Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Abstract

The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified. Science , this issue p. eabd4570 , p. eabd4585 ; see also p. 404

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Affiliated Institutions

• Université Paris Cité FR
• Necmettin Erbakan University TR
• Assistance Publique – Hôpitaux de Paris FR
• Centre d'Investigation Clinique Bichat
• Sorbonne Université FR
• University of Milano-Bicocca IT
• Aix-Marseille Université FR
• Universidad Fernando Pessoa Canarias ES
• Vall d'Hebron Hospital Universitari ES
• Amsterdam University Medical Centers NL
• Sina Hospital IR
• Icahn School of Medicine at Mount Sinai US
• Institut d'Investigació Biomédica de Bellvitge ES
• Université Sorbonne Paris Nord FR
• Bilkent University TR
• Centre National de la Recherche Scientifique FR
• Dasman Diabetes Institute KW
• University of Rome Tor Vergata IT
• Centre d'Immunologie et des Maladies Infectieuses FR
• King Abdulaziz Medical City SA
• Sağlık Bilimleri Üniversitesi TR
• Columbia University US
• Imperial College London GB
• Hôpital Bichat-Claude-Bernard FR
• Amsterdam Neuroscience NL
• University of Brescia IT
• King Abdullah International Medical Research Center SA
• Erasmus Hospital BE
• Centre for Biomedical Network Research on Rare Diseases ES
• Institut de recherche Saint-Louis
• Fund for Scientific Research BE
• KU Leuven BE
• Shahid Beheshti University of Medical Sciences IR
• King Abdulaziz City for Science and Technology SA
• SIB Swiss Institute of Bioinformatics CH
• Université Libre de Bruxelles BE
• Assistance Publique Hôpitaux de Marseille FR
• Universidad de Antioquia CO
• Hôpital Saint-Louis FR
• Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement FR
• Rockefeller University US
• McGill University Health Centre CA
• Office of Extramural Research US
• Institut des Maladies Génétiques Imagine FR
• École Polytechnique Fédérale de Lausanne CH
• Ghent University Hospital BE
• National Guard Health Affairs SA
• Helix (United States) US
• National Institute of Allergy and Infectious Diseases US
• Inserm FR
• Vall d'Hebron Institut de Recerca ES
• Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi TR
• Institució Catalana de Recerca i Estudis Avançats ES
• Universitat Autònoma de Barcelona ES
• Hospital Universitario de Gran Canaria Doctor Negrín ES
• King Saud University SA
• Institut Pasteur FR
• Naval Research Laboratory Information Technology Division
• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia IT
• Masih Daneshvari Hospital IR
• University of Lausanne CH
• Uniformed Services University of the Health Sciences US

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