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
Wilkinson, S A J
Richter, Alex
Casey, Anna
Osman, Husam
Mirza, Jeremy D
Stockton, Joanne
Quick, Josh
Ratcliffe, Liz
Sparks, Natalie
Cumley, Nicola
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2022-08-11
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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.
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Wilkinson SAJ, Richter A, Casey A, Osman H, Mirza JD, Stockton J, Quick J, Ratcliffe L, Sparks N, Cumley N, Poplawski R, Nicholls SN, Kele B, Harris K, Peacock TP, Loman NJ. Recurrent SARS-CoV-2 mutations in immunodeficient patients. Virus Evol. 2022 Aug 11;8(2):veac050. doi: 10.1093/ve/veac050
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