HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19
Author(s)
Type
Journal Article
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. A total of 1364 UK healthcare workers (HCWs) were recruited during the first UK SARS-CoV-2 wave and analysed 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.
Date Issued
2022-03-08
Date Acceptance
2022-01-28
Citation
Immunology, 2022, 166 (1), pp.68-77
ISSN
0019-2805
Publisher
Wiley
Start Page
68
End Page
77
Journal / Book Title
Immunology
Volume
166
Issue
1
Copyright Statement
© 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, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000766016000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
MR/W020610/1
MR/S019553/1
MR/V036939/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
COVID-19
HLA
immunogenetics
SARS-CoV-2
T-cell immunity
vaccine
HEPATITIS-B
POSITION-86
ASSOCIATION
DIMORPHISM
PEPTIDES
HLA-DR13
Publication Status
Published
Date Publish Online
2022-02-14