Abstract
Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 19 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients and may be a positive indicator of disease outcome. Clonal expansion of the B cell memory response is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 777 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralising antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand and predict positive patient responses.
Competing Interest Statement
JO, AL, OC, SS, JDG, JD, RM and DKF are employees of Alchemab Therapeutics Limited. RJMB-R is a founder of and consultant to Alchemab Therapeutics Limited. GJK is a consultant to Alchemab Therapeutics Limited. CC is a member of the AstraZeneca External Science Panel and has research grants from Roche, Genentech, AstraZeneca, and Servier that are administered by the University of Cambridge.
