Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.

ADMA Biologics Inc Ramsey NJ 07446

Aix Marseille University School of Medicine EA 3279 Centre d'Études et de Recherche sur les Services de Santé et la Qualité de vie Health Service Research and Quality of Life Center 13385 Marseille France

Allergy and Clinical Immunology Unit Department of Medicine Tel Aviv Sourasky Medical Center 6423906 Tel Aviv Israel

Catalan Institution of Research and Advanced Studies 08010 Barcelona Spain

Center for Autoimmune Disease Research School of Medicine and Health Sciences Universidad del Rosario 110111 Bogotá Colombia

Center for Autoimmune Disease Research School of Medicine and Health Sciences Universidad del Rosario 111211 Bogotá Colombia

Centre for Biomedical Research on Rare Diseases U759 Instituto de Salud Carlos 3 28029 Madrid Spain

Centre Hospitalier Universitaire de Lille Pôle de Réanimation Hôpital Roger Salengro Lille 59000 Lille France

Centre International de Recherche en Infectiologie INSERM U1111 CNRS UMR5308 Ecole Normale Supérieure de Lyon Université Claude Bernard Lyon 1 69007 Lyon France

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias Instituto de Salud Carlos 3 28029 Madrid Spain

Cerba HealthCare 92130 Issy les Moulineaux France

CHemato oncology Research Laboratory of Associazione italiana contro le leucemie linfomi e mieloma Diagnostic Departement Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia 25123 Brescia Italy

Clinical Immunology Unit Department of Pediatric Infectious Disease Centre Hospitalier Universitaire Ibn Roucshd 20360 Casablanca Morocco

Cohorte Constances Groupe Hospitalier Universitaire centre Assistance Publique Hôpitaux de Paris Université de Paris 94800 Villejuif France

College of Medicine Imam Abdulrahman Bin Faisal University Dammam 34212 Saudi Arabia

Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas Instituto de Salud Carlos 3 28029 Madrid Spain

Département d'Immunologie Assistance Publique Hôpitaux de Paris Hôpital Pitié Salpétrière 75015 Paris France

Département Epidémiologie Biostatistiques et Recherche Clinique Hôpital Bichat Assistance Publique Hôpitaux de Paris 75018 Paris France

Department of Age Related Healthcare Tallaght University Hospital Dublin D24 NR0A Ireland

Department of Biomedicine Aarhus University 8000 Aarhus Denmark

Department of Biosciences and Nutrition Karolinska Institutet 171 77 Stockholm Sweden

Department of Children's Diseases and Pediatric Surgery 1 Horbachevsky Ternopil National Medical University 46022 Ternopil Ukraine

Department of Clinical Immunology Aarhus University Hospital 8000 Aarhus Denmark

Department of Clinical Laboratory Hospital Universitari de Bellvitge The Bellvitge Biomedical Research Institute 08908 Barcelona Spain

Department of Clinical Sciences Universidad Fernando Pessoa Canarias 35450 Las Palmas de Gran Canaria Spain

Department of Critical Care Medicine Clínica Universidad de La Sabana 250001 Chía Colombia

Department of Epidemiology Infectious Disease Control and Prevention Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima 734 8553 Japan

Department of Genetics Yale University School of Medicine New Haven CT 06520

Department of Human Genomics and Evolution Collège de France 75231 Paris France

Department of Immunology 2nd Faculty of Medicine Charles University and University Hospital in Motol 150 06 Prague Czech Republic

Department of Immunology CIC1408 Groupe sur l'Immunité des Muqueuses et des Agents Pathogènes Centre International de Recherche en Infectiologie INSERM U1111 University Hospital of Saint Étienne 42000 Saint Étienne France

Department of Immunology Dmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology Moscow Russia 117997

Department of Immunology Hospital Universitari de Bellvitge The Bellvitge Biomedical Research Institute 08908 Barcelona Spain

Department of Immunology Institute of Biomedical Sciences University of São Paulo 05508 060 São Paulo Brazil

Department of Immunology University Hospital of Gran Canaria Dr Negrin Canarian Health System 35010 Las Palmas de Gran Canaria Spain

Department of Infection Control and Prevention Medical Hospital Tokyo Medical and Dental University Tokyo 113 8655 Japan

Department of Infectious Diseases Aarhus University Hospital 8000 Aarhus Denmark

Department of Infectious Diseases and Immunity University of Vic Central University of Catalonia 08500 Vic Spain

Department of Infectious Diseases San Gerardo Hospital University of Milano Bicocca 20900 Monza Italy

Department of Internal Medicine 2 Medical University of Innsbruck 6020 Innsbruck Austria

Department of Internal Medicine Hospital Universitari de Bellvitge The Bellvitge Biomedical Research Institute 08908 Barcelona Spain

Department of Internal Medicine Infanta Leonor University Hospital 28031 Madrid Spain

Department of Medical Genetics Acibadem University School of Medicine 34750 Istanbul Turkey

Department of Medical Gerontology School of Medicine Trinity College Dublin Dublin D08 W9RT Ireland

Department of Medical Microbiology University Medical Center Utrecht 3584 CX Utrecht The Netherlands

Department of Medicine Division of Infectious Diseases McGill University Health Centre Montréal QC H4A 3J1 Canada

Department of Microbiology Universidad de La Sabana 250001 Chía Colombia

Department of Molecular Biology and Genetics Bilkent University 06800 Ankara Turkey

Department of Nephrology and Transplantation Necker University Hospital Assistance Publique Hôpitaux de Paris 75743 Paris France

Department of Neurology Amsterdam UMC Amsterdam Neuroscience University of Amsterdam Amsterdam 1105 AZ The Netherlands

Department of Neurology Institute of Neurodegenerative Diseases Bordeaux University Hospital F 33000 Bordeaux France

Department of Neurosurgery Yale University School of Medicine New Haven CT 06510

Department of Paediatric Immunology and Pulmonology Center for Primary Immunodeficiency Ghent Jeffrey Modell Diagnosis and Research Center Ghent University Hospital 9000 Ghent Belgium

Department of Paediatrics and Adolescent Medicine University of Hong Kong Hong Kong 999077 China

Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104

Department of Pediatrics and Developmental Biology Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University Tokyo 113 8510 Japan

Department of Pediatrics British Columbia Children's Hospital University of British Columbia Vancouver BC V6H 0B3 Canada

Department of Pediatrics Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima 734 8553 Japan

Department of Pediatrics Jeffrey Modell Diagnostic and Research Network Center University Hospitals Leuven 3000 Leuven Belgium

Department of Pediatrics King Fahad Hospital of the University Al Khobar 34445 Saudi Arabia

Department of Pharmacology and Molecular Therapeutics Uniformed Services University of the Health Sciences Bethesda MD 20814

Diabetes Research Institute Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute 20132 Milan Italy

Division of Geriatric Medicine Tours University Medical Center 37044 Tours France

EA 7426 Pathophysiology of Injury Induced Immunosuppression Université Claude Bernard Lyon 1 Hospices Civils de Lyon BioMérieux Hôpital Edouard Herriot 69437 Lyon France

EA3518 Institut Universitaire d'Hématologie Hôpital Saint Louis Université de Paris 75010 Paris France

Epidémiologie clinique du Centre d'Investigation Clinique INSERM CIC 1425 Hôpital Bichat 75018 Paris France

Etablissement Français du Sang 93218 La Plaine Saint Denis France

Etablissement Français du Sang Auvergne Rhône Alpes 42000 Saint Étienne France

Faculdades Pequeno Príncipe Instituto de Pesquisa Pelé Pequeno Príncipe 80250 200 Curitiba Brazil

Faculty of Medical Sciences University Goce Delchev Štip 2000 Republic of North Macedonia

Feinstein Institutes for Medical Research Northwell Health Manhasset NY 11030

Fundació Docència i Recerca Mutua Terrassa 08221 Terrassa Spain

Fundación Rioja Salud Centro de Investigación Biomédica de La Rioja 26006 Logroño Spain

Garvan Institute of Medical Research Sydney NWS 2010 Australia

Groupe de Recherche Clinique Cardiovascular and Respiratory Manifestations of Acute Lung Injury and Sepsis Faculté de santé de Créteil Université Paris Est Créteil 94010 Créteil Cedex France

Hematology and Bone Marrow Transplantation Unit Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele University Vita Salute San Raffaele 20132 Milano Italy

HHMI Rockefeller University New York NY 10065

Hospices Civils de Lyon 69002 Lyon France

Hospital Universitari MútuaTerrassa Universitat de Barcelona 08193 Barcelona Spain

Human Evolutionary Genetics Unit Institut Pasteur CNRS UMR 2000 75015 Paris France

Hypoxia and Lung INSERM U1272 Avicenne Hospital Assistance Publique Hôpitaux de Paris 93022 Bobigny France

Imagine Institute Université de Paris INSERM UMR 1163 75015 Paris France

Imagine Institute University of Paris 75015 Paris France

Immunology Division Genetics Department Hospital Universitari Vall d'Hebron Vall d'Hebron Research Institute Universitat Autònoma de Barcelona 08035 Barcelona Spain

Immunology Research Lab College of Medicine King Saud University 11362 Riyadh Saudi Arabia

Immunopathology Federation Lyon Immunopathology Federation Hospices Civils de Lyon 69002 Lyon France

Infectious Disease Susceptibility Program Research Institute of the McGill University Health Centre Montréal QC H4A 3J1 Canada

INSERM U1019 CNRS UMR9017 Center for Infection and Immunity of Lille Institut Pasteur de Lille University of Lille 59000 Lille France

INSERM U1138 Centre de Recherche des Cordeliers 75006 Paris France

INSERM U1259 Morphogenèse et Antigénicité du VIH et des Virus des Hépatites Université de Tours 37044 Tours France

INSERM UMRS 1166 iCAN Institute of Cardiometabolism and Nutrition 75013 Paris France

Institut d'Investigacions Biomèdiques August Pi i Sunyer 08036 Barcelona Spain

Institut Hospitalo Universitaire Méditerranée Infection Unité des Virus Émergents Aix Marseille University Institut pour la Recherche et le Développment 190 INSERM 1207 13005 Marseille France

Institut Necker Enfants Malades INSERM U1151 CNRS UMR 8253 Université de Paris 75015 Paris France

Institute for Biomedical Research Spanish National Research Council 08036 Barcelona Spain

Institute for Health Science Research Germans Trias i Pujol 08916 Badalona Spain

Institute for Systems Biology Seattle WA 98109

Institute of Biomedicine and Translational Medicine University of Tartu 50090 Tartu Estonia

Institute of Public Health of the Republic of North Macedonia Skopje 1000 Republic of North Macedonia

Intensive Care Medicine Donostia University Hospital Biodonostia Institute of Donostia 20014 San Sebastián Spain

Intensive Care Medicine University Hospital of Gran Canaria Dr Negrín Canarian Health System 35010 Las Palmas de Gran Canaria Spain

Intensive Care Unit Grand Hôpital de l'Est Francilien Site de Marne La Vallée 77600 Jossigny France

Interactions Hôte Greffon Tumeur et Ingénierie Cellulaire et Génique INSERM Etablissement Français du Sang Université de Franche Comté 25000 Besançon France

Internal Medicine Department Lariboisière Hospital Assistance Publique Hôpitaux de Paris University of Paris 75010 Paris France

International Center of Research in Infectiology Lyon University INSERM U1111 CNRS UMR 5308 ENS Ecole Nationale Supérieure Université Claude Bernard Lyon 1 69365 Lyon France

IrsiCaixa AIDS Research Institute 08916 Badalona Spain

Joint Research Unit Hospices Civils de Lyon BioMérieux Hospices Civils de Lyon Lyon Sud Hospital 69495 Pierre Bénite France

Laboratoire d'Immunologie Clinique Inflammation et Allergie Faculty of Medicine and Pharmacy Hassan 2 University 20250 Casablanca Morocco

Laboratoire d'Immunologie Hospices Civils de Lyon Hôpital Edouard Herriot 69437 Lyon France

Laboratory of Clinical Immunology and Microbiology Division of Intramural Research National Institute of Allergy and Infectious Diseases NIH Bethesda MD 20892

Laboratory of Human Genetics of Infectious Diseases Necker Branch INSERM U1163 Necker Hospital for Sick Children 75015 Paris France

Laboratory of Immunobiology Center for Clinical Experimental Surgery and Translational Research Biomedical Research Foundation of the Academy of Athens 11527 Athens Greece

Laboratory of Inborn Errors of Immunity Department of Microbiology Immunology and Transplantation Katholieke Universiteit Leuven 3000 Leuven Belgium

Laboratory of Molecular Immunology Rockefeller University New York NY 10065

Laboratory of Virology and Infectious Disease Rockefeller University New York NY 10065

Medical Intensive Care Unit University Hospitals Leuven 3000 Leuven Belgium

Meram Faculty of Medicine Necmettin Erbakan University 42080 Konya Turkey

Microbes Evolution Phylogénie et Infection Institut Hospitalo Universitaire Méditerranée Infection Institut de Recherche pour le Développement Assistance Publique Hôpitaux de Marseille Aix Marseille Université 13005 Marseille France

National Institute of Allergy and Infectious Diseases Clinical Genomics Program NIH Bethesda MD 20892

National Referee Centre for Rheumatic and Autoimmune and Systemic Diseases in Children 69000 Lyon France

Neurometabolic Diseases Laboratory The Bellvitge Biomedical Research Institute 08908 Barcelona Spain

Paris Cardiovascular Research Center INSERM Université de Paris 75015 Paris France

Pediatric Clinic Fondazione Istituto di Ricovero e Cura a carattere scientifico Policlinico San Matteo Department of Clinical Surgical Diagnostic and Pediatric Sciences University of Pavia 27100 Pavia Italy

Pediatric Department and Centro Tettamanti European Reference Network PaedCan EuroBloodNet European Reference Network for Rare Hereditary Metabolic Disorders Ospedale San Gerardo 20900 Monza Italy

Pediatric Infectious Diseases and Immunodeficiencies Unit Hospital Universitari Vall d'Hebron Vall d'Hebron Research Institute Universitat Autònoma de Barcelona 08035 Barcelona Spain

Precision Medicine Unit Lausanne University Hospital and University of Lausanne 1011 Lausanne Switzerland

Primary Immunodeficiencies Group Department of Microbiology and Parasitology School of Medicine University of Antioquia UdeA 050010 Medellín Colombia

Primary Immunodeficiencies Group University of Antioquia UdeA 050010 Medellin Colombia

Réanimation Médicale et Toxicologique Hôpital Lariboisière Assistance Publique Hôpitaux de Paris Université de Paris INSERM UMRS 1144 75010 Paris France

Sackler Faculty of Medicine Tel Aviv University 6997801 Tel Aviv Israel

Santé Ingéniérie Biologie St Etienne INSERM U1059 University of Lyon Université Jean Monnet Saint Etienne 42000 Saint Étienne France

School of Life Sciences École Polytechnique Fédérale de Lausanne 1015 Lausanne Switzerland

School of Microbiology University of Antioquia UdeA 050010 Medellin Colombia

Service d'Evaluation Médicale Hôpitaux Universitaires de Marseille Assistance Publique Hôpitaux de Marseille 13005 Marseille France

Service d'Hématologie Biologique Hôpital Lariboisière Assistance Publique Hôpitaux de Paris Université de Paris 75010 Paris France

Service de Bactériologie Virologie et Hygiène Hospitalière Centre Hospitalier Universitaire de Tours 37044 Tours France

Service de Biologie Clinique and UMR S 1176 Hôpital Foch 92150 Suresnes France

Service de Biologie Médicale Centre Hospitalier Intercommunal Robert Ballanger 93600 Aulnay sous Bois France

Service de Médecine Intensive Réanimation Hôpitaux Universitaires Henri Mondor Assistance Publique Hôpitaux de Paris 94010 Créteil France

Service de Médecine Interne Hôpital Universitaire Jean Verdier Assistance Publique Hôpitaux de Paris 93140 Bondy France

Service de Parasitologie Mycologie Groupe Hospitalier Pitié Salpêtrière Assistance Publique Hôpitaux de Paris 75013 Paris France

Service de Réanimation Médicale et des Maladies Infectieuses Hôpital Bichat Assistance Publique Hôpitaux de Paris Nord Université de Paris F 75018 Paris France

Sharjah Institute for Medical Research College of Medicine University of Sharjah 27272 Sharjah United Arab Emirates

Shupyk National Healthcare University of Ukraine 04112 Kyiv Ukraine

Sorbonne Université Hôpital Pitié Salpêtrière Médecine Intensive Réanimation Assistance Publique Hôpitaux de Paris 75013 Paris France

Sorbonne Université INSERM Centre d'Immunologie et des Maladies Infectieuses 75013 Paris France

Sorbonne Université INSERM U1136 Institut Pierre Louis d'Epidémiologie et de Santé Publique Assistance Publique Hôpitaux de Paris Hôpital Pitié Salpêtrière Service de Virologie 75013 Paris France

St Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch Rockefeller University New York NY 10065

St Vincent's Clinical School Faculty of Medicine and Health University of New South Wales Sydney NWS 2010 Australia

Swiss Institute of Bioinformatics 1015 Lausanne Switzerland

The Genetics Institute and Genomics Center Tel Aviv Sourasky Medical Center 6423906 Tel Aviv Israel

Translational Immunology Unit Institut Pasteur Université Paris Cité 75015 Paris France

Université de Paris Infection Antimicrobials Modelling Evolution UMR 1137 INSERM 75870 Paris France

University of Bordeaux INSERM Bordeaux Population Health Center UMR1219 F 33000 Bordeaux France

University of Lille INSERM Centre Hospitalier Universitaire de Lille Institut Pasteur de Lille U1011 European Genomic Institute for Diabetes F 59000 Lille France

University of São Paulo 05508 060 São Paulo Brazil

Vita Salute San Raffaele University and Clinical Genomics Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele 20132 Milan Italy

Yale Center for Genome Analysis Yale School of Medicine New Haven CT 06511

Před aktualizací

Res Sq. 2022 Jan 14:rs.3.rs-1225906. doi: 10.21203/rs.3.rs-1225906/v1. PubMed

Komentář v

J Interferon Cytokine Res. 2022 Nov;42(11):590-591. doi: 10.1089/jir.2022.0156. PubMed

Zobrazit více v PubMed

Hu B., Guo H., Zhou P., Shi Z. L., Characteristics of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol. 19, 141–154 (2021). PubMed PMC

Telenti A., et al. , After the pandemic: Perspectives on the future trajectory of COVID-19. Nature 596, 495–504 (2021). PubMed

Zhang Q., Bastard P., Cobat A., Casanova J. L.; COVID Human Genetic Effort, Human genetic and immunological determinants of critical COVID-19 pneumonia. Nature 603, 587–598 (2022). PubMed PMC

Pei S., Yamana T. K., Kandula S., Galanti M., Shaman J., Burden and characteristics of COVID-19 in the United States during 2020. Nature 598, 338–341 (2021). PubMed

Zhang Q., et al. ; COVID Human Genetic Effort, Life-threatening COVID-19: Defective interferons unleash excessive inflammation. Med (N Y) 1, 14–20 (2020). PubMed PMC

O’Driscoll M., et al. , Age-specific mortality and immunity patterns of SARS-CoV-2. Nature 590, 140–145 (2021). PubMed

Levin A. T., et al. , Assessing the age specificity of infection fatality rates for COVID-19: Systematic review, meta-analysis, and public policy implications. Eur. J. Epidemiol. 35, 1123–1138 (2020). PubMed PMC

Brodin P., Immune determinants of COVID-19 disease presentation and severity. Nat. Med. 27, 28–33 (2021). PubMed

Duncan C. J. A., Randall R. E., Hambleton S., Genetic lesions of Type I interferon signalling in human antiviral immunity. Trends Genet. 37, 46–58 (2021). PubMed PMC

Casanova J. L., Su H. C.; COVID Human Genetic Effort, A global effort to define the human genetics of protective immunity to SARS-CoV-2 infection. Cell 181, 1194–1199 (2020). PubMed PMC

Bastard P., et al. ; HGID Lab; COVID Clinicians; COVID-STORM Clinicians; NIAID Immune Response to COVID Group; NH-COVAIR Study Group; Danish CHGE; Danish Blood Donor Study; St. James’s Hospital; SARS CoV2 Interest group; French COVID Cohort Study Group; Imagine COVID-Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19; Biobank Investigators; COVID Human Genetic Effort; CONSTANCES cohort; 3C-Dijon Study; Cerba Health-Care; Etablissement du Sang study group, Autoantibodies neutralizing type I IFNs are present in ∼4% of uninfected individuals over 70 years old and account for ∼20% of COVID-19 deaths. Sci. Immunol. 6, eabl4340 (2021). PubMed PMC

Bastard P., et al. ; HGID Lab; NIAID-USUHS Immune Response to COVID Group; COVID Clinicians; COVID-STORM Clinicians; Imagine COVID Group; French COVID Cohort Study Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort, Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 370, eabd4585 (2020). PubMed PMC

Asano T., et al. ; COVID Human Genetic Effort; COVID-STORM Clinicians; COVID Clinicians; Imagine COVID Group; French COVID Cohort Study Group; CoV-Contact Cohort; Amsterdam UMC Covid-; Biobank; NIAID-USUHS COVID Study Group, X-linked recessive TLR7 deficiency in ∼1% of men under 60 years old with life-threatening COVID-19. Sci. Immunol. 6, eabl4348 (2021). PubMed PMC

Zhang Q., et al. ; COVID-STORM Clinicians; COVID Clinicians; Imagine COVID Group; French COVID Cohort Study Group; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort; NIAID-USUHS/TAGC COVID Immunity Group, Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370, eabd4570 (2020). PubMed PMC

Khanmohammadi S., Rezaei N., Khazaei M., Shirkani A., A case of autosomal recessive interferon alpha/beta receptor alpha chain (IFNAR1) deficiency with severe COVID-19. J. Clin. Immunol. 42, 19–24 (2021). PubMed PMC

Abolhassani H., et al. , Inherited IFNAR1 deficiency in a child with both critical COVID-19 pneumonia and multisystem inflammatory syndrome. J. Clin. Immunol., 10.1007/s10875-022-01215-7 (2022). PubMed DOI PMC

Schmidt A., et al. , TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19. NPJ Genom. Med. 6, 55 (2021). PubMed PMC

Abolhassani H., et al. , X-linked TLR7 deficiency underlies critical COVID-19 pneumonia in a male patient with ataxia-telangiectasia. J. Clin. Immunol. 42, 1–9 (2021). PubMed PMC

Casanova J. L., Abel L., Mechanisms of viral inflammation and disease in humans. Science 374, 1080–1086 (2021). PubMed PMC

Goncalves D., et al. , Antibodies against type I interferon: Detection and association with severe clinical outcome in COVID-19 patients. Clin. Transl. Immunology 10, e1327 (2021). PubMed PMC

Shaw E. R., et al. , Temporal dynamics of anti-type 1 interferon autoantibodies in COVID-19 patients. Clin. Infect. Dis., 10.1093/cid/ciab1002 (2021). PubMed DOI PMC

Savvateeva E., et al. , Microarray-based detection of antibodies against SARS-CoV-2 proteins, common respiratory viruses and Type I interferons. Viruses 13, 2553 (2021). PubMed PMC

Koning R., Bastard P., Casanova J. L., Brouwer M. C., van de Beek D.; with the Amsterdam U.M.C. COVID-19 Biobank Investigators, Autoantibodies against type I interferons are associated with multi-organ failure in COVID-19 patients. Intensive Care Med. 47, 704–706 (2021). PubMed PMC

Troya J., et al. , Neutralizing autoantibodies to Type I IFNs in >10% of patients with severe COVID-19 pneumonia hospitalized in Madrid, Spain. J. Clin. Immunol. 41, 914–922 (2021). PubMed PMC

van der Wijst M. G. P., et al. ; UCSF COMET consortium, Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19. Sci. Transl. Med. 13, eabh2624 (2021). PubMed PMC

Vazquez S. E., et al. , Neutralizing autoantibodies to Type I interferons in COVID-19 convalescent donor plasma. J. Clin. Immunol. 41, 1169–1171 (2021). PubMed PMC

Wang E. Y., et al. ; Yale IMPACT Team, Diverse functional autoantibodies in patients with COVID-19. Nature 595, 283–288 (2021). PubMed

Abers M. S., et al. , Neutralizing type-I interferon autoantibodies are associated with delayed viral clearance and intensive care unit admission in patients with COVID-19. Immunol. Cell Biol. 99, 917–921 (2021). PubMed PMC

Chauvineau-Grenier A., et al. , Autoantibodies neutralizing type I interferons in 20% of COVID-19 deaths in a French hospital. J. Clin. Immunol., https://doi.org/10.1007/s10875-021-01203-3 (2022). PubMed PMC

Solanich X., et al. , Pre-existing autoantibodies neutralizing high concentrations of type I interferons in almost 10% of COVID-19 patients admitted to intensive care in Barcelona. J. Clin. Immunol. 41, 1733–1744 (2021). PubMed PMC

Raadsen M. P., et al. , Interferon-α2 auto-antibodies in convalescent plasma therapy for COVID-19. J. Clin. Immunol. 42, 232–239 (2021). PubMed PMC

Chang S. E., et al. , New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nat. Commun. 12, 5417 (2021). PubMed PMC

Ziegler C. G. K., et al. , Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. Cell 184, 4713–4733.e22 (2021). PubMed PMC

Acosta-Ampudia Y., et al. ; CP-COVID-19 group, COVID-19 convalescent plasma composition and immunological effects in severe patients. J. Autoimmun. 118, 102598 (2021). PubMed PMC

Carapito R., et al. , Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort. Sci. Transl. Med. 14, eabj7521 (2022). PubMed

Bastard P., et al. , Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1. J. Exp. Med. 218, e20210554 (2021). PubMed PMC

van der Wijst M. G. P., et al. , Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19. Sci. Transl. Med. 13, eabh2624 (2021). PubMed PMC

Galani I. E., et al. , Untuned antiviral immunity in COVID-19 revealed by temporal type I/III interferon patterns and flu comparison. Nat. Immunol. 22, 32–40 (2021). PubMed

Sposito B., et al. , The interferon landscape along the respiratory tract impacts the severity of COVID-19. Cell 184, 4953–4968.e16 (2021). PubMed PMC

Lopez J., et al. , Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs. J. Exp. Med. 218, e20211211 (2021). PubMed PMC

Blanco-Melo D., et al. , Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181, 1036–1045.e9 (2020). PubMed PMC

Israelow B., et al. , Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. J. Exp. Med. 217, e20201241 (2020). PubMed PMC

Döffinger R., et al. , Autoantibodies to interferon-gamma in a patient with selective susceptibility to mycobacterial infection and organ-specific autoimmunity. Clin. Infect. Dis. 38, e10–e14 (2004). PubMed

Höflich C., et al. , Naturally occurring anti-IFN-gamma autoantibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovenenans. Blood 103, 673–675 (2004). PubMed

Kampmann B., et al. , Acquired predisposition to mycobacterial disease due to autoantibodies to IFN-gamma. J. Clin. Invest. 115, 2480–2488 (2005). PubMed PMC

Puel A., et al. , Recurrent staphylococcal cellulitis and subcutaneous abscesses in a child with autoantibodies against IL-6. J. Immunol. 180, 647–654 (2008). PubMed

Puel A., et al. , Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J. Exp. Med. 207, 291–297 (2010). PubMed PMC

Ku C. L., Chi C. Y., von Bernuth H., Doffinger R., Autoantibodies against cytokines: Phenocopies of primary immunodeficiencies? Hum. Genet. 139, 783–794 (2020). PubMed PMC

Kisand K., et al. , Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J. Exp. Med. 207, 299–308 (2010). PubMed PMC

Rosen L. B., et al. , Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis. Clin. Infect. Dis. 60, 1017–1025 (2015). PubMed PMC

Casanova J. L., Abel L., Lethal infectious diseases as inborn errors of immunity: Toward a synthesis of the germ and genetic theories. Annu. Rev. Pathol. 16, 23–50 (2021). PubMed PMC

Bastard P., Why do people die from COVID-19? Science 375, 829–830 (2022). PubMed

Bastard P., Zhang Q., Zhang S. Y., Jouanguy E., Casanova J. L., Type I interferons and SARS-CoV-2: From cells to organisms. Curr. Opin. Immunol. 74, 172–182 (2022). PubMed PMC

Morabia A., Ten Have T., Landis J. R., Empirical evaluation of the influence of control selection schemes on relative risk estimation: The Welsh nickel workers study. Occup. Environ. Med. 52, 489–493 (1995). PubMed PMC

Bartleson J. M., et al. , SARS-CoV-2, COVID-19 and the ageing immune system. Nat Aging 1, 769–782 (2021). PubMed PMC

Splunter M. V., et al. , Plasmacytoid dendritic cell and myeloid dendritic cell function in ageing: A comparison between elderly and young adult women. PLoS One 14, e0225825 (2019). PubMed PMC

Schultze J. L., Aschenbrenner A. C., COVID-19 and the human innate immune system. Cell 184, 1671–1692 (2021). PubMed PMC

Stark G. R., Darnell J. E. Jr., The JAK-STAT pathway at twenty. Immunity 36, 503–514 (2012). PubMed PMC

Pierce C. A., et al. , Natural mucosal barriers and COVID-19 in children. JCI Insight 6, 148694 (2021). PubMed PMC

Manry J., et al. , Evolutionary genetic dissection of human interferons. J. Exp. Med. 208, 2747–2759 (2011). PubMed PMC

Ng C. T., et al. , Blockade of interferon Beta, but not interferon alpha, signaling controls persistent viral infection. Cell Host Microbe 17, 653–661 (2015). PubMed PMC

Vinh D. C., et al. ; COVID Human Genetic Effort, Harnessing Type I IFN immunity against SARS-CoV-2 with early administration of IFN-β. J. Clin. Immunol. 41, 1425–1442 (2021). PubMed PMC

Weinreich D. M., et al. ; Trial Investigators, REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N. Engl. J. Med. 384, 238–251 (2021). PubMed PMC

Bastard P., et al. , Interferon-β therapy in a patient with incontinentia pigmenti and autoantibodies against Type I IFNs infected with SARS-CoV-2. J. Clin. Immunol. 41, 931–933 (2021). PubMed PMC

Monk P. D., et al. ; Inhaled Interferon Beta COVID-19 Study Group, Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir. Med. 9, 196–206 (2021). PubMed PMC

Bastard P., et al. , Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine. J. Exp. Med. 218, e20202486 (2021). PubMed PMC

von Cube M., Timsit J. F., Schumacher M., Motschall E., Schumacher M., Quantification and interpretation of attributable mortality in core clinical infectious disease journals. Lancet Infect. Dis. 20, e299–e306 (2020). PubMed

Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency