Coronavirus Research Tracking - 4 June
Renaming variants, vaccine effectiveness, T cell responses, blood clot cause, phylogenetic and infection dynamics, party experiment, other mRNA vaccines
This week a revision of variant names, vaccine effectiveness against the Delta variant and adolescents, the importance of studying T cell and tissue immune responses, variant evolution and dynamics, why some vaccines may cause blood clots, testing mask effectiveness at a concert, and future mRNA vaccines.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
New names for variants
The WHO has developed new names for variants of concern to make it easier for non-scientists to remember, and avoid stigmatising a particular region. The names for current variants of concern are:
Alpha - B.1.1.7
Beta - B.1.351
Gamma - P.1
Delta - B.1.617.2
They have also renamed variants of interest.
Vaccines still help against the Delta variant
Monoclonal antibodies and sera from convalescent and vaccinated people were 3- to 6-fold less potent against Delta (B.1.617.2), compared with the Alpha (B.1.1.7) variant. This is similar to the response seen for the Beta (B.1.351) variant. The Delta variant has nine distinctive spike protein mutations.
Two doses of the Pfizer/BioNTech vaccine provided a large boost in neutralisation activity. One dose of the AstraZeneca/Oxford vaccine did not result in a strong neutralisation response against Delta, or the Beta variant. The paper has not yet been peer reviewed.
CoronaVac effective against some variants
The CoronaVac vaccine from Sinovac Biotech, is able to neutralise variants that lack the E484K mutation. Its neutralisation ability was lower for variants with this mutation (such as Beta, Gamma, and B.1.526). The tests were performed using pseudoviruses. The paper was published in The Lancet Infectious Diseases.
Pfizer/BioNTech vaccine safe for adolescents
A clinical trial demonstrated that the Pfizer/BioNTech vaccine was safe and effective for 12-15 year olds. Eleven hundred adolescents received two doses of the vaccine and had no serious adverse reactions. None of the vaccinated participants developed Covid-19 symptoms seven days after the second dose, while 16 who received a placebo did. The study did not assess asymptomatic infections. It was published in the New England Journal of Medicine.
Another spike mutation of interest
The P681R mutation in the B.1.617 lineage has been shown to make it easier to cut the spike protein, leading to more efficient infection. The researchers suggest that this makes this lineage potentially more transmissible. The Delta (B.1.617.2) variant is known to be more transmissible. The Alpha (B.1.1.7) variant has a P681H mutation, which may also contribute to its higher level of transmissibility. The paper has not yet been peer reviewed.
Increasing attention given to T cell responses to variants
While the Beta (B.1.351) variant induces lower antibody responses, T cell responses against it appear to be unaffected. There was robust production of CD4+ T cells from both convalescent patients and people who had received one dose of the Pfizer/BioNTech. The authors suggest that the strong T cell response may account for the lower incidence of severe disease in most who become infected a second time or after vaccination. Only 20 people were involved in the study, so further research is required to confirm the responses. The paper was published in Science Immunology.
The changing spectrum of Covid variants
A review of variants describes the changing types of mutations, and their effects, being seen in the spike protein of the SARS-CoV-2 virus. It notes the greater ability of some variants to escape some immune control, but the need for further research to understand the real world consequences. The paper was published in Nature Reviews Microbiology.
The dynamics of England’s peak infection period
A detailed analysis of the spread of Covid-19 in the UK between September 2020 and April 2021 illustrates the effects of different lockdowns, and the waxing and waning of different variants. Many sub-epidemics of different viral lineages contributed to the peak infection in October.
It also describes that while the E484K mutation has often been associated with greater transmissibility, that is not always the case. In some variants the E484K mutation potentially creates a disadvantage. And the rapidly spreading Delta (B.1.617.2) variant does not have E484K. The paper has not yet been peer reviewed.
A possible explanation for vaccine-related blood clots
A research team proposed an explanation for why clotting events are sometimes seen with adenovirus vector vaccines and not with the mRNA vaccines. The AstraZeneca/Oxford and Johnson & Johnson/Janssen vaccines use inactivated adenoviruses to introduce the spike protein into cells. During transcription of the spike protein, after cell entry, shortened variants of the protein appear to be produced. These are soluble and, the authors propose, may interact with antibodies and cause clots under specific conditions.
The Johnson & Johnson vaccine produces fewer variants than the AstraZeneca vaccine, and so, according to the authors, may explain why clots appear to be slightly less frequent for the J&J vaccine. mRNA vaccines do not generate these alternative transcripts. The adenovirus vaccines could be redesigned to avoid the formation of shortened spike proteins. The paper has not yet been peer reviewed.
Different immune responses in blood and tissues
A commentary in Nature emphasises the different immune cell profiles in the blood and tissues of patients with Covid-19, and that the most critical immune responses occur in tissue rather than the blood. However, studies of immune cells in tissues lag far behind those from blood. The author emphasises the need to systematically collect paired blood and tissue samples from patients, and to improve researcher and clinician collaborations so a better picture of immune responses can be developed.
Estimating global variation in SARS-CoV-2
A paper, published in the Proceedings of the National Academy of Sciences, highlights the importance of estimating the number of SARS-CoV-2 virions (viral particles) present in the population. It estimates that infections may lead to between one and 100 billion viral particles in and infected person at the peak of infection. However, this would still only represent a very small percentage of cells in the airway and lungs being infected, and far outnumbered by antibodies. Infections are also characterised by substantial variations in viral loads between individuals, tissues, and at different times during infection.
Based on the number of viral particles and mutation rate, the authors estimate that a very high level of genetic diversity is present across the world at any one time. However, despite the frequent regeneration of individual mutations, many of these will not persist due to a variety of factors which restrict mutations from being passed on. The authors conclude by identifying knowledge gaps about infection processes and dynamics that their calculations uncover.
Party on with masks on
An experiment in Barcelona reports that attending a well ventilated indoor music concert while wearing an N95 mask does not increase the risk of becoming infected with SARS-CoV-2. Adults who tested negative with a rapid antigen test were randomly assigned to either attending the concert or to go home. Eight days later the participants were tested using both the rapid antigen and PCR tests.
Two out of 495 of the non-concert goers tested positive, compared with none out of 465 who attended the concert, suggesting that some potentially risky social activities, with conditions, could start again. The effect of having infectious people attend the concert was not tested. The paper was published in The Lancet Infectious Diseases.
Frequent recombination between bat coronaviruses
A phylogenetic analysis of bat viruses related to SARS-CoV-2 identified the frequent nature of recombination between them. This makes identification of immediate ancestors more difficult. The authors note that the overlapping ranges of the bat hosts in Southern China and Southeast Asia provides many opportunities for interspecies transmission and recombination, which could explain the emergence of SARS-CoV-2.
The authors conclude that further sampling of bats in southern China, and wildlife transported to markets, is necessary not just to clarify the origin of SARS-CoV-2, but to also detect other potential zoonotic coronavirus events. The paper has not yet been peer reviewed.
The expanding world of mRNA vaccines
A news item in Nature Medicine discusses how mRNA vaccines are now being developed for other diseases. It reports that BioNTech has developed a genetic “toolbox” that allows them to control how much, for how long, and where a protein in the vaccine is expressed. Better influenza vaccines are being developed, as well as ones for HIV, hepatitis C, malaria, dengue, and tuberculosis. Vaccines against cancer are also being explored.