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

Male 0301 basic medicine Coronaviruses COVID19 [SDV]Life Sciences [q-bio] Interferon Regulatory Factor-7 NF-KAPPA-B 32 Biomedical and Clinical Sciences Receptor, Interferon alpha-beta SUSCEPTIBILITY Settore MED/03 - GENETICA MEDICA Interferon alpha-beta CoV-Contact Cohort Coronaviruses Therapeutics and Interventions [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Loss of Function Mutation 80 and over Medicine and Health Sciences 2.1 Biological and endogenous factors Asymptomatic Infection Viral Imagine COVID Group Child 3202 Clinical Sciences Lung Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Asymptomatic Infections; Betacoronavirus; COVID-19; Child; Child, Preschool; Coronavirus Infections/genetics; Coronavirus Infections/immunology; Female; Genetic Loci; Genetic Predisposition to Disease; Humans; Infant; Interferon Regulatory Factor-7/deficiency; Interferon Regulatory Factor-7/genetics; Interferon Type I/immunology; Loss of Function Mutation; Male; Middle Aged; Pandemics; Pneumonia, Viral/genetics; Pneumonia, Viral/immunology; Receptor, Interferon alpha-beta/deficiency; Receptor, Interferon alpha-beta/genetics; SARS-CoV-2; Toll-Like Receptor 3/deficiency; Toll-Like Receptor 3/genetics; Young Adult Asymptomatic Infections Research Articles Allele Aged, 80 and over 0303 health sciences Multidisciplinary COVID Clinicians 3 Good Health and Well Being Middle Aged 3. Good health DEFICIENCY [SDV] Life Sciences [q-bio] Infectious Diseases Child, Preschool Interferon Type I Pneumonia & Influenza [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases Female Infection Coronavirus Infections Human Receptor NIAID-USUHS Adult Adolescent HERPES-SIMPLEX ENCEPHALITIS General Science & Technology French COVID Cohort Study Group Pneumonia, Viral 610 Young Adult Betacoronavirus 03 medical and health sciences Genetics Humans Genetic Predisposition to Disease Preschool COVID Human Genetic Effort Pandemics Alleles Biobank Aged Betacoronaviru Pandemic Coronavirus Infection SARS-CoV-2 Inflammatory and immune system TAGC COVID Immunity Group Médecine pathologie humaine COVID-19 Infant Pneumonia Amsterdam UMC Covid-19 Influenza COVID-STORM Clinicians Toll-Like Receptor 3 Emerging Infectious Diseases Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Asymptomatic Infections; Betacoronavirus; COVID-19; Child; Child, Preschool; Coronavirus Infections; Female; Genetic Loci; Genetic Predisposition to Disease; Humans; Infant; Interferon Regulatory Factor-7; Interferon Type I; Male; Middle Aged; Pandemics; Pneumonia, Viral; Receptor, Interferon alpha-beta; SARS-CoV-2; Toll-Like Receptor 3; Young Adult; Loss of Function Mutation Genetic Loci
DOI: 10.1126/science.abd4570 Publication Date: 2020-09-24T23:13:31Z
AUTHORS (748)
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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