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Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Scopus
Open Access Toplam 1.805 atıf DOI
Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
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Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection
Scopus
Havuzumuzda Open Access 8 atıf almış
Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.
Atıf Yapan Makale Bilgileri
Kurumlar (22)
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland
École Polytechnique Fédérale de Lausanne
Lausanne, Switzerland
Garvan Institute of Medical Research
Sydney, Australia
Helix OpCo LLC
San Diego, United States
Hôpital Bichat-Claude-Bernard AP-HP
Paris, France
Hôpital Necker Enfants Malades
Paris, France
Hôpital Universitaire Pitié Salpêtrière
Paris, France
Howard Hughes Medical Institute
Chevy Chase, United States
hVIVO Services Limited
London, United Kingdom
Imperial College London
London, United Kingdom