Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

Astrid Marchal; Elizabeth T Cirulli; Iva Neveux; Evangelos Bellos; Ryan S Thwaites; Kelly M Schiabor Barrett; Yu Zhang; Ivana Nemes-Bokun; Mariya Kalinova; Andrew Catchpole; Stuart G Tangye; András N Spaan; Justin B Lack; Jade Ghosn; Charles Burdet; Guy Gorochov; Florence Tubach; Pierre Hausfater; COVID Human Genetic Effort; COVIDeF Study Group; French COVID Cohort Study Group; CoV-Contact Cohort; COVID-STORM Clinicians; COVID Clinicians; Orchestra Working Group; Amsterdam UMC Covid-19 Biobank; NIAID-USUHS COVID Study Group; Clifton L Dalgard; Shen-Ying Zhang; Qian Zhang; Christopher Chiu; Jacques Fellay; Joseph J Grzymski; Vanessa Sancho-Shimizu; Laurent Abel; Jean-Laurent Casanova; Aurélie Cobat; Alexandre Bolze

doi:10.1016/j.xhgg.2024.100300

Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection

HGG Adv. 2024 Apr 26:100300. doi: 10.1016/j.xhgg.2024.100300. Online ahead of print.

Authors

Astrid Marchal¹, Elizabeth T Cirulli², Iva Neveux³, Evangelos Bellos⁴, Ryan S Thwaites⁵, Kelly M Schiabor Barrett², Yu Zhang⁶, Ivana Nemes-Bokun⁴, Mariya Kalinova⁷, Andrew Catchpole⁷, Stuart G Tangye⁸, András N Spaan⁹, Justin B Lack¹⁰, Jade Ghosn¹¹, Charles Burdet¹², Guy Gorochov¹³, Florence Tubach¹⁴, Pierre Hausfater¹⁵; COVID Human Genetic Effort; COVIDeF Study Group; French COVID Cohort Study Group; CoV-Contact Cohort; COVID-STORM Clinicians; COVID Clinicians; Orchestra Working Group; Amsterdam UMC Covid-19 Biobank; NIAID-USUHS COVID Study Group; Clifton L Dalgard¹⁶, Shen-Ying Zhang¹⁷, Qian Zhang¹⁷, Christopher Chiu⁴, Jacques Fellay¹⁸, Joseph J Grzymski¹⁹, Vanessa Sancho-Shimizu²⁰, Laurent Abel¹⁷, Jean-Laurent Casanova²¹, Aurélie Cobat²², Alexandre Bolze²³

Affiliations

¹ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France, EU; University Paris Cité, Imagine Institute, Paris, France, EU.
² Helix, San Mateo, CA, USA.
³ Department of Internal Medicine, University of Nevada School of Medicine, Reno, NV, USA.
⁴ Department of Infectious Diseases, Imperial College London, London, United Kingdom.
⁵ National Heart and Lung Institute, Imperial College London, London, United Kingdom.
⁶ Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, Bethesda, MD, USA.
⁷ hVIVO Services Ltd., London, UK.
⁸ Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia.
⁹ St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands, EU.
¹⁰ NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.
¹¹ Infection, Antimicrobials, Modelling, Evolution (IAME), INSERM, UMR1137, University of Paris, Paris, France, EU; AP-HP, Bichat Claude Bernard Hospital, Infectious and Tropical Diseases Department, Paris, France, EU.
¹² Infection, Antimicrobials, Modelling, Evolution (IAME), INSERM, UMR1137, University of Paris, Paris, France, EU; Epidémiologie clinique du Centre d'Investigation Clinique (CIC-EP), INSERM CIC 1425, Hôpital Bichat, 75018 Paris, France, EU; Département Epidémiologie, Biostatistiques et Recherche Clinique, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, 75018 Paris, France, EU.
¹³ Sorbonne Université, INSERM Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Département d'immunologie Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France, EU.
¹⁴ Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Département de Santé Publique, Unité de Recherche Clinique PSL-CFX, CIC-1901, Paris, France, EU.
¹⁵ Emergency Department, Hôpital Pitié-Salpêtrière, APHP-Sorbonne Université, Paris, France, EU; GRC-14 BIOFAST Sorbonne Université, UMR INSERM 1135, CIMI, Sorbonne Université, Paris, France, EU.
¹⁶ Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹⁷ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France, EU; University Paris Cité, Imagine Institute, Paris, France, EU; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
¹⁸ School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland; Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
¹⁹ Department of Internal Medicine, University of Nevada School of Medicine, Reno, NV, USA; Renown Health, Reno, NV, USA.
²⁰ Department of Infectious Diseases, Imperial College London, London, United Kingdom; Centre for Paediatrics and Child Health, Faculty of Medicine, Imperial College London, London, UK.
²¹ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France, EU; University Paris Cité, Imagine Institute, Paris, France, EU; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Department of Pediatrics, Necker Hospital for Sick Children, Paris, France, EU; Howard Hughes Medical Institute, New York, NY, USA.
²² Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France, EU; University Paris Cité, Imagine Institute, Paris, France, EU; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Electronic address: aurelie.cobat@inserm.fr.
²³ Helix, San Mateo, CA, USA. Electronic address: alexandre.bolze@gmail.com.

PMID: 38678364
DOI: 10.1016/j.xhgg.2024.100300

Abstract

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B*15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B*15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the US (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B*15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.