PMID- 35156709 OWN - NLM STAT- MEDLINE DCOM- 20220419 LR - 20240320 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 166 IP - 1 DP - 2022 May TI - HLA-DR polymorphism in SARS-CoV-2 infection and susceptibility to symptomatic COVID-19. PG - 68-77 LID - 10.1111/imm.13450 [doi] AB - 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. CI - (c) 2022 The Authors. Immunology published by John Wiley & Sons Ltd. FAU - Astbury, Stuart AU - Astbury S AD - NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK. AD - Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK. FAU - Reynolds, Catherine J AU - Reynolds CJ AD - Department of Infectious Disease, Imperial College London, London, UK. FAU - Butler, David K AU - Butler DK AD - Department of Infectious Disease, Imperial College London, London, UK. FAU - Munoz-Sandoval, Diana C AU - Munoz-Sandoval DC AD - Department of Infectious Disease, Imperial College London, London, UK. FAU - Lin, Kai-Min AU - Lin KM AD - Department of Infectious Disease, Imperial College London, London, UK. FAU - Pieper, Franziska P AU - Pieper FP AD - Department of Infectious Disease, Imperial College London, London, UK. FAU - Otter, Ashley AU - Otter A AUID- ORCID: 0000-0002-8317-9194 AD - National Infection Service, Public Health England, Porton Down, UK. FAU - Kouraki, Afroditi AU - Kouraki A AD - Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK. FAU - Cusin, Lola AU - Cusin L AD - School of Life Sciences, University of Nottingham, Nottingham, UK. FAU - Nightingale, Jessica AU - Nightingale J AD - Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK. FAU - Vijay, Amrita AU - Vijay A AD - Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK. FAU - Craxford, Simon AU - Craxford S AD - Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK. FAU - Aithal, Guruprasad P AU - Aithal GP AD - NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK. AD - Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK. FAU - Tighe, Patrick J AU - Tighe PJ AD - School of Life Sciences, University of Nottingham, Nottingham, UK. FAU - Gibbons, Joseph M AU - Gibbons JM AD - Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK. FAU - Pade, Corinna AU - Pade C AD - Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK. FAU - Joy, George AU - Joy G AD - Barts Heart Centre, St. Bartholomew's Hospital, London, UK. FAU - Maini, Mala AU - Maini M AD - Division of Infection and Immunity, University College London, London, UK. FAU - Chain, Benny AU - Chain B AD - Division of Infection and Immunity, University College London, London, UK. FAU - Semper, Amanda AU - Semper A AD - National Infection Service, Public Health England, Porton Down, UK. FAU - Brooks, Timothy AU - Brooks T AD - National Infection Service, Public Health England, Porton Down, UK. FAU - Ollivere, Benjamin J AU - Ollivere BJ AD - Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK. FAU - McKnight, Aine AU - McKnight A AD - Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK. FAU - Noursadeghi, Mahdad AU - Noursadeghi M AD - Division of Infection and Immunity, University College London, London, UK. FAU - Treibel, Thomas A AU - Treibel TA AD - Barts Heart Centre, St. Bartholomew's Hospital, London, UK. AD - Institute of Cardiovascular Sciences, University College London, London, UK. FAU - Manisty, Charlotte AU - Manisty C AD - Barts Heart Centre, St. Bartholomew's Hospital, London, UK. AD - Institute of Cardiovascular Sciences, University College London, London, UK. FAU - Moon, James C AU - Moon JC AD - Barts Heart Centre, St. Bartholomew's Hospital, London, UK. AD - Institute of Cardiovascular Sciences, University College London, London, UK. CN - COVIDsortium Investigators* FAU - Valdes, Ana M AU - Valdes AM AD - NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK. AD - Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK. FAU - Boyton, Rosemary J AU - Boyton RJ AD - Department of Infectious Disease, Imperial College London, London, UK. AD - Lung Division, Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK. FAU - Altmann, Daniel M AU - Altmann DM AD - Department of Immunology and Inflammation, Imperial College London, London, UK. LA - eng SI - ClinicalTrials.gov/NCT04318314 GR - MR/S019553/1/MRC_/Medical Research Council/United Kingdom GR - MR/W020610/1/MRC_/Medical Research Council/United Kingdom GR - FS/19/35/34374/BHF_/British Heart Foundation/United Kingdom GR - MR/V027883/1/MRC_/Medical Research Council/United Kingdom GR - MC_PC_20060/MRC_/Medical Research Council/United Kingdom GR - FS/CRTF/21/24128/BHF_/British Heart Foundation/United Kingdom GR - MR/R02622X/1/MRC_/Medical Research Council/United Kingdom GR - 207511/Z/17/Z/WT_/Wellcome Trust/United Kingdom GR - MR/V036939/1/MRC_/Medical Research Council/United Kingdom GR - FS/18/21/33447/BHF_/British Heart Foundation/United Kingdom PT - Clinical Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220308 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Antibodies, Viral) RN - 0 (COVID-19 Vaccines) RN - 0 (HLA-DRB1 Chains) RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - Antibodies, Viral MH - *COVID-19/genetics MH - COVID-19 Vaccines MH - HLA-DRB1 Chains/genetics MH - Histocompatibility Antigens Class I/genetics MH - Humans MH - SARS-CoV-2 PMC - PMC9111350 OTO - NOTNLM OT - COVID-19 OT - HLA OT - SARS-CoV-2 OT - T-cell immunity OT - immunogenetics OT - vaccine COIS- R.J.B. and D.M.A. are members of the Global T cell Expert Consortium and have consulted for Oxford Immunotec outside the submitted work. FIR - Abbass, Hakam IR - Abbass H FIR - Abiodun, Aderonke IR - Abiodun A FIR - Alfarih, Mashael IR - Alfarih M FIR - Alldis, Zoe IR - Alldis Z FIR - Altmann, Daniel M IR - Altmann DM FIR - Amin, Oliver E IR - Amin OE FIR - Andiapen, Mervyn IR - Andiapen M FIR - Artico, Jessica IR - Artico J FIR - Augusto, Joao B IR - Augusto JB FIR - Baca, Georgiana L IR - Baca GL FIR - Bailey, Sasha N L IR - Bailey SNL FIR - Bhuva, Anish N IR - Bhuva AN FIR - Boulter, Alex IR - Boulter A FIR - Bowles, Ruth IR - Bowles R FIR - Boyton, Rosemary J IR - Boyton RJ FIR - Bracken, Olivia V IR - Bracken OV FIR - O'Brien, Ben IR - O'Brien B FIR - Brooks, Tim IR - Brooks T FIR - Bullock, Natalie IR - Bullock N FIR - Butler, David K IR - Butler DK FIR - Captur, Gabriella IR - Captur G FIR - Champion, Nicola IR - Champion N FIR - Chan, Carmen IR - Chan C FIR - Chandran, Aneesh IR - Chandran A FIR - Collier, David IR - Collier D FIR - de Sousa, Jorge Couto IR - de Sousa JC FIR - Couto-Parada, Xose IR - Couto-Parada X FIR - Cutino-Moguel, Teresa IR - Cutino-Moguel T FIR - Davies, Rhodri H IR - Davies RH FIR - Douglas, Brooke IR - Douglas B FIR - Genova, Cecilia IR - Genova C FIR - Dieobi-Anene, Keenan IR - Dieobi-Anene K FIR - Diniz, Mariana O IR - Diniz MO FIR - Ellis, Anaya IR - Ellis A FIR - Feehan, Karen IR - Feehan K FIR - Finlay, Malcolm IR - Finlay M FIR - Fontana, Marianna IR - Fontana M FIR - Forooghi, Nasim IR - Forooghi N FIR - Gaier, Celia IR - Gaier C FIR - Gibbons, Joseph M IR - Gibbons JM FIR - Gilroy, Derek IR - Gilroy D FIR - Hamblin, Matt IR - Hamblin M FIR - Harker, Gabrielle IR - Harker G FIR - Hewson, Jacqueline IR - Hewson J FIR - Hickling, Lauren M IR - Hickling LM FIR - Hingorani, Aroon D IR - Hingorani AD FIR - Howes, Lee IR - Howes L FIR - Hughes, Alun IR - Hughes A FIR - Hughes, Gemma IR - Hughes G FIR - Hughes, Rebecca IR - Hughes R FIR - Itua, Ivie IR - Itua I FIR - Jardim, Victor IR - Jardim V FIR - Lee, Wing-Yiu Jason IR - Lee WJ FIR - Jensen, Melaniepetra IR - Jensen M FIR - Jones, Jessica IR - Jones J FIR - Jones, Meleri IR - Jones M FIR - Joy, George IR - Joy G FIR - Kapil, Vikas IR - Kapil V FIR - Kurdi, Hibba IR - Kurdi H FIR - Lambourne, Jonathan IR - Lambourne J FIR - Lin, Kai-Min IR - Lin KM FIR - Louth, Sarah IR - Louth S FIR - Maini, Mala K IR - Maini MK FIR - Mandadapu, Vineela IR - Mandadapu V FIR - Manisty, Charlotte IR - Manisty C FIR - McKnight, Aine IR - McKnight A FIR - Menacho, Katia IR - Menacho K FIR - Mfuko, Celina IR - Mfuko C FIR - Mitchelmore, Oliver IR - Mitchelmore O FIR - Moon, Christopher IR - Moon C FIR - Moon, James C IR - Moon JC FIR - Munoz-Sandoval, Diana C IR - Munoz-Sandoval DC FIR - Murray, Sam M IR - Murray SM FIR - Noursadeghi, Mahdad IR - Noursadeghi M FIR - Otter, Ashley IR - Otter A FIR - Pade, Corinna IR - Pade C FIR - Palma, Susana IR - Palma S FIR - Parker, Ruth IR - Parker R FIR - Patel, Kush IR - Patel K FIR - Pawarova, Babita IR - Pawarova B FIR - Petersen, Steffen E IR - Petersen SE FIR - Piniera, Brian IR - Piniera B FIR - Pieper, Franziska P IR - Pieper FP FIR - Pope, Daniel IR - Pope D FIR - Prossora, Mary IR - Prossora M FIR - Rannigan, Lisa IR - Rannigan L FIR - Rapala, Alicja IR - Rapala A FIR - Reynolds, Catherine J IR - Reynolds CJ FIR - Richards, Amy IR - Richards A FIR - Robathan, Matthew IR - Robathan M FIR - Rosenheim, Joshua IR - Rosenheim J FIR - Sambile, Genine IR - Sambile G FIR - Schmidt, Nathalie M IR - Schmidt NM FIR - Semper, Amanda IR - Semper A FIR - Seraphim, Andreas IR - Seraphim A FIR - Simion, Mihaela IR - Simion M FIR - Smit, Angelique IR - Smit A FIR - Sugimoto, Michelle IR - Sugimoto M FIR - Swadling, Leo IR - Swadling L FIR - Taylor, Stephen IR - Taylor S FIR - Temperton, Nigel IR - Temperton N FIR - Thomas, Stephen IR - Thomas S FIR - Thornton, George D IR - Thornton GD FIR - Treibel, Thomas A IR - Treibel TA FIR - Tucker, Art IR - Tucker A FIR - Veerapen, Jessry IR - Veerapen J FIR - Vijayakumar, Mohit IR - Vijayakumar M FIR - Welch, Sophie IR - Welch S FIR - Wodehouse, Theresa IR - Wodehouse T FIR - Wynne, Lucinda IR - Wynne L FIR - Zahedi, Dan IR - Zahedi D FIR - Altmann, Daniel M IR - Altmann DM FIR - Boyton, Rosemary J IR - Boyton RJ FIR - Brooks, Tim IR - Brooks T FIR - Chain, Benjamin IR - Chain B FIR - Maini, Mala K IR - Maini MK FIR - Manisty, Charlotte IR - Manisty C FIR - McKnight, Aine IR - McKnight A FIR - Moon, James C IR - Moon JC FIR - Noursadeghi, Mahdad IR - Noursadeghi M FIR - Treibel, Thomas A IR - Treibel TA FIR - Aithal, Guruprasad P IR - Aithal GP FIR - Ashraf, Waheed IR - Ashraf W FIR - Astbury, Stuart IR - Astbury S FIR - Ball, Jonathan K IR - Ball JK FIR - Chappell, Joseph G IR - Chappell JG FIR - Craxford, Simon IR - Craxford S FIR - Cusin, Lola M L IR - Cusin LML FIR - Duncan, Joshua D IR - Duncan JD FIR - Ikram, Adeel IR - Ikram A FIR - Irving, William L IR - Irving WL FIR - Jackson, Hannah J IR - Jackson HJ FIR - Kelly, Anthony IR - Kelly A FIR - Lingaya, Melanie IR - Lingaya M FIR - Marson, Ben A IR - Marson BA FIR - Newham, Jayne IR - Newham J FIR - Nightingale, Jessica IR - Nightingale J FIR - Norrish, Alan IR - Norrish A FIR - Nowicka, Barbara IR - Nowicka B FIR - Ollivere, Benjamin J IR - Ollivere BJ FIR - Tarr, Alexander W IR - Tarr AW FIR - Tighe, Patrick J IR - Tighe PJ FIR - Tsoleridis, Theocharis IR - Tsoleridis T FIR - Urbanowicz, Richard A IR - Urbanowicz RA FIR - Valdes, Ana M IR - Valdes AM FIR - Vijay, Amrita IR - Vijay A EDAT- 2022/02/15 06:00 MHDA- 2022/04/20 06:00 PMCR- 2022/03/08 CRDT- 2022/02/14 09:17 PHST- 2022/01/26 00:00 [revised] PHST- 2021/11/11 00:00 [received] PHST- 2022/01/28 00:00 [accepted] PHST- 2022/02/15 06:00 [pubmed] PHST- 2022/04/20 06:00 [medline] PHST- 2022/02/14 09:17 [entrez] PHST- 2022/03/08 00:00 [pmc-release] AID - IMM13450 [pii] AID - 10.1111/imm.13450 [doi] PST - ppublish SO - Immunology. 2022 May;166(1):68-77. doi: 10.1111/imm.13450. Epub 2022 Mar 8.