Autoantibodies against type I IFNs 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

Keywords

Affiliated Institutions

• Science for Life Laboratory SE
• Université Paris Cité FR
• Assistance Publique – Hôpitaux de Paris FR
• Centre d'Investigation Clinique Bichat
• Sorbonne Université FR
• University of Milano-Bicocca IT
• Yale University US
• Mútua Terrassa ES
• Universidad Fernando Pessoa Canarias ES
• Haukeland University Hospital
• Amsterdam University Medical Centers NL
• Istituti di Ricovero e Cura a Carattere Scientifico IT
• Garvan Institute of Medical Research AU
• IrsiCaixa ES
• National Institute of Dental and Craniofacial Research US
• Howard Hughes Medical Institute US
• Policlinico San Matteo Fondazione IT
• Université Claude Bernard Lyon 1 FR
• University of Amsterdam NL
• UNSW Sydney AU
• Karolinska Institutet SE
• Centre National de la Recherche Scientifique FR
• Centre d'Immunologie et des Maladies Infectieuses FR
• Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol ES
• Universitat de Vic - Universitat Central de Catalunya ES
• French Clinical Research Infrastructure Network FR
• Hôpital Bichat-Claude-Bernard FR
• Amsterdam Neuroscience NL
• University Medical Center Utrecht NL
• University of Brescia IT
• Universitat de Barcelona ES
• University of Pavia IT
• Hôpital Foch FR
• Aarhus University DK
• Aarhus University Hospital DK
• Rockefeller University US
• McGill University Health Centre CA
• Office of Extramural Research US
• Centre International de Recherche en Infectiologie FR
• Institut des Maladies Génétiques Imagine FR
• Hospices Civils de Lyon FR
• Tartu University Hospital EE
• Ghent University Hospital BE
• Collège de France FR
• National Institutes of Health US
• National Institute of Allergy and Infectious Diseases US
• Helix (United States) US
• Université de Lorraine FR
• Inserm FR
• Karolinska University Hospital SE
• Vita-Salute San Raffaele University IT
• Institució Catalana de Recerca i Estudis Avançats ES
• Hospital Universitario de Gran Canaria Doctor Negrín ES
• Institute of Genetics and Biophysics IT
• Pitié-Salpêtrière Hospital FR
• Institut Pasteur FR
• Naval Research Laboratory Information Technology Division
• University of Tartu EE
• St Vincent's Clinic AU
• University of Bergen
• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia IT

Related Publications