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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; 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.
  • Astbury S; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
  • Reynolds CJ; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.
  • Butler DK; Department of Infectious Disease, Imperial College London, London, UK.
  • Muñoz-Sandoval DC; Department of Infectious Disease, Imperial College London, London, UK.
  • Lin KM; Department of Infectious Disease, Imperial College London, London, UK.
  • Pieper FP; Department of Infectious Disease, Imperial College London, London, UK.
  • Otter A; Department of Infectious Disease, Imperial College London, London, UK.
  • Kouraki A; National Infection Service, Public Health England, Porton Down, UK.
  • Cusin L; Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.
  • Nightingale J; School of Life Sciences, University of Nottingham, Nottingham, UK.
  • Vijay A; Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.
  • Craxford S; Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.
  • Aithal GP; Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.
  • Tighe PJ; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
  • Gibbons JM; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, UK.
  • Pade C; School of Life Sciences, University of Nottingham, Nottingham, UK.
  • Joy G; Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.
  • Maini M; Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.
  • Chain B; Barts Heart Centre, St. Bartholomew's Hospital, London, UK.
  • Semper A; Division of Infection and Immunity, University College London, London, UK.
  • Brooks T; Division of Infection and Immunity, University College London, London, UK.
  • Ollivere BJ; National Infection Service, Public Health England, Porton Down, UK.
  • McKnight Á; National Infection Service, Public Health England, Porton Down, UK.
  • Noursadeghi M; Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.
  • Treibel TA; Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.
  • Manisty C; Division of Infection and Immunity, University College London, London, UK.
  • Moon JC; Barts Heart Centre, St. Bartholomew's Hospital, London, UK.
  • Valdes AM; Barts Heart Centre, St. Bartholomew's Hospital, London, UK.
  • Boyton RJ; Institute of Cardiovascular Sciences, University College London, London, UK.
  • Altmann DM; Barts Heart Centre, St. Bartholomew's Hospital, London, UK.
Immunology ; 166(1): 68-77, 2022 05.
Article in English | MEDLINE | ID: covidwho-1685320
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*1302 was associated with a 6·7-fold increased risk of case definition symptomatic COVID-19. In terms of immune responsiveness, HLA-DRB1*1502 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*1501 was associated with increased spike T-cell responses following both first and second dose vaccination. Trial registration NCT04318314 and ISRCTN15677965.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Diagnostic study / Randomized controlled trials Topics: Vaccines Limits: Humans Language: English Journal: Immunology Year: 2022 Document Type: Article Affiliation country: Imm.13450

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Diagnostic study / Randomized controlled trials Topics: Vaccines Limits: Humans Language: English Journal: Immunology Year: 2022 Document Type: Article Affiliation country: Imm.13450