Recurrent SARS-CoV-2 mutations in immunodeficient patients

Wilkinson, S. A. J., Richter, Alex, Casey, Anna, Osman, Husam, Mirza, Jeremy D., Stockton, Joanne, Quick, Josh, Ratcliffe, Liz, Sparks, Natalie, Cumley, Nicola, Poplawski, Radoslaw, Nicholls, Samuel N., Kele, Beatrix, Peacock, Thomas P. and Loman, Nicholas J. and The COVID-19 Genomics UK (COG-UK) Consortium (2022) Recurrent SARS-CoV-2 mutations in immunodeficient patients. Virus Evolution, 8 (2). ISSN 2057-1577

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Abstract

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation.There is an apparent selective pressure for mutations that aid cell–cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.

Item Type:	Article
Additional Information:	Funding Information: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) [grant code: MC_PC_19027], and Genome Research Limited, operating as the Wellcome Sanger Institute.
Uncontrolled Keywords:	convergent evolution,genomics,immunodeficiency,persistent infection,sars-cov-2,variant emergence,microbiology,virology ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	01 Nov 2024 11:30
Last Modified:	12 Nov 2024 13:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/97411
DOI:	10.1093/ve/veac050

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