Coronavirus Research Tracking - 27 August - Non-vaccine edition

Infectiousness, therapies, clinical care, ventilation, masks, & origins

This week due to the number of interesting papers, vaccine and non-vaccine related research have been split into separate tracking reports, and distributed separately.

The non-vaccine related papers include peak infectious periods, Delta variant mutations, monoclonal antibody pre-clinical trials, a convalescent sera clinical trial, improved hospital care, classroom ventilation, mask effectiveness, and viral origins

The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.

Non-vaccine-related papers

Most transmission probably occurs within a 5 day period

A Chinese study indicates that transmission is most likely 2 days before and 3 days after symptom onset. Asymptomatic cases were less likely to infect others, and if they did those people too tended to be asymptomatic. This was based on 730 index cases and nearly 9,000 contacts between January and July. Information on what variants were involved was not reported. The paper was published in JAMA Internal Medicine.

Delta mutations

A news article in Nature discusses the P681R spike protein mutation that appears to be a major factor in Delta’s greater transmissibility. This is based on findings in a paper not yet peer reviewed. The Nature article highlights that other mutations will also play a role in higher transmissibility.

Another paper suggests that it is possible that the Delta variant could acquire several other mutations that enable it to become even more infectious and able to avoid vaccine protection. Experiments introduced four mutations from the spike protein N-terminal domain in other variants into a pseudovirus with the Delta variant spike protein sequence. This was able to evade neutralisation by some sera from Pfizer/BioNTech vaccinated people, and enhanced infectivity in cell culture tests. 

When the pseudovirus was introduced into mice there was also variability in how effective mice vaccinated with the wild type spike protein neutralised the variant. Further research is required to understand the results, but the paper indicates the need for on-going vaccine development in case more infectious and/or resistant variants emerge. The paper has not yet been peer reviewed.

Regeneron’s monoclonal antibody therapy approved in the UK

The UK medicines regulator has approved Ronapreve (also known as REGEN-COV), Regeneron’s two monoclonal antibody treatment for severe Covid-19. It has emergency use approval in several countries. The price for the drug in the UK has not been stated, but, in line with other monoclonal antibody therapies, is likely to be expensive and used for only the most vulnerable people.

Other monoclonal antibodies continue to show promise in pre-clinical trials

Six monoclonal antibodies were found to effectively neutralise the Alpha and Beta variants in cell-based tests. Three were tested on mice. All gave very good protection in mice (based on weight loss and death) that had been infected with a wild type strain or the Alpha variant, while one also provided protection against the Beta variant. The paper was published in Cell Reports.

A monoclonal antibody identified by infecting mice was protective against several current variants of concern. Effectiveness was determined by how much weight the infected mice lost. The antibody targets conserved parts of the spike protein. The authors note that effectiveness of the antibody still needs to be tested on primates and people. A cocktail of antibodies is also preferred, to reduce the risks of the virus developing resistance. The paper was published in Immunity.

Convalescent plasma does not appear to help control severe Covid-19

A randomised controlled clinical trial found that convalescent plasma does not limit disease progression in high risk patients. The plasma was given to 257 patients within one week of symptom onset. There may be other benefits from convalescent plasma but they were not examined in this trial. The paper was published in The New England Journal of Medicine

Pre-existing auto-antibodies may be associated with severe Covid-19

Auto-antibodies that neutralise type I interferons are more common in elderly (over 70) people. Type I interferons are an early response to infections and can limit viral reproduction. Overall, 20% of patients over 80 with severe Covid-19 and patients of any age who died from it had the auto-antibodies, indicating they may be a factor in some cases of severe Covid-19. The paper was published in Science Immunology

Keeping patients with severe Covid-19 flat improves their recovery chances

A randomised controlled trial found that keeping Covid-19 patients with respiratory failure in an “awake prone position” reduces the need to intubate them. A control group received standard hospital care, which did not involve prolonged prone positioning. When assessed at day 28 the incidence of intubation in the awake prone group was significantly lower than in the control group. The paper was published in The Lancet Respiratory Medicine.

Lower reported Covid-19 morbidity in Africa may be partly due to younger populations

Relatively low Covid-19 morbidity and mortality in sub-Saharan Africa (except South Africa) is attributed largely to the younger populations in those countries. Other factors also play a role. Under-diagnosis may also contribute to lower numbers of reported cases. The paper also notes that stringent lockdowns in many African countries are likely to have severe social and economic impacts and should be applied with caution. The paper was published in Global Health: Science and Practice.

Classroom ventilation risks

A Swiss study of viral levels in schools found that a combination of natural ventilation, surgical face masks and the use of HEPA filters would be very effective at reducing aerosol transmission in classes. The paper has not yet been peer reviewed

A US study found that in classrooms aerosols are unlikely to be evenly distributed. Body heat in relatively cold rooms generate thermals that affect air flows and prevent or slow mixing.

It identified that open windows directing air horizontally at face height may increase the risk of infection. Cold air flowing down a closed window next to which an infected student is sitting may also increase infection risk. The researchers propose how these risks can be reduced. The paper was published in Building and Environment.

Measuring mask effectiveness

Cloth and surgical masks have much poorer filtration efficiencies (10% and 12%, respectively) than R95 (60%) and KN95 (46%) masks. In lab tests cloth and surgical masks resulted in higher aerosol concentrations within 2 metres of the subject. Mask fit is also an important factor influencing dispersion. Still, the research demonstrated that even simple masks provide some suppression of aerosols. Buildup of aerosols was measured over 10 hours, so the research did not simulate normal conditions.

While these findings aren’t surprising, the research was more comprehensive than many earlier studies, The paper was published in Physics of Fluids.

Evidence on viral origin

A review of the origins of SARS-CoV-2, originally included as a pre-print in the 9 July Tracker, has now been published in Cell. It’s key conclusion, that a zoonotic origin is the most likely origin, has not changed.

A comment in Nature from members of the WHO team investigating the virus’ origin notes the window of opportunity to investigate a lab-leak origin is quickly closing. It identifies six research priorities for phase 2 of the investigation, and encourages the scientific community (and political leaders) to work together to investigate them.

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