Recurrent SARS-CoV-2 mutations in immunodeficient patients

S. A.J. Wilkinson, Natalie Sparks, Beatrix Kele, Thomas P. Peacock*, Samuel C. Robson, Thomas R. Connor, Nicholas J. Loman*, Tanya Golubchik, Rocio T. Martinez Nunez, David Bonsall, Andrew Rambaut, Luke B. Snell, David K. Jackson, William L. Hamilton, Catherine Moore, Fiona Rogan, Derek J. Fairley, Husam Osman, David A. Simpson, James P. McKennaBen Temperton, Helen Adams, Marc Fuchs, Julia Miskelly, Thomas Davis, Anna Casey, Christopher R. Jones, Stephen Bridgett, Salman Goudarzi, Sophie Jones, Sarah Taylor, Tanya Curran, Ken Smith, Tim Wyatt, Timofey Skvortsov, Declan T. Bradley, Jonathan Moore, Jack C.D. Lee, Zoltan Molnar, Kate Johnson, Leanne J. Murray, Darren R. Murray, Chris Baxter, Deborah Lavin, Arun Mariappan, Clara Radulescu, Aditi Singh, Miao Tang, Kathleen A. Williamson, Carol Scott, The COVID-19 Genomics UK (COG-UK) Consortium

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)
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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.

Original languageEnglish
Number of pages16
JournalVirus Evolution
Volume8
Issue number2
DOIs
Publication statusPublished - 11 Aug 2022

Bibliographical note

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.

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press.

Keywords

  • convergent evolution
  • genomics
  • immunodeficiency
  • persistent infection
  • SARS-CoV-2
  • variant emergence

ASJC Scopus subject areas

  • Microbiology
  • Virology

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