Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.12.18.21267628; this version posted December 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . RESISTANCE CONFERRING MUTATIONS IN SARS-CoV-2 DELTA FOLLOWING SOTROVIMAB INFUSION Rebecca J Rockett1,4*, Kerri Basile2, Susan Maddocks2,3, Winkie Fong1, Jessica E Agius1, Jessica Johnson Mackinnon1,4, Alicia Arnott1,2, Shona Chandra1, Mailie Gall1,2, Jenny Draper1,2, Elena Martinez1,2, Eby M Sim1,2, Clement Lee2, Christine Ngo2, Marc Ramsperger2, Andrew N Ginn2,4, Qinning Wang1,2, Michael Fennell2, Danny Ko2, H Ling Lim2,5, Nicky Gilroy3, Matthew V N O’Sullivan1,2,3,4, Sharon C-A Chen1,2,4, Jen Kok1,2, Dominic E Dwyer1,2,4, Vitali Sintchenko1,2,4* 1 Centre for Infectious Diseases and Microbiology-Public Health, Westmead Hospital, Westmead, New South Wales, Australia 2 Centre for Infectious Diseases and Microbiology Laboratory Services, New South Wales Health Pathology, Institute for Clinical Pathology and Medical Research, Westmead, New South Wales, Australia 3 Department of Infectious Diseases, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia 4 Sydney Institute of Infectious Diseases, University of Sydney, Sydney, New South Wales, Australia 5 Parramatta Public Health Unit, Western Sydney Local Health District, Parramatta, New South Wales, Australia *Corresponding authors Dr Rebecca J. Rockett and Prof Vitali Sintchenko rebecca.rockett@health.nsw.gov.au and Vitali.Sintchenko@health.nsw.gov.au Sydney Institute of Infectious Diseases, University of Sydney, Sydney, New South Wales, Australia NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.12.18.21267628; this version posted December 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . ABSTRACT (100 words) Several Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralising monoclonal antibodies (mAbs) have received emergency use authorisation by regulatory agencies for treatment and prevention of Coronavirus Disease 2019 (COVID-19), including in patients at risk for progression to severe disease. Here we report the persistence of viable SARS-CoV-2 in patients treated with sotrovimab and the rapid development of spike gene mutations that have been shown to confer high level resistance to sotrovimab in vitro. We highlight the need for SARS-CoV-2 genomic surveillance in at risk individuals to inform stewardship of mAbs use and prevent potential treatment failures. medRxiv preprint doi: https://doi.org/10.1101/2021.12.18.21267628; this version posted December 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license .