Coronavirus Research Tracking - 24 June
Immune evasion, long Covid, multiple infections, infection risks, ventilation
This week, more papers confirming the immune evasion of Omicron sub-variants, and the prevalence of long Covid in adults. For children, long Covid can be harder to diagnose, due to similarities with other common ailments. A study describes the cumulative health risks that can occur from multiple infections, and there is evidence that normal speech may pose a higher transmission risk than previously thought. The need to improve indoor ventilation is emphasised in a UK report.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Neutralisation of Omicron sub-variants
Neutralising antibody levels were 6-to-21 fold lower against Omicron variants than the wild-type virus after a third Pfizer/BioNTech dose. Escape from neutralisation was greatest for the BA.2.12.1, BA.4, and BA.5 sub-variants.
Neutralisation activity against BA.4 and BA.5 was also lower after a BA.1 or BA.2 infection, compared with activity against wild type and BA.1 and BA.2 sub-variants. The paper was published in the New England Journal of Medicine.
More results from Moderna Omicron vaccine trial
A press release from Moderna says that their Omicron-based booster vaccine increased neutralising antibody titres against BA.4/BA.5 sub-variants 5.4-fold. This was still 3-fold lower than activity against the BA.1 sub-variant.
Distinctiveness of the viral receptor binding domain provides a good indication of vaccine effectiveness
The distinctiveness of the virus receptor binding domain from the vaccine version is a good predictor of vaccine effectiveness, a study has shown. The more distinct the viral variant, the less effective the vaccine is against symptomatic infection.
For mRNA vaccines, effectiveness against the Delta variant (based on a range of studies) was estimated to be 82.8%. For Omicron sub-lineages effectiveness ranged from 11.9% (BA.2) to 33.3% (BA.1). Effectiveness was calculated shortly after the second dose.
The effect of a prior infection was not assessed. The paper was published in Nature Medicine.
Covid severity associated with some specific comorbidities
A study reports that pre-existing chronic kidney disease and obesity are associated with an increased risk of developing severe Covid. Those with kidney disease had nearly an 8-fold higher risk than those without, and obese patients were 3 times more likely to develop severe Covid than non-obese patients. The authors note that the kidneys help filter out cytokines from the blood, so probably reduce inflammation risks.
Unlike previous studies, heart disease and chronic obstructive pulmonary disease were not associated with a greater risk of severe Covid. However, different comorbidities (and clusters of comorbidities) were found to affect the immune system in different ways.
The study is based on infections from the second half of 2020. The numbers of patients with some specific sets of comorbidities were small, which can affect some conclusions. The paper was published in the Journal of Allergy and Clinical Immunology.
Cumulative health risks from multiple infections
Additional Covid infections, even after vaccination, can add to the health risks created by an earlier infection. Compared to a single infection group, those with subsequent SARS-CoV-2 infections had 2-to-3-fold higher risks of hospitalisation, mortality, and developing specific persistent conditions. Risks increased as the number of infections increased.
The study is based on the health records of a large number of US Veterans Affairs patients, so the results may not be applicable to the general population. The paper has not yet been peer reviewed.
Long Covid prevalence in adults
The UK Office of National Statistics estimated that 3% of the population may have persistent Covid-19 symptoms. Fatigue was the most common persistent symptom. Seventy percent of those with long Covid said the symptoms affected their daily activities.
Persistent symptoms were more frequently reported by those aged 35 to 69 years, females, people living in more deprived areas, those working in social care, teaching and education or health care, and those with another activity-limiting health condition or disability. Symptoms were self-reported.
A review of other studies estimated that women were 22% more likely than men to develop persistent Covid symptoms. The risk of developing different specific persistent conditions varied. Women were nearly 2.3-times more likely to develop persistent ear, nose & throat conditions than men. Gastrointestinal and psychiatric/mood symptoms were also more common in women with long Covid. Endocrine and renal disorders were more likely to occur in men than women following an infection.
The authors note that social and cultural factors which increase the risk of exposure in women (such as nursing and aged care work) may play a role alongside biological differences between the sexes. The studies included in the review were often relatively small, and few studies specifically looked at sex differences, so further research is necessary. The paper was published in Current Medical Research and Opinion.
Long Covid in children
A Danish study found that persistent symptoms can occur in both previously infected and uninfected children under 14, but they tended to be more common in those who had had Covid. Some long Covid symptoms are common ailments in children.
For children aged 0-to-3, 40% of Covid cases had at least one symptom two months after an infection, compared with 27% in uninfected controls (. In 4-to-11 year olds, prevalence was 38% and 34%, respectively. In 12-to-14 year olds, prevalence was 46% vs 41%.
Children between 4 and 14 who had had Covid had better quality of life scores than similar children who were uninfected. This could be due to a variety of factors, such as a better awareness of infection, and so being less scared.
The study collected information using a survey to mothers, and occurred during the Alpha and Delta waves. Responses for over 40,000 children were received. The paper was published in The Lancet Child & Adolescent Health.
Long Covid risk from Omicron
The risk of developing long Covid after an Omicron infection may be up to half as low as for the Delta variant. In this study all participants had been vaccinated, with time since vaccination having little effect. The risk of long Covid after Omicron was slightly lower for those over 65 than for younger adults.
However, many more people have been infected with the Omicron variant than the Delta, so there will be more cases of long Covid from the Omicron infection wave. The study involved self-reporting of symptoms and their persistence. The paper was published in The Lancet.
Persistence of viral RNA
A study found that SARS-CoV-2 can persist in some people for up to a year. The spike protein was detectable in 60% of patients with persistent symptoms, suggesting reservoirs of the virus. The protein was not found in previously infected people who did not develop long Covid. Other SARS-CoV-2 proteins were also sometimes detected in those with persistent symptoms.
Other studies have found that the spike protein from vaccines is not detectable after a few weeks, so the protein could be used as a biomarker for long Covid. The study was based on 63 people who had been infected, with 37 diagnosed with long Covid. The paper has not yet been peer reviewed.
Indoor ventilation needs to be improved
The Royal Academy of Engineering has published a social cost benefit analysis of the infection resilience of building environments in the UK. It estimated that the annual discounted expected cost of influenza type infections (pandemic and seasonal) is about £23 billion (or 1% of GDP in 2020). Over half the infections (56%) come from schools, hospitals and local community buildings.
Introducing better ventilation (≥10 litres/second/person) is expected to reduce long range aerosol transmission by about 50%. This may also lead to small improvements in productivity. Improved ventilation could generate £3 billion in benefits annually, through reduced sickness.
An opinion published in the BMJ emphasises that now is not the time to give up on controlling transmission. Wearing of N95 and similar masks provides short term control measures. Longer-term measures that do not rely on human behaviour are also advocated. This includes improving indoor ventilation, which will not only reduce the risk of SARS-CoV-2 infection, but other airborne diseases too.
Seasonal pattern to infections in the northern hemisphere
Analysis of infection patterns in western Europe and the US suggest that SARS-CoV-2 has a seasonal infection pattern, peaking in winter. The authors recommend giving annual booster vaccine doses just before winter. The paper has not yet been peer reviewed.
Transmission risk from normal speech may be greater that previously thought
Speech-generated aerosols may be more important in spreading the coronavirus than previously thought, if infected people are not coughing or sneezing. This study provided a more accurate measurement of the number and size of aerosols produced during normal speech and breathing.
It found large numbers of intermediate-sized particles (5- to 20-μm) were produced when speaking, and these can remain in the air for minutes. There were twice as many of these particles as smaller ones, which have previously been assumed to be the main aerosol type associated with infection.
The study didn’t test for the presence of viral particles in the aerosols. The paper was published in Proceedings of the National Academy of Sciences.
Chronic infections generate a range of mutants
A Nature news article discusses the importance of studying viral variants in people with chronic infections. Sequencing of these variants sometimes identifies sequences that look like intermediate steps towards known variants of concern. This supports the hypothesis that long term infections can generate a broad variety of mutations, a very few of which could lead to future variants of concern.
Similar conclusions were made in a study of 27 patients with chronic infections. Resurgence of the infection was associated with antibody evasion mutations. Some of these mutations are found in variants of concern, but they usually lack other mutations that enhance transmission. There was also considerable genetic diversity in viral genomes in the patients. The paper was published in Nature Medicine.
Detecting infection early with a wearable device
A wearable device normally used to monitor fertility cycles was able to detect a SARS-CoV-2 infection in the pre-symptomatic phase. When measured during sleep significant changes in respiratory rate, heart rate & heart rate variability, and wrist skin temperature were associated with an infection. A machine learning algorithm was able to detect 68% of positive cases two days before symptom onset.
The test was done on a relatively small number of adults, but a 20,000 person randomised trial is now underway. The paper was published in BMJ Open.