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10.1126/science.abd4570

http://scihub22266oqcxt.onion/10.1126/science.abd4570
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32972995!7857407!32972995
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suck abstract from ncbi


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pmid32972995      Science 2020 ; 370 (6515): ä
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  • Inborn errors of type I IFN immunity in patients with life-threatening COVID-19 #MMPMID32972995
  • Zhang Q; Bastard P; Liu Z; Le Pen J; Moncada-Velez M; Chen J; Ogishi M; Sabli IKD; Hodeib S; Korol C; Rosain J; Bilguvar K; Ye J; Bolze A; Bigio B; Yang R; Arias AA; Zhou Q; Zhang Y; Onodi F; Korniotis S; Karpf L; Philippot Q; Chbihi M; Bonnet-Madin L; Dorgham K; Smith N; Schneider WM; Razooky BS; Hoffmann HH; Michailidis E; Moens L; Han JE; Lorenzo L; Bizien L; Meade P; Neehus AL; Ugurbil AC; Corneau A; Kerner G; Zhang P; Rapaport F; Seeleuthner Y; Manry J; Masson C; Schmitt Y; Schluter A; Le Voyer T; Khan T; Li J; Fellay J; Roussel L; Shahrooei M; Alosaimi MF; Mansouri D; Al-Saud H; Al-Mulla F; Almourfi F; Al-Muhsen SZ; Alsohime F; Al Turki S; Hasanato R; van de Beek D; Biondi A; Bettini LR; D'Angio' M; Bonfanti P; Imberti L; Sottini A; Paghera S; Quiros-Roldan E; Rossi C; Oler AJ; Tompkins MF; Alba C; Vandernoot I; Goffard JC; Smits G; Migeotte I; Haerynck F; Soler-Palacin P; Martin-Nalda A; Colobran R; Morange PE; Keles S; Colkesen F; Ozcelik T; Yasar KK; Senoglu S; Karabela SN; Rodriguez-Gallego C; Novelli G; Hraiech S; Tandjaoui-Lambiotte Y; Duval X; Laouenan C; Snow AL; Dalgard CL; Milner JD; Vinh DC; Mogensen TH; Marr N; Spaan AN; Boisson B; Boisson-Dupuis S; Bustamante J; Puel A; Ciancanelli MJ; Meyts I; Maniatis T; Soumelis V; Amara A; Nussenzweig M; Garcia-Sastre A; Krammer F; Pujol A; Duffy D; Lifton RP; Zhang SY; Gorochov G; Beziat V; Jouanguy E; Sancho-Shimizu V; Rice CM; Abel L; Notarangelo LD; Cobat A; Su HC; Casanova JL
  • Science 2020[Oct]; 370 (6515): ä PMID32972995show ga
  • 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.
  • |*Loss of Function Mutation[MESH]
  • |Adolescent[MESH]
  • |Adult[MESH]
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Alleles[MESH]
  • |Asymptomatic Infections[MESH]
  • |Betacoronavirus[MESH]
  • |COVID-19[MESH]
  • |Child[MESH]
  • |Child, Preschool[MESH]
  • |Coronavirus Infections/*genetics/*immunology[MESH]
  • |Female[MESH]
  • |Genetic Loci[MESH]
  • |Genetic Predisposition to Disease[MESH]
  • |Humans[MESH]
  • |Infant[MESH]
  • |Interferon Regulatory Factor-7/deficiency/genetics[MESH]
  • |Interferon Type I/*immunology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Pandemics[MESH]
  • |Pneumonia, Viral/*genetics/*immunology[MESH]
  • |Receptor, Interferon alpha-beta/deficiency/genetics[MESH]
  • |SARS-CoV-2[MESH]
  • |Toll-Like Receptor 3/deficiency/genetics[MESH]


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