HLA‐DR polymorphism in SARS‐CoV‐2 infection and susceptibility to symptomatic COVID‐19. Issue 1 (8th March 2022)

• Record Type: Journal Article
• Authors: Astbury, Stuart; Reynolds, Catherine J.; Butler, David K.; Muñoz‐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.
• Other Names: Abbass Hakam investigator.; Abiodun Aderonke investigator.; Alfarih Mashael investigator.; Alldis Zoe investigator.; Altmann Daniel M. investigator.; Amin Oliver E. investigator.; Andiapen Mervyn investigator.; Artico Jessica investigator.; Augusto João B. investigator.; Baca Georgiana L. investigator.; Bailey Sasha N. L. investigator.; Bhuva Anish N. investigator.; Boulter Alex investigator.; Bowles Ruth investigator.; Boyton Rosemary J. investigator.; Bracken Olivia V. investigator.; O'Brien Ben investigator.; Brooks Tim investigator.; Bullock Natalie investigator.; Butler David K. investigator.; Captur Gabriella investigator.; Champion Nicola investigator.; Chan Carmen investigator.; Chandran Aneesh investigator.; Collier David investigator.; de Sousa Jorge Couto investigator.; Couto‐Parada Xose investigator.; Cutino‐Moguel Teresa investigator.; Davies Rhodri H. investigator.; Douglas Brooke investigator.; Genova Cecilia investigator.; Dieobi‐Anene Keenan investigator.; Diniz Mariana O. investigator.; Ellis Anaya investigator.; Feehan Karen investigator.; Finlay Malcolm investigator.; Fontana Marianna investigator.; Forooghi Nasim investigator.; Gaier Celia investigator.; Gibbons Joseph M. investigator.; Gilroy Derek investigator.; Hamblin Matt investigator.; Harker Gabrielle investigator.; Hewson Jacqueline investigator.; Hickling Lauren M. investigator.; Hingorani Aroon D. investigator.; Howes Lee investigator.; Hughes Alun investigator.; Hughes Gemma investigator.; Hughes Rebecca investigator.; Itua Ivie investigator.; Jardim Victor investigator.; Lee Wing‐Yiu Jason investigator.; Jensen Melaniepetra investigator.; Jones Jessica investigator.; Jones Meleri investigator.; Joy George investigator.; Kapil Vikas investigator.; Kurdi Hibba investigator.; Lambourne Jonathan investigator.; Lin Kai‐Min investigator.; Louth Sarah investigator.; Maini Mala K. investigator.; Mandadapu Vineela investigator.; Manisty Charlotte investigator.; McKnight Áine investigator.; Menacho Katia investigator.; Mfuko Celina investigator.; Mitchelmore Oliver investigator.; Moon Christopher investigator.; Moon James C. investigator.; Muñoz‐Sandoval Diana C. investigator.; Murray Sam M. investigator.; Noursadeghi Mahdad investigator.; Otter Ashley investigator.; Pade Corinna investigator.; Palma Susana investigator.; Parker Ruth investigator.; Patel Kush investigator.; Pawarova Babita investigator.; Petersen Steffen E. investigator.; Piniera Brian investigator.; Pieper Franziska P. investigator.; Pope Daniel investigator.; Prossora Mary investigator.; Rannigan Lisa investigator.; Rapala Alicja investigator.; Reynolds Catherine J. investigator.; Richards Amy investigator.; Robathan Matthew investigator.; Rosenheim Joshua investigator.; Sambile Genine investigator.; Schmidt Nathalie M. investigator.; Semper Amanda investigator.; Seraphim Andreas investigator.; Simion Mihaela investigator.; Smit Angelique investigator.; Sugimoto Michelle investigator.; Swadling Leo investigator.; Taylor Stephen investigator.; Temperton Nigel investigator.; Thomas Stephen investigator.; Thornton George D. investigator.; Treibel Thomas A. investigator.; Tucker Art investigator.; Veerapen Jessry investigator.; Vijayakumar Mohit investigator.; Welch Sophie investigator.; Wodehouse Theresa investigator.; Wynne Lucinda investigator.; Zahedi Dan investigator.; Altmann Daniel M investigator.; Boyton Rosemary J. investigator.; Brooks Tim investigator.; Chain Benjamin investigator.; Maini Mala K. investigator.; Manisty Charlotte investigator.; McKnight Áine investigator.; Moon James C. investigator.; Noursadeghi Mahdad investigator.; Treibel Thomas A. investigator.; Aithal Guruprasad P. investigator.; Ashraf Waheed investigator.; Astbury Stuart investigator.; Ball Jonathan K. investigator.; Chappell Joseph G. investigator.; Craxford Simon investigator.; Cusin Lola M. L. investigator.; Duncan Joshua D. investigator.; Ikram Adeel investigator.; Irving William L. investigator.; Jackson Hannah J. investigator.; Kelly Anthony investigator.; Lingaya Melanie investigator.; Marson Ben A. investigator.; Newham Jayne investigator.; Nightingale Jessica investigator.; Norrish Alan investigator.; Nowicka Barbara investigator.; Ollivere Benjamin J. investigator.; Tarr Alexander W. investigator.; Tighe Patrick J. investigator.; Tsoleridis Theocharis investigator.; Urbanowicz Richard A. investigator.; Valdes Ana M. investigator.; Vijay Amrita investigator.;
• Is Part Of: Immunology. Volume 166:Issue 1(2022)
• Page Start: 68
• Page End: 77
• Publication Date: 2022-03-08
• Subjects: COVID‐19 -- HLA -- immunogenetics -- SARS‐CoV‐2 -- T‐cell immunity -- vaccine; Immunology -- Periodicals
• DOI: 10.1111/imm.13450
• Languages: English
• ISSNs: 0019-2805

Abstract

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. Abstract : SARS‐CoV‐2 infection results in different outcomes ranging from asymptomatic infection, to mild or severe disease and death. We investigated the association of HLAII alleles with case definition symptomatic COVID‐19, virus‐specific antibody and T cell immunity. Presence of HLA‐DRB1*13:02 was associated with increased risk of symptomatic COVID‐19, while, after vaccination, HLA DRB1*15:01 was associated with increased spike T cell responses.