SARS-CoV-2 evolution and evasion from multiple antibody treatments in a cancer patient

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients may lead to accelerated viral mutation rate, immune evasion and persistent viral shedding over many months. Here we report the case of a severely immunocompromised cancer patient infected with the Delta variant of SARS-CoV-2 for over 8 months. Genome sequencing of samples taken after repeated monoclonal antibody treatments reveal the emergence and accumulation of mutations enabling escape from neutralization by antibodies. Mutations emerging in accessory and non-structural viral proteins target specific residues of immunomodulatory domains, potentially leading to loss of some functions, while preserving others. The mutated virus managed to completely overcome neutralization by monoclonal antibodies while remaining viable and infective. Our results suggest that the loss of specific immunomodulatory viral functions might confer a selective advantage in immunocompromised hosts. We also compare between mutations emerging in the presence and absence of neutralizing antibodies. Highlights ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the following grants: Horizon 2020 Research and Innovation Framework Programme, PSY\_PGx; The Edmond J. Safra Center for Bioinformatics at Tel Aviv University; The Koret\_UC Berkeley\_Tel Aviv University Initiative in Computational Biology and Bioinformatics; The QBI/UCSF\_Tel Aviv University joint Initiative in Computational Biology and Drug Discovery; Tel Aviv University Richard Eimert Research Fund on Solid Tumors; Collaborative clinical Bioinformatics research of the Edmond J. Safra Center for Bioinformatics and Faculty of Medicine at Tel Aviv University; Israeli Ministry of Science and Technology, Israeli_Russia; Kodesz Institute for Technologies in Healthcare; Tel Aviv University Healthy Longevity Research Center; Tel Aviv University Innovation Laboratories (TILabs). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethics Committee of Shamir Medical Center has approved this study. The relevant patients provided consent for their participation and publication of the study, after being properly informed. Patient Data cannot be shared publicly due to patient confidentiality. All data is available from the Shamir Medical Center Institutional Ethics Committee, contact via Shamir Medical Center (Assaf Harofeh) Helsinki committee by email helsinky@shamir.gov.il for researchers who meet the criteria for access to confidential data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Full sequencing data and reproducible analysis code will be released upon publishing.