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Recurrent SARS-CoV-2 mutations in immunodeficient patients

S A J Wilkinson, Alex Richter, Anna Casey, Husam Osman, Jeremy D Mirza, Joanne Stockton, Josh Quick, Liz Ratcliffe, Natalie Sparks, Nicola Cumley, Radoslaw Poplawski, Samuel N Nicholls, Beatrix Kele, Kathryn Harris, Thomas P Peacock, Nicholas J Loman, Ronan Lyons Orcid Logo

Virus Evolution, Volume: 8, Issue: 2

Swansea University Author: Ronan Lyons Orcid Logo

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DOI (Published version): 10.1093/ve/veac050

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 s...

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Published in: Virus Evolution
ISSN: 2057-1577
Published: Oxford University Press (OUP) 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa66441
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spelling v2 66441 2024-05-15 Recurrent SARS-CoV-2 mutations in immunodeficient patients 83efcf2a9dfcf8b55586999d3d152ac6 0000-0001-5225-000X Ronan Lyons Ronan Lyons true false 2024-05-15 MEDS 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. Journal Article Virus Evolution 8 2 Oxford University Press (OUP) 2057-1577 SARS-CoV-2, genomics, variant emergence, persistent infection, immunodeficiency, convergent evolution 12 8 2022 2022-08-12 10.1093/ve/veac050 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee COG-UK is supported by funding from the Medical Research Coun-cil (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. 2024-06-19T16:50:40.2403379 2024-05-15T10:38:45.9943456 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Health Data Science S A J Wilkinson 1 Alex Richter 2 Anna Casey 3 Husam Osman 4 Jeremy D Mirza 5 Joanne Stockton 6 Josh Quick 7 Liz Ratcliffe 8 Natalie Sparks 9 Nicola Cumley 10 Radoslaw Poplawski 11 Samuel N Nicholls 12 Beatrix Kele 13 Kathryn Harris 14 Thomas P Peacock 15 Nicholas J Loman 16 Ronan Lyons 0000-0001-5225-000X 17 66441__30378__1e176412b69646b68a6dcf95dcb36cf2.pdf 66441.pdf 2024-05-15T10:42:26.2327042 Output 2088001 application/pdf Version of Record true This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License. true eng http://creativecommons.org/licenses/by-nc/4.0/
title Recurrent SARS-CoV-2 mutations in immunodeficient patients
spellingShingle Recurrent SARS-CoV-2 mutations in immunodeficient patients
Ronan Lyons
title_short Recurrent SARS-CoV-2 mutations in immunodeficient patients
title_full Recurrent SARS-CoV-2 mutations in immunodeficient patients
title_fullStr Recurrent SARS-CoV-2 mutations in immunodeficient patients
title_full_unstemmed Recurrent SARS-CoV-2 mutations in immunodeficient patients
title_sort Recurrent SARS-CoV-2 mutations in immunodeficient patients
author_id_str_mv 83efcf2a9dfcf8b55586999d3d152ac6
author_id_fullname_str_mv 83efcf2a9dfcf8b55586999d3d152ac6_***_Ronan Lyons
author Ronan Lyons
author2 S A J Wilkinson
Alex Richter
Anna Casey
Husam Osman
Jeremy D Mirza
Joanne Stockton
Josh Quick
Liz Ratcliffe
Natalie Sparks
Nicola Cumley
Radoslaw Poplawski
Samuel N Nicholls
Beatrix Kele
Kathryn Harris
Thomas P Peacock
Nicholas J Loman
Ronan Lyons
format Journal article
container_title Virus Evolution
container_volume 8
container_issue 2
publishDate 2022
institution Swansea University
issn 2057-1577
doi_str_mv 10.1093/ve/veac050
publisher Oxford University Press (OUP)
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Health Data Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Health Data Science
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description 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.
published_date 2022-08-12T16:50:39Z
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