PT - JOURNAL ARTICLE AU - Georgia Bullen AU - Jacob D. Galson AU - Pedro Villar AU - Lien Moreels AU - Line Ledsgaard AU - Giada Mattiuzzo AU - Gareth Hall AU - Emma M. Bentley AU - Edward W. Masters AU - David Tang AU - Sophie Millett AU - Danielle Tongue AU - Richard Brown AU - Ioannis Diamantopoulos AU - Kothai Parthiban AU - Claire Tebbutt AU - Rachael Leah AU - Krishna Chaitanya AU - Deividas Pazeraitis AU - Sachin B. Surade AU - Omodele Ashiru AU - Lucia Crippa AU - Richard Cowan AU - Matthew W. Bowler AU - Jamie I. Campbell AU - Wing-Yiu Jason Lee AU - Mark D. Carr AU - David Matthews AU - Paul Pfeffer AU - Simon E. Hufton AU - Kovilen Sawmynaden AU - Jane Osbourn AU - John McCafferty AU - Aneesh Karatt-Vellatt TI - Deep mining of early antibody response in COVID-19 patients yields potent neutralisers and reveals high level of convergence AID - 10.1101/2020.12.29.424711 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.12.29.424711 4099 - http://biorxiv.org/content/early/2020/12/29/2020.12.29.424711.short 4100 - http://biorxiv.org/content/early/2020/12/29/2020.12.29.424711.full AB - 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.Competing Interest StatementThe authors have declared no competing interest.