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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