There will be two Research Tracker’s this week, catching up on developments over the last fortnight. Today’s focus is on recent reports about the UK, South African and Brazilian viral variants. Friday’s regular issue will cover other topics.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Genetic and epidemiological information on the variants
Genetic sequence and epidemiological information on new variants are being curated at the Cov-Lineages website. B.1.1.7 from the UK, B.1.351 (or 501Y.V2) from South Africa, and the Brazilian P.1.
New variants may challenge some existing tests
The US Food and Drug Administration has warned that new SARS-CoV-2 variants may lead to false negative results for some virus tests. This means that a test does not detect the virus when it is in the sample. This can be due to the mutations eliminating specific recognition sites for the test.
The FDA provide several recommendations on how to reduce the risk of this, such as using several different tests, or tests that target several parts of the virus.
Is P.1 evading the immune system?
A news item in Science highlights concerns about the Brazilian “P.1” variant. Unlike the UK and South African variants it may be better at evading the immune system, rather than (just) being more transmissible. It appears to have emerged in part of the Amazon where there are already high levels of infection, and presumably high levels of existing immunity.
However, immune system evasion hasn’t yet been proven, and some researchers suggest that increased transmissibility should be the main worry for the moment.
The news item includes WHO comments that caution against just focusing on viral variation. Human behaviours are also important factors that influence infection risks. It also quotes a researcher warning not to focus on individual mutations in the virus, but to investigate how groups of different mutations influence transmissibility and immune responses.
Pfizer vaccine may remain effective against some new variants
An example of a focus on a single mutation is a draft paper (not yet peer reviewed) testing the Pfizer/BioNTech vaccine. Sera from 20 people who received the Pfizer/BioNTech vaccine were tested to see if antibodies neutralised SARS-CoV-2 that differed only at position 501 in the spike protein (a mutation the UK, South African and several other variants share). The study found that vaccine-generated antibodies were able to equally neutralise SARS-CoV-2 both viral variants.
However, the study didn’t test vaccine effectiveness against the actual new variants (which have several other mutations), just viral constructs with that particular single variation. STATnews discusses this paper in more detail. Further research is required to understand the impacts of multiple mutations.
In the previous Research Tracker we included a study that demonstrated mutations at position 484 in the spike protein can reduce antibody binding.
UK variant doesn’t seem to have evaded natural or vaccine-induced immune responses
A preliminary study (not yet peer reviewed) of the UK variant suggests that the mutations it has would not enable it to evade the immune system response in most infected people. The authors also consider that there is no evidence that current vaccines will be less effective against this variant.
Experimental study of the impact of mutations on immune system evasion
Other research (pre-print paper) used laboratory experiments to investigate what mutations in the spike protein could reduce neutralisation by antibodies. Fifty mutants resulted in reduced neutralisation by 19 monoclonal antibodies. Some of the mutations were able to evade several antibodies, and different antibodies led to mutations at the same amino acid sites.
Tests with Covid-19 patient sera indicate that those who produce a more limited range of antibodies may be more likely to generate virus mutants that escape antibody neutralisation.
An observational study of viral evolution
A paper, from early December, published in the New England Journal of Medicine studied how SARS-CoV-2 evolved over 154 days in an immunocompromised patient who eventually died. Amino acid changes were mostly in the spike protein, despite this region making up only 13% of the genome. This suggests that relatively strong selection pressures are acting on the spike protein.
Experimental study of the impact of mutations on transmissibility
Another study (also not yet peer-reviewed) examined selection of viral mutations that result in stronger binding to the ACE2 receptor, and so potentially leading to more infectious viral variants. It found mutations that are seen in the UK and South African variants to bind more strongly, supporting the hypothesis of greater transmissibility. Continued laboratory selection resulted in a 600-fold increase in binding affinity, so more infectious variants may emerge if the pandemic is not quickly controlled.