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Recurrent SARS-CoV-2 Mutations in Immunodeficient Patients
Sam AJ Wilkinson; Alex Richter; Anna Casey; Husam Osman; Jeremy D Mirza; Joanne Stockton; Josh Quick; Liz Ratcliffe; Natalie Sparks; Nicola Cumley; Radoslaw Poplawski; Sam Nicholls; Beatrix Kele; Kathryn Harris; - The COVID-19 Genomics UK (COG-UK) consortium; Thomas P Peacock; Nicholas J Loman.
  • Sam AJ Wilkinson; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, UK, B15 2TT
  • Alex Richter; Institute of Immunology and Immunotherapy (III), College of Medical and Dental Sciences, University of Birmingham, UK, B15 2TT
  • Anna Casey; Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, UK, B15 2TH.
  • Husam Osman; Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, UK, B15 2TH.
  • Jeremy D Mirza; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, UK, B15 2TT
  • Joanne Stockton; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, UK, B15 2TT
  • Josh Quick; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, UK, B15 2TT
  • Liz Ratcliffe; Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, UK, B15 2TH.
  • Natalie Sparks; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, UK, B15 2TT
  • Nicola Cumley; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, UK, B15 2TT
  • Radoslaw Poplawski; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, UK, B15 2TT
  • Sam Nicholls; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, UK, B15 2TT
  • Beatrix Kele; Virology Department, NHS East and South East London Pathology Partnership, Royal London Hospital, Barts Health NHS Trust, UK, EC1A 7BE.
  • Kathryn Harris; Virology Department, NHS East and South East London Pathology Partnership, Royal London Hospital, Barts Health NHS Trust, UK, EC1A 7BE.
  • - The COVID-19 Genomics UK (COG-UK) consortium; https://www.cogconsortium.uk - Full list of consortium names and affiliations are in the appendix
  • Thomas P Peacock; Department of Infectious Disease, Imperial College London, London, UK, W2 1PG
  • Nicholas J Loman; Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, UK, B15 2TT
Preprint in English | medRxiv | ID: ppmedrxiv-22271697
ABSTRACT
Long-term 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 COG-UK dataset. The spike gene receptor binding domain (RBD) and N-terminal domains (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 most recurrent frequently 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 which aid intra-host transmission or persistence which are often different to mutations which 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.
Full text: Available Collection: Preprints Database: medRxiv Language: English Year: 2022 Document Type: Preprint

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Full text: Available Collection: Preprints Database: medRxiv Language: English Year: 2022 Document Type: Preprint