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[키워드] a minor acute respiratory syndrome acute respiratory syndrome coronavirus acute respiratory syndrome coronavirus 2 administration Affect affecting age amplification amplification pathway Asymptomatic autoantibodies autoantibody autoantibody system autosomal-dominant autosomal-recessive Beck biochemically BOLD candidate gene approach caused cellular clinical Clinical course Clinical outcome clinical variability complete penetrance complex component components core gene core genes coronavirus coronavirus disease Coronavirus disease 2019 Course COVID COVID Human Genetic Effort COVID-19 COVID-19 patient COVID-19 pneumonia Critical Critical disease cytokine Cytokines damage dampen deficiencies deficiency defined Deleterious dendritic cell dendritic cells determine Diseases double-stranded RNA eight enrichment epidemiological studies Exome fibroblast fibroblasts Genes genes encoding genetic defect genetic defects genetics Genome genomics study had milder phenotype healthy individuals highest Hospitalized Human human fibroblasts with mutations Hypothesis identify IFN IFN response IFN-α2 IFNAR1 IFNAR1 deficiency IFNAR2 IFNs IKBKG immune system Immunity immunological in healthy individuals in some in vitro Inborn error Inborn errors incomplete penetrance individual induction pathway Infection infection with SARS-CoV-2 Infectious diseases Influenza influenza pneumonia Influenza virus inheritance interferon interferon regulatory factor interferon regulatory factor 7 interferons interferons (IFNs) involved IRF3 IRF7 IRF9 lack life-threatening likelihood loci LOF loss-of-function male mechanism Medical conditions minor minor allele frequency molecular molecule molecules monogenic inborn error monogenic inborn errors mutated Mutation NEMO NEMO/IKBKG Neutralizing nonsynonymous variant other variants outcome pathogen pathogen-induced inflammation pathway Patient patients Perspective plasmacytoid dendritic cells pLOF Pneumonia predicted Prevent produced rare variant Rare variants Regulation respiratory reveal risk risk factor SARS-CoV-2 SARS-COV-2 infection SARS-CoV-2 infection in vitro Science selected sequenced severe acute respiratory syndrome Coronavirus severe acute respiratory syndrome coronavirus 2 severe coronavirus disease severe COVID-19 Severe COVID-19 pneumonia severe disease Severe infection silent infection Stat1 STAT2 subject susceptible TBK1 tested Therapeutic benefit this system TICAM1 TICAM1/TRIF tissue TLR3 Toll-like receptor Toll-like receptor 3 TRAF3 TRIF Type type I Type I IFN type I IFNs type I interferon UNC93B1 underlie variant variants Viral Viral illness viral illnesses
[DOI] 10.1126/science.abd4570 PMC 바로가기 [Article Type] Research Article