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Characterization of B-cell receptor clonality and immunoglobulin gene usage at multiple time points during active SARS-CoV-2 infection
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  • Robert J. Kreitman,
  • Evgeny Arons,
  • Kiersten Henry,
  • Christopher Haas,
  • Mory Gould,
  • Jack Tsintolas,
  • Jack Mauter,
  • Hong Zhou,
  • Peter Burbelo,
  • Jeffrey Cohen
Robert J. Kreitman
National Cancer Institute Laboratory of Molecular Biology

Corresponding Author:kreitmar@mail.nih.gov

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Evgeny Arons
National Cancer Institute Laboratory of Molecular Biology
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Kiersten Henry
MedStar Montgomery Medical Center
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Christopher Haas
MedStar Franklin Square Medical Center
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Mory Gould
National Cancer Institute Laboratory of Molecular Biology
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Jack Tsintolas
National Cancer Institute Laboratory of Molecular Biology
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Jack Mauter
National Cancer Institute Laboratory of Molecular Biology
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Hong Zhou
National Cancer Institute Laboratory of Molecular Biology
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Peter Burbelo
National Institute of Dental and Craniofacial Research
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Jeffrey Cohen
National Institute of Allergy and Infectious Diseases Laboratory of Infectious Diseases
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Abstract

Purpose Although monoclonal antibodies specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are known, information about the B-cell receptor (BCR) repertoire and its change in patients during COVID-19 disease progression is underreported. Methods We used immunoglobulin heavy chain (IGH) variable region (IGHV) spectratyping and next-generation sequencing of peripheral blood B-cell genomic DNA collected at multiple time points during disease evolution to study B-cell response to SARS-CoV-2 infection in 14 individuals with acute COVID-19. Results We found a broad distribution of responding B-cell clones. The IGH gene usage was not significantly skewed but frequencies of individual IGH genes changed repeatedly. We found predominant usage of unmutated and low mutation-loaded IGHV rearrangements characterizing naïve and extrafollicular B-cells among the majority of expanded peripheral B-cell clonal lineages at most tested time points in most patients. IGH rearrangement usage showed no apparent relation to anti-SARS-CoV-2 antibody titers. Some patients demonstrated mono/oligoclonal populations carrying highly mutated IGHV rearrangements indicating antigen experience at some of the time points tested, including even before anti-SARS-CoV-2 antibodies were detected. Conclusion We present evidence demonstrating that the B-cell response to SARS-CoV-2 is individual and includes different lineages of B-cells at various time points during COVID-19 progression.
09 Aug 2023Submitted to Journal of Medical Virology
09 Aug 2023Submission Checks Completed
09 Aug 2023Assigned to Editor
09 Aug 2023Review(s) Completed, Editorial Evaluation Pending
09 Aug 2023Reviewer(s) Assigned
03 Sep 2023Editorial Decision: Revise Minor
30 Sep 20231st Revision Received
06 Oct 2023Review(s) Completed, Editorial Evaluation Pending
06 Oct 2023Submission Checks Completed
06 Oct 2023Assigned to Editor
06 Oct 2023Editorial Decision: Accept