Recurrent SARS-CoV-2 mutations in immunodeficient patients

The COVID-19 Genomics UK (COG-UK) Consortium, 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, Rich Livett, Catherine Ludden, Sally Corden, Eleni Nastouli, Gaia Nebbia, Ian Johnston, Katrina LythgoeM. Estee Torok, Ian G. Goodfellow, Jacqui A. Prieto, Kordo Saeed, David K. Jackson, Catherine Houlihan, Dan Frampton, William L. Hamilton, Adam A. Witney, Giselda Bucca, Cassie F. Pope, Catherine Moore, Emma C. Thomson, Ewan M. Harrison, Colin P. Smith, Fiona Rogan, Shaun M. Beckwith, Abigail Murray, Dawn Singleton, Darren L. Smith, Matthew Bashton, Gregory R. Young, Clare M. McCann, Andrew Nelson, Matthew R. Crown, Chris Williams, Rachel J. Williams, John H. Henderson, Wen C. Yew, Hannah Jones, John A. Hartley

*Corresponding author for this work

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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
Article numberveac050
JournalVirus Evolution
Volume8
Issue number2
Early online date11 Aug 2022
DOIs
Publication statusPublished - 12 Aug 2022

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