Coronavirus Research Tracking - 6 May
Booster vaccine doses, viral and variant evolution, cognitive decline, rapid antigen tests
This week, it’s still not clear which younger age groups may benefit from “booster” mRNA vaccine doses, and T-cell responses may be dependent on vaccine dose.
Most of this week’s papers are non-vaccine related. A review of how the virus has evolved over the last three years, and implications for the future. Several papers look at infection and virulence differences between newer variants and earlier ones. An association between severe Covid and some cognitive declines, and a possible link between gut microbiota and severe Covid. Rapid antigene tests may be most accurate a couple of days after symptoms appear.
The tracker is shared with the COVID-19 Vaccine Media Hub.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Uncertainties about who should get additional vaccine doses
An editorial in the New England Journal of Medicine discusses the difficulties of determining who would benefit from additional vaccine doses. It recommends that the US CDC undertake more work to clarify this. It also recommends improving communications to the public about the limits of vaccine effectiveness.
Prior infections and vaccination provide longer lasting protection against a severe BA.1 infection
Prior infections and vaccinations can provide strong protection from hospitalisation after an BA.1 Omicron infection. In this study, infection-induced protection against Omicron was 81%, increasing to 94% with two, and 97% with three, mRNA vaccine doses. Protection lasted at least 11 months after a prior infection and two vaccine doses.
A prior infection, with or without subsequent vaccination, reduced the risk of an Omicron infection by about 60%. A more severe original infection tended to provide greater protection against a subsequent severe Omicron one. An asymptomatic initial infection reduced the risk of an Omicron infection by about half over the next six months, but then very little protection (without vaccination) was observed.
The study involved over 200,000 test-positive and nearly 500,000 test-negative participants. Asymptomatic infections may have been missed, which could affect the results. The paper has not yet been peer reviewed.
T-cell responses may be proportional to vaccine dose
In experiments using macaques, vaccine dosage did not affect antibody levels but T-cells and antibody effector function increased with dosage. The effector functions provide a link between humoral and cellular control. The study highlights that neutralisation and antibody effector functions are key to stopping viral transmission, while T-cells collaborate with antibody functions to control and clear the virus, so reducing disease severity.
The Johnson & Johnson/Janssen vaccine was used. Only five macaques were vaccinated with each vaccine dose. The paper was published in PLOS Biology.
The biology and evolution of SARS-CoV-2
A review summarises the key points about the biology and evolution of SARS-CoV-2. It notes that while it may evolve to become a seasonal virus with mild symptoms, there is still the potential for it to change its infection and virulence to become a more serious pathogen. The authors note that preparedness for the latter is low. They recommend keeping practices that reduce the risk of infection, improve surveillance measures, and continue developing therapies. The paper was published in Perspectives in Medicine.
STAT News discusses how SARS-CoV-2 may become more like the flu. That is, more predictable and uniform in transmission. This is based on how the current key (sub)-variants of concern (the BA group) are derived from the same cluster, unlike earlier variants.
However, the article also notes that this isn’t the inevitable outcome, and new more transmissible, immune avoiding, and/or pathogenic variants could emerge from other viral lineages.
A BA.2 infection is quite distinct from a BA.1 one
The BA.2 sub-variant is quite distinct virologically from the BA.1 Omicron variant. The effective reproduction number of BA.2 was calculated to be 1.4-fold higher than that of BA.1. BA.2’s spike protein contributes to a higher replication efficacy in cultured human nasal epithelial cells, and makes the virus more efficient at forming cell fusions than the BA.1 spike sequence.
The BA.2 variant is more resistant to antibodies generated by Omicron infections than BA.1. An engineered SARS-CoV-2 virus containing the BA.2 spike protein was also more pathogenic to hamsters than one with the BA.1 spike protein.
Greater pathogenicity of BA.2 compared with BA.1 has not been observed in people, and the authors discuss why the hamster and human results may differ. The use of recombinant viruses may also generate different results than the actual variants. The paper was published in Cell.
BA.4 and BA.5 are more transmissible than BA.1 and BA.2 in South Africa
The BA.4 and BA.5 sub-variants, while somewhat similar to BA.2, have rapidly replaced the former in South Africa, and made up more than 50% of sequenced cases during April. The growth advantage for BA.4 was estimated to be 0.08 per day higher than BA.2 in South Africa, and BA.5 was 0.12.
The growth advantages of these two sub-variants may be due in part to the waning immunity (after about four months) from a previous infection. In other places, the infection risk from BA.4 and BA.5 may be different.
Research is still underway to determine how disease severity and immune escape potential may differ from BA.1 and BA.2 for these two sub-variants. The authors raise the possibility that the BA.4 and BA.5 may have come from chronically infected patients or from an unknown animal reservoir. Further research is required on this point. The paper has not yet been peer reviewed.
BA.2, BA.4 and BA.5 escape antibodies that target BA.1
Another study found that compared to BA.2, the BA.2.12.1, BA.4 and BA.5 sub-lineages had stronger evasion of neutralisation by antibodies. This was observed in serum samples from people who had had three doses of the CoronaVac (Sinovac Biotech) vaccine, and also from those infected with BA.1 and subsequently vaccinated.
This evasion is attributed to a structural change in part of the spike protein, at least in the BA.2 lineage. The authors suggest that exposure to antibodies formed against BA.1 or from vaccines may be responsible for the emergence of BA.2, BA4, and BA 5 sub-lineages. Neutralisation was assessed using pseudoviruses. The paper has not yet been peer reviewed.
Omicron may not be less severe than earlier variants
The severity of Omicron (B.1) may be similar to previous variants, a US study concluded. It took account of comorbidities, demographic differences during each infection wave, and vaccination status. Mortality and hospitalisation risks were similar for Omicron and earlier infection periods.
The study involved 1.3 million patient records. The paper has not yet been peer reviewed.
Cognitive decline after severe Covid
Another study has reported evidence of cognitive decline associated with Covid-19. Decline appears to be more severe and longer lasting if the patient had more severe Covid-19.
Online tests were given to assess accuracy and speed of responses. Those who had had Covid were less accurate and slower in completing the tests than uninfected matched participants. Recovery of cognitive abilities after recovering from Covid-19 was often slow. Cognitive deficits in the Covid patients were about what is expected for normal cognitive decline between the ages of 50 and 70.
However, the pattern of deficits for particular tasks did not match what is seen in normal 50-to-70 year olds. Only 46 patients (average age 51) were involved in the study, with most having severe symptoms. The paper was published in eClinicalMedicine.
Masks potentially could reduce disease severity as well as infection risk
A modelling study indicates that the importance of masks in reducing infection severity may be under appreciated. The model indicates that masks, while not always preventing infection, can reduce the infective dose. This could lead to milder infections while still boosting immunity.
The model is very simple, not taking differences between individuals, or different mask types into account. The authors acknowledge that it is unknown whether mask wearing results in milder symptoms. They also note that control measures cannot rely solely on enforcing mask wearing. The paper was published in Journal of the Royal Society Interface.
Paxlovid pill does not prevent infection
In a Press Release Pfizer reports that a Phase 2/3 trial of the Paxlovid pill is not indicating that it can prevent infection (currently it is approved to treat infections). Participants were given the pill or a placebo daily for five or 10 days. A paper on the study will be published at a later time.
Gut microbes may influence Covid-19 severity
A review article notes how gut microbiota are associated with modulating immune responses, and that disruption of the microbial communities after infection may be associated with more severe Covid-19. It suggests that more attention should be given to manipulating gut microbes as potential Covid-19 therapies. The paper was published in Signal Transduction and Targeted Therapy.
Rapid antigen tests can be more reliable several days after symptoms appear
An assessment of rapid antigen tests found that test sensitivity is highest several days after symptoms appear. RAT results were compared with the results on the same people using PCR tests and viral culturing. The authors recommend that peop;e with possible Covid symptoms should retest one or two days after a negative RAT result.
Compared with a PCR test on the same day the RAT sensitivity was 64%, and 84% when compared with viral culture tests. RAT sensitivity peaked at 77% four days after symptoms developed.
The tests were undertaken on 225 adults and children with confirmed infections. Further research is needed to compare RAT sensitivity in unvaccinated and vaccinated people. The paper was published in JAMA Internal Medicine.