February 28, 2021

expert reaction to up to six cases of the Brazilian Manaus P.1 variant of concern having been detected in the UK

It’s been announced that the Manaus P.1 variant of concern has been detected in up to 6 people in the UK.

Prof Lawrence Young, Professor of Molecular Oncology, Warwick Medical School, said:

“The virus variant from Brazil (P.1 or 501Y.V3) has changes in the spike protein which make it more infectious and more resistant to the immune response.  This variant has 3 mutations at key sites in the receptor binding domain (K417T, E484K and N501Y) of the spike gene.  Two of these (E484K and N501Y) are within the receptor-binding motif (RBM), the main functional motif that forms the interface with the human ACE2 receptor.  The N501Y mutation is the same as that found in the UK virus variant which is now widespread here and around the world.  The E484K mutation appears to provide some escape from immune recognition – it prevents virus infection from being completely blocked by certain monoclonal antibodies and by the antibodies induced  by certain vaccines.  There is no indication that this virus variants is associated with more severe disease.

“Recent reports from Manaus in Brazil, where the P1 variant is fuelling a surge in infections, suggest that this variant is responsible for re-infecting individuals who were previously infected with a different variant of the virus.  That’s why it’s even more important to do everything to stop the spread of this virus and all other variants including strict border controls and an efficient test, trace and isolate system.

“It was thought that a second wave of infection in Manaus was impossible because of the scale of the original outbreak in March/April 2020 which resulted in high levels of protective immunity – estimated at up to 66% of the population (https://www.medrxiv.org/content/10.1101/2020.09.16.20194787v1).  It is likely that the P1 variant is driving the current surge in infected cases due to re-infection as a consequence of both waning antibody responses and the P1 variant’s ability to evade antibodies induced from previous infection with a different variant.  The possibility of re-infection has been documented in a few cases in Brazil including one study where the P1 virus was responsible for the second infection (https://virological.org/t/sars-cov-2-reinfection-by-the-new-variant-of-concern-voc-p-1-in-amazonas-brazil/596) and other cases where re-infection was due to a different variant [P2] (https://wwwnc.cdc.gov/eid/article/27/5/21-0191_article) which also contains the E484K mutation.”

Prof Nick Loman, Professor of Microbial Genomics and Bioinformatics, Institute of Microbiology and Infection, University of Birmingham, said:

Why is this a variant of concern?

“P.1, described in January by the CADDE project (https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586), carries several mutations that are seen in other variants of concern that are predicted to change the behaviour of the virus.  These include E484K, which is predicted to make existing antibodies to SARS-CoV-2 less effective, as well as N501Y which is potentially linked to increase transmissibility.  P.1 is associated with a surge of cases in Manaus (in the Amazonas region of Brazil) late last year which experienced a second severe wave of COVID-19.  This was concerning as it raises the possibility it is able more easily re-infect patients due to the mutations it carries.  However the evidence for this is currently limited.

Do we know if it’s more transmissible than the dominant variant in the UK?

“We don’t currently know if this variant is more transmissible than B.1.1.7, the variant that is currently dominant in the UK.

Is it a surprise that it’s been detected here?

“It’s possibly somewhat surprising we haven’t seen it to date as it has been associated with high case numbers in Brazil, and has been detected in several other countries including Belgium, Italy and Switzerland as tracked by the CovLineages site (https://cov-lineages.org/global_report_P.1.html).  This recent set of cases in the UK will need rapid epidemiological investigations to establish if there are further linked cases.”

https://www.gov.uk/government/news/confirmed-cases-of-covid-19-variants-identified-in-uk

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