

They say this explains why COVID-19 patients infected with the Omicron variant are less likely to experience severe disease.

Martin Michaelis of the School of Bioscience at Kent University, said, “Our study provides for the first time an explanation why Omicron infections are less likely to cause severe disease. This is due to [the fact that] Omicron, in contrast to Delta, does not effectively inhibit the host cell interferon immune response.”

Although more transmissible, the study showed Omicron remains sensitive to eight of the most important antiviral drugs and drug candidates for the treatment of COVID-19. The same is not true of monoclonal antibody drugs designed to lock onto and neutralize the virus, which are mostly not effective against the Omicron variant.

The cell culture study the researchers carried out does not exactly reflect the more complex situation in humans, noted Jindrich Cinatl of the Institute of Medical Virology at the Goethe-University, but he said, “Our data provide encouraging evidence that the available antiviral COVID-19 drugs are also effective against Omicron.“