Coronavirus Research Tracking - Non-vaccine Edition - 20 May
long covid, hepatitis risks, new therapies and diagnostic tests, estimating health costs
This week, a mild infection in unvaccinated people may not protect against later infections, several papers on long Covid, hepatitis and blood clot risks after infections, a potential new anti-viral therapy, and new diagnostic tests.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Tentative signs that South Africa’s fifth wave is starting to slow
There is an indication that the fifth infection wave in South Africa, involving BA.4 & BA.5 may be flattening, and the infection rate is slowing. The information was presented on Twitter.
Comparing BA.1 and BA.2 infectivity & pathogenicity
In mice and hamsters the BA.1 and BA.2 variants have similar infectivity and pathogenicity. Both were less pathogenic than previous variants. Plasma from COVID-19 convalescent individuals and vaccinated people showed much lower neutralising activity against BA.2 than the Delta and wild-type variants.
BA.2 had limited infectivity of the lungs of mice and hamsters. It isn’t yet known if that is the case in humans too. Several monoclonal antibodies and other therapeutics were able to reduce BA.2’s ability to infect lungs. The paper was published in Nature.
Mild infections in unvaccinated people may lead to re-infection a year later
Unvaccinated people with relatively mild Covid-19 infections may be vulnerable to new infections a year later. Most people who had mild Covid-19 infections had a much reduced ability to neutralise variants of concern and also had low T cell responses.
Covid-19 severity was determined using US National Institute of Health guidelines. T cell functionality only examined cytokine production. The study involved laboratory assays rather than actual infection rates in unvaccinated populations. Forty three people were involved in the study. The paper was published in Cell Reports Medicine.
A review in Nature Medicine describes what is known about post-acute infection syndromes, both for Covid-19 and myalgic encephalomyelitis/chronic fatigue syndrome. There are at least four hypotheses for these syndromes. Considerably more research is needed to better understand the causes and potential treatment options.
A US analysis of healthcare claims found that three quarters of claims for long Covid had not been hospitalised with Covid-19. The analysis uses a new standard code in the US for long Covid, and 78,000 claims were examined. Adults between 36 and 50, and females, were the most likely to make a long Covid claim.
The most common co-occurring symptoms in claims were abnormalities of breathing (23.2% of patients with post-COVID conditions), cough (18.9%) and malaise and fatigue (16.7%). Different age groups could have different co-occurring symptoms.
The data are based on privately insured patients, so may not be representative of the general US population. The paper has not yet been peer reviewed.
An earlier Spanish study, published in Scientific Reports, found that just over half of people with long Covid symptoms had been hospitalised with Covid-19.
High antibody levels may be associated with severe Covid-19
A small study found that high antibody levels were associated with more severe Covid-19. Severity was based on chest radiography scores, and the need for supplemental oxygen. Maximum radiography score correlated with maximum antibody titre, but antibody levels peaked after chest scores, so the authors conclude that antibody levels are the result of clinical conditions.
Only 40 patients were involved in the study, and 13 had severe or critical symptoms. The paper was published in the Journal of Microbiology, Immunology and Infection.
Hepatitis risk in children after Covid-19
A short note published in The Lancet Gastroenterology and Hepatology proposes that recent cases of severe acute hepatitis in children could be due to an adenovirus infection where there is also a persistent SARS-CoV-2 infection in the gastrointestinal tract. This could lead to superantigen-mediated immune activation. They propose testing stool samples for SARS-CoV-2 in children with severe acute hepatitis.
Another study found a possible link with higher liver enzyme levels. Children under 10 appear to be at greater risk of having elevated levels of liver enzymes after having Covid-19, compared with other respiratory diseases. This may contribute to an increased risk of developing hepatitis. There was a 2.5-fold increase in risk of higher levels of two liver enzymes in sera, and a 3-fold increase in elevated bilirubin between one and six months after infection. Further research is required to see if these elevated levels result in an increased risk of hepatitis. The paper has not yet been peer reviewed.
1% of Covid-19 cases may have thromboembolisms
A European study found that venous thromboembolism or arterial thromboembolism occurred in up to 1% of Covid cases. The risk increased with patient age and being hospitalised. Men were more likely to develop thromboembolisms than women. Risk of death was about four times higher for those with a Covid-related embolism when they were not hospitalised, and around two-fold higher when already hospitalised. The paper was published in The Lancet Infectious Diseases.
Two monoclonal antibodies made in plants were found to be able to neutralise wild-type and Delta variants. Producing antibodies in plants can be cheaper than making them in animal cells.
When one of the antibodies was included in a cocktail with animal cell-produced antibodies there was a synergistic effect on neutralising activity. That is, the neutralising effect was greater than that for the individual antibodies. Further research is required on plant-produced antibodies. The paper was published in Vaccines.
Viral resurgence after Paxlovid not due to resistance or antibody response
Examination of a patient who had a resurgence of Covid-19 symptoms after taking Paxlovid ruled out drug resistance and insufficient neutralising antibodies. The authors suggest that the Paxlovid dose was possibly too low. Three other people in the family were also infected at the same time but did not have a resurgence after taking Paxlovid. The time of starting Paxlovid treatment relative to symptom onset wasn’t stated (see last week’s Tracker). The paper has not yet been peer reviewed.
A broad-spectrum antiviral shows early promise
Inhibitors of viral cell entry were found to provide broad-spectrum protection against a range of viruses, including SARS-CoV-2 variants. Other viruses inhibited included HIV, Zika virus, respiratory syncytial virus, and seasonal coronaviruses.
Intranasal administration reduces RSV and SARS-CoV-2 levels in the lungs of mice. Research on other animals is underway. The paper was published in Advanced Science.
A urine test for a previous infection
Antibodies against SARS-CoV-2 can be detected in urine, potentially offering an easy test for infection. Detection has about 90% sensitivity and 100% specificity. Test accuracy was highest about 20 days after noticeable symptoms, and accuracy was similar to serum tests.
The study involved 139 infected participants (including those with mild and more severe symptoms). Asymptomatic people were not included. The test targeted the N-terminal protein, so could be used to distinguish a prior infection from those who had received vaccines only containing the spike protein. The paper was published in Science Advances.
FDA approve PCR test to screen for three respiratory viruses
The FDA has given emergency use approval to a PCR test that detects SARS-CoV-2, flu and respiratory syncytial virus (RSV). The sample can be taken at home and then sent to a lab. It is called the Labcorp Seasonal Respiratory Virus RT-PCR DTC Test.
Modelling infection risk in a room
A model of a 50 m2 room found that infection risk after 10 minutes can increase from 1 to 50% when viral RNA concentration increases from 2x10^8 RNA copies/mL to 2x10^10. Above a concentration of 10^10, more of the larger airborne droplets will carry viral particles, so the risk of infection can approach 100%.
The model accounts for several factors that influence infection risk For example, the infected subject's mode of emission, droplet characteristics, indoor environment parameters (air humidity, ventilation, and turbulence), and protection factors (mask, air cleaners).
Increasing ventilation reduced the risk, while relative humidity had little effect on infection risk. The paper has not yet been peer reviewed.
Estimating the health costs of Covid
A news article in Nature, discusses the difficulty in estimating the health cost of the pandemic. Different countries calculate the costs of death and disability differently, and there is variability in the data collected and reliability. The impact of long Covid can also not yet be factored in.