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HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19

Astbury, Stuart; Reynolds, Catherine J; Butler, David K; Munoz-Sandoval, Diana C; Lin, Kai-Min; Pieper, Franziska P; Otter, Ashley; ... Altmann, Daniel M; + view all (2022) HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19. Immunology , 166 (1) pp. 68-77. 10.1111/imm.13450. Green open access

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Abstract

SARS-CoV-2 infection results in different outcomes ranging from asymptomatic infection, to mild or severe disease and death. Reasons for this diversity of outcome include differences in challenge dose, age, gender, comorbidity and host genomic variation. Human leukocyte antigen (HLA) polymorphisms may influence immune response and disease outcome. We investigated the association of HLAII alleles with case definition symptomatic COVID-19, virus-specific antibody and T cell immunity. 1,364 UK healthcare workers (HCW) were recruited during the first U.K. SARS-CoV-2 wave and analyzed longitudinally, encompassing regular PCR screening for infection, symptom reporting, imputation of HLAII genotype and analysis for antibody and T cell responses to nucleoprotein (N) and spike (S). Of 272 (20%) HCW who seroconverted, the presence of HLA-DRB1*13:02 was associated with a 6.7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*15:02 was associated with lower nucleocapsid T cell responses. There was no association between DRB1 alleles and anti-spike antibody titres after two COVID vaccine doses. However, HLA DRB1*15:01 was associated with increased spike T cell responses following both first and second dose vaccination. Trial registration - NCT04318314 and ISRCTN15677965.

Type: Article
Title: HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/imm.13450
Publisher version: https://doi.org/10.1111/imm.13450
Language: English
Additional information: © 2022 The Authors. Immunology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: COVID-19, HLA, SARS-CoV-2, T cell immunity, immunogenetics, vaccine
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10144209
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