eprintid: 10144209 rev_number: 14 eprint_status: archive userid: 699 dir: disk0/10/14/42/09 datestamp: 2022-02-25 09:10:57 lastmod: 2022-07-01 16:08:16 status_changed: 2022-02-25 09:10:57 type: article metadata_visibility: show sword_depositor: 699 creators_name: Astbury, Stuart creators_name: Reynolds, Catherine J creators_name: Butler, David K creators_name: Munoz-Sandoval, Diana C creators_name: Lin, Kai-Min creators_name: Pieper, Franziska P creators_name: Otter, Ashley creators_name: Kouraki, Afroditi creators_name: Cusin, Lola creators_name: Nightingale, Jessica creators_name: Vijay, Amrita creators_name: Craxford, Simon creators_name: Aithal, Guruprasad P creators_name: Tighe, Patrick J creators_name: Gibbons, Joseph M creators_name: Pade, Corinna creators_name: Joy, George creators_name: Maini, Mala creators_name: Chain, Benny creators_name: Semper, Amanda creators_name: Brooks, Timothy creators_name: Ollivere, Benjamin J creators_name: McKnight, Áine creators_name: Noursadeghi, Mahdad creators_name: Treibel, Thomas A creators_name: Manisty, Charlotte creators_name: Moon, James C creators_name: COVIDsortium investigators, . creators_name: Valdes, Ana M creators_name: Boyton, Rosemary J creators_name: Altmann, Daniel M title: HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19 ispublished: pub divisions: C10 divisions: D15 divisions: B02 divisions: UCL keywords: COVID-19, HLA, SARS-CoV-2, T cell immunity, immunogenetics, vaccine note: © 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/). 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. date: 2022-05 date_type: published publisher: Wiley official_url: https://doi.org/10.1111/imm.13450 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1940449 doi: 10.1111/imm.13450 medium: Print-Electronic lyricists_name: Chain, Benjamin lyricists_id: BMCHA43 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Immunology volume: 166 number: 1 pagerange: 68-77 event_location: England citation: 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 <#> 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; COVIDsortium investigators, .; Valdes, Ana M; Boyton, Rosemary J; Altmann, Daniel M; - view fewer <#> (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 <https://doi.org/10.1111/imm.13450>. Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10144209/1/Bhuva_HLA-DR%20polymorphism%20in%20SARS-CoV-2%20infection%20and%20susceptibility%20to%20symptomatic%20COVID-19_VoR.pdf