Deep mining of early antibody response in COVID-19 patients yields potent neutralisers and reveals high level of convergence

Passive immunisation using monoclonal antibodies will play a vital role in the fight against COVID-19. Until now, the majority of anti-SARS-CoV-2 antibody discovery efforts have relied on screening B cells of patients in the convalescent phase. Here, we describe deep-mining of the antibody repertoires of hospitalised COVID-19 patients using a combination of phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralising antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded potent neutralising antibodies with distinct mechanisms of action, including the identification of a novel non-ACE2 receptor blocking antibody that is not expected to be affected by any of the major viral variants reported. The study highlighted the presence of potent neutralising antibodies with near germline sequences within both the IgG and IgM pools at early stages of infection. Furthermore, we highlight a highly convergent antibody response with the same sequences occurring both within this study group and also within the responses described in previously published anti-SARS-CoV-2 studies.