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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; Kouraki, Afroditi; Cusin, Lola; Nightingale, Jessica; Vijay, Amrita; Craxford, Simon; Aithal, Guruprasad P; Tighe, Patrick J; Gibbons, Joseph M; Pade, Corinna; Joy, George; Maini, Mala; Chain, Benny; Semper, Amanda; Brooks, Timothy; Ollivere, Benjamin J; McKnight, Áine; Noursadeghi, Mahdad; Treibel, Thomas A; Manisty, Charlotte; Moon, James C; Valdes, Ana M; Boyton, Rosemary J; Altmann, Daniel M

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Catherine J Reynolds

David K Butler

Diana C Munoz-Sandoval

Kai-Min Lin

Franziska P Pieper

Ashley Otter

Afroditi Kouraki

Lola Cusin

Jessica Nightingale

Simon Craxford

Professor of Molecular Immunology

Joseph M Gibbons

Corinna Pade

George Joy

Mala Maini

Benny Chain

Amanda Semper

Timothy Brooks

Áine McKnight

Mahdad Noursadeghi

Thomas A Treibel

Charlotte Manisty

James C Moon

Rosemary J Boyton

Daniel M Altmann


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.


Astbury, S., Reynolds, C. J., Butler, D. K., Munoz-Sandoval, D. C., Lin, K., Pieper, F. P., …Altmann, D. M. (2022). HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19. Immunology, 166(1), 68-77.

Journal Article Type Article
Acceptance Date Jan 28, 2022
Online Publication Date Mar 14, 2022
Publication Date May 1, 2022
Deposit Date Feb 1, 2022
Publicly Available Date Mar 15, 2023
Journal Immunology
Print ISSN 0019-2805
Electronic ISSN 1365-2567
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 166
Issue 1
Pages 68-77
Keywords COVID-19; SARS-CoV-2; immunogenetics; HLA; vaccine; T cell immunity
Public URL
Publisher URL
Additional Information Authors on behalf of the COVIDsortium Investigators


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