Coronavirus Research Tracking - 11 September
Russian vaccine, Covid-19 in children, correlates for disease severity, and Icelandic antibodies
In this week’s Research Tracker the main focus is on infection and disease in children, with other papers on disease and mortality risks.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Russian vaccine Phase 1 & 2 trial data published, but faces scientific challenge
Results from the “Sputnik-V” vaccine, based on two inactivated adenoviruses, have been published in The Lancet. The trials, involving 18 to 40 participants, compared frozen and freeze-dried formulations of the vaccine. No serious adverse effects were reported, and the vaccinations stimulated antibody and T cell responses.
However, some scientists have concerns that some of the data in the paper seems too similar. The Lancet has invited the vaccine paper’s authors to respond.
An article in Nature Reviews Drug Discovery provides an overview of the, now 321 & counting, vaccine candidates. It is still too early to assess the potential of those in clinical trials. The authors point out that most vaccines against respiratory illnesses target reducing disease severity rather than preventing infection.
Improving understanding of Multisystem Inflammatory Syndrome in Children
A review of studies reporting cases of Multisystem Inflammatory Syndrome in Children (MIS-C) found that 71% of 662 children with the condition had to spend time in intensive care units and 11 died. The long term outcomes of those who recover have yet to be studied. The review was published in EClinicalMedicine.
Two independent papers report that MIS-C is more severe in children infected with Covid-19, and is distinct from acute Covid-19 and Kawasaki disease.
The paper in Nature Medicine suggests that altered interferon responses &/or antibody-dependent enhancement in children with Covid-19 may lead to the development of MIS-C.
The paper in Cell finds that autoantibodies may be a causal factor in MIS-C.
Five reasons why children may be less likely to develop severe Covid-19
On a more upbeat note, a paper in the Proceedings of the National Academy of Sciences describes the five genetic and physiological factors that may explain why children tend not to develop serious Covid-19 conditions.
Children with Covid-19 hospitalized at same rate as children with the ‘flu
A paper in JAMA Open Network reports that the hospitalisation rates of children with Covid-19 and influenza in the US were the same (about 20%), as were admission rates to intensive care units. However children hospitalised with Covid-19 were generally older, and more likely to have an underlying health condition than those in hospital with influenza.
Children can be less likely to be infected …
A study of 33,000 children in US hospitals found that infection with SARS-CoV-2 was low. Only 250 (0.65%) tested positive. The research was published in JAMA Pediatrics.
… and may not show typical Covid-19 symptoms
A smaller Korean study, also in JAMA Pediatrics, noted the greater difficulty in detecting infections in children. It found that 22% of 91 infected children were asymptomatic, while two thirds had unrecognised symptoms before diagnosis. Only 8.5% were diagnosed with Covid-19 at the time of symptom onset.
Viral loads correlate with disease severity
A paper in PLoS Biology reports that more severe disease in adults is associated with higher levels of viral infection, at least in nasopharyngeal samples. The paper also demonstrates that, compared to women with Covid-19, men have different transcription patterns for several genes. This may lead to reduced antiviral responses in men, and so more severe outcomes.
The study confirmed that, like SARS-CoV infections, the response to infection is characterised by increased type I and II Interferon production.
The virus suppresses type I Interferons
However, research published in Cell Reports finds that SARS-CoV-2 is more effective at suppressing the expression of type I Interferons than SARS-CoV, helping it impede the control of viral replication. This is due to a mutation in the ORF3b gene that creates a shortened gene transcript that acts as an interferon antagonist.
The researchers also found a natural mutation in ORF3b in two patients which created a much longer transcript. This appears to be even more effective at suppressing interferon. Whether this leads to more severe disease requires further study.
Risk scores for mortality
A study, involving nearly sixty thousand patients in the UK, has developed a method to rank the risk of mortality. It is based on 8 variables that can be measured when Covid-19 patients are admitted to hospital. The method performed better, or was simpler, than 15 existing clinical tools, and can help clinicians quickly assign appropriate care. It is described in The British Medical Journal.
Antibodies in Iceland
A study tested over 30,000 Icelanders for antibodies to SARS-CoV-2. The researchers estimated that about 0.9% of its 364,000 residents had been infected. Testing a smaller group of Icelanders they found that some antibodies were still present up to 4 months after diagnosis. The research was published in the New England Journal of Medicine.