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

(Science (New York, N.Y.), v370.6515)

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.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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TitleInborn errors of type I IFN immunity in patients with life-threatening COVID-19.
Date2020-10-23
Issue nameScience (New York, N.Y.)
Issue numberv370.6515
DOI10.1126/science.abd4570
PubMed32972995
AuthorsZhang 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, Schlüter 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, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ŞN, Rodríguez-Gallego C, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan 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, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton RP, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC & Casanova JL
InfoFoti G, Bellani G, Citerio G, Contro E, Pesci A, Valsecchi MG, Cazzaniga M, Abad J, Aguilera-Albesa S, Akcan OM, Darazam IA, Aldave JC, Ramos MA, Nadji SA, Alkan G, Allardet-Servent J, Allende LM, Alsina L, Alyanakian MA, Amador-Borrero B, Amoura Z, Antolí A, Arslan S, Assant S, Auguet T, Azot A, Bajolle F, Baldolli A, Ballester M, Feldman HB, Barrou B, Beurton A, Bilbao A, Blanchard-Rohner G, Blanco I, Blandinières A, Blazquez-Gamero D, Bloomfield M, Bolivar-Prados M, Borie R, Bosteels C, Bousfiha AA, Bouvattier C, Boyarchuk O, Bueno MRP, Bustamante J, Cáceres Agra JJ, Calimli S, Capra R, Carrabba M, Casasnovas C, Caseris M, Castelle M, Castelli F, de Vera MC, Castro MV, Catherinot E, Chalumeau M, Charbit B, Cheng MP, Clavé P, Clotet B, Codina A, Colkesen F, Çölkesen F, Colobran R, Comarmond C, Dalmau D, Darley DR, Dauby N, Dauger S, de Pontual L, Dehban A, Delplancq G, Demoule A, Diehl JL, Dobbelaere S, Durand S, Eldars W, Elgamal M, Elnagdy MH, Emiroglu M, Erdeniz EH, Aytekin SE, Euvrard R, Evcen R, Fabio G, Faivre L, Falck A, Fartoukh M, Faure M, Arquero MF, Flores C, Francois B, Fumadó V, Fusco F, Solis BG, Gaussem P, Gil-Herrera J, Gilardin L, Alarcon MG, Girona-Alarcón M, Goffard JC, Gok F, González-Montelongo R, Guerder A, Gul Y, Guner SN, Gut M, Hadjadj J, Haerynck F, Halwani R, Hammarström L, Hatipoglu N, Hernandez-Brito E, Heijmans C, Holanda-Peña MS, Horcajada JP, Hoste L, Hoste E, Hraiech S, Humbert L, Iglesias AD, Íñigo-Campos A, Jamme M, Arranz MJ, Jordan I, Jorens P, Kanat F, Kapakli H, Kara I, Karbuz A, Yasar KK, Keles S, Demirkol YK, Klocperk A, Król ZJ, Kuentz P, Kwan YWM, Lagier JC, Lambrecht BN, Lau YL, Le Bourgeois F, Leo YS, Lopez RL, Leung D, Levin M, Levy M, Lévy R, Li Z, Linglart A, Loeys B, Lorenzo-Salazar JM, Louapre C, Lubetzki C, Luyt CE, Lye DC, Mansouri D, Marjani M, Pereira JM, Martin A, Pueyo DM, Martinez-Picado J, Marzana I, Mathian A, Matos LRB, Matthews GV, Mayaux J, Mège JL, Melki I, Meritet JF, Metin O, Meyts I, Mezidi M, Migeotte I, Millereux M, Mirault T, Mircher C, Mirsaeidi M, Melián AM, Martinez AM, Morange P, Mordacq C, Morelle G, Mouly S, Muñoz-Barrera A, Naesens L, Nafati C, Neves JF, Ng LFP, Medina YN, Cuadros EN, Ocejo-Vinyals JG, Orbak Z, Oualha M, Özçelik T, Pan-Hammarström Q, Parizot C, Pascreau T, Paz-Artal E, Pellegrini S, de Diego RP, Philippe A, Philippot Q, Planas-Serra L, Ploin D, Poissy J, Poncelet G, Pouletty M, Quentric P, Raoult D, Rebillat AS, Reisli I, Ricart P, Richard JC, Rivet N, Rivière JG, Blanch GR, Rodrigo C, Rodriguez-Gallego C, Rodríguez-Palmero A, Romero CS, Rothenbuhler A, Rozenberg F, Ruiz Del Prado MY, Riera JS, Sanchez O, Sánchez-Ramón S, Schluter A, Schmidt M, Schweitzer CE, Scolari F, Sediva A, Seijo LM, Sene D, Senoglu S, Seppänen MRJ, Ilovich AS, Shahrooei M, Slabbynck H, Smadja DM, Sobh A, Moreno XS, Solé-Violán J, Soler C, Soler-Palacín P, Stepanovskiy Y, Stoclin A, Taccone F, Tandjaoui-Lambiotte Y, Taupin JL, Tavernier SJ, Terrier B, Thumerelle C, Tomasoni G, Toubiana J, Alvarez JT, Trouillet-Assant S, Troya J, Tucci A, Ursini MV, Uzunhan Y, Vabres P, Valencia-Ramos J, Van Braeckel E, Van de Velde S, Van Den Rym AM, Van Praet J, Vandernoot I, Vatansev H, Vélez-Santamaria V, Viel S, Vilain C, Vilaire ME, Vincent A, Voiriot G, Vuotto F, Yosunkaya A, Young BE, Yucel F, Zannad F, Zatz M, Belot A, Bole-Feysot C, Lyonnet S, Masson C, Nitschke P, Pouliet A, Schmitt Y, Tores F, Zarhrate M, Abel L, Andrejak C, Angoulvant F, Bachelet D, Basmaci R, Behillil S, Beluze M, Benkerrou D, Bhavsar K, Bompart F, Bouadma L, Bouscambert M, Caralp M, Cervantes-Gonzalez M, Chair A, Coelho A, Couffignal C, Couffin-Cadiergues S, D'Ortenzio E, Da Silveira C, Debray MP, Deplanque D, Descamps D, Desvallées M, Diallo A, Diouf A, Dorival C, Dubos F, Duval X, Eloy P, Enouf VV, Esperou H, Esposito-Farese M, Etienne M, Ettalhaoui N, Gault N, Gaymard A, Ghosn J, Gigante T, Gorenne I, Guedj J, Hoctin A, Hoffmann I, Jaafoura S, Kafif O, Kaguelidou F, Kali S, Khalil A, Khan C, Laouénan C, Laribi S, Le M, Le Hingrat Q, Le Mestre S, Le Nagard H, Lescure FX, Lévy Y, Levy-Marchal C, Lina B, Lingas G, Lucet JC, Malvy D, Mambert M, Mentré F, Mercier N, Meziane A, Mouquet H, Mullaert J, Neant N, Noret M, Pages J, Papadopoulos A, Paul C, Peiffer-Smadja N, Petrov-Sanchez V, Peytavin G, Picone O, Puéchal O, Rosa-Calatrava M, Rossignol B, Rossignol P, Roy C, Schneider M, Semaille C, Mohammed NS, Tagherset L, Tardivon C, Tellier MC, Téoulé F, Terrier O, Timsit JF, Trioux T, Tual C, Tubiana S, van der Werf S, Vanel N, Veislinger A, Visseaux B, Wiedemann A, Yazdanpanah Y, Alavoine L, Amat KKA, Behillil S, Bielicki J, Bruijning P, Burdet C, Caumes E, Charpentier C, Coignard B, Costa Y, Couffin-Cadiergues S, Damond F, Dechanet A, Delmas C, Descamps D, Duval X, Ecobichon JL, Enouf V, Espérou H, Frezouls W, Houhou N, Ilic-Habensus E, Kafif O, Kikoine J, Le Hingrat Q, Lebeaux D, Leclercq A, Lehacaut J, Letrou S, Lina B, Lucet JC, Malvy D, Manchon P, Mandic M, Meghadecha M, Motiejunaite J, Nouroudine M, Piquard V, Postolache A, Quintin C, Rexach J, Roufai L, Terzian Z, Thy M, Tubiana S, van der Werf S, Vignali V, Visseaux B, Yazdanpanah Y, van Agtmael M, Algera AG, van Baarle F, Bax D, Beudel M, Bogaard HJ, Bomers M, Bos L, Botta M, de Brabander J, de Bree G, Brouwer MC, de Bruin S, Bugiani M, Bulle E, Chouchane O, Cloherty A, Elbers P, Fleuren L, Geerlings S, Geerts B, Geijtenbeek T, Girbes A, Goorhuis B, Grobusch MP, Hafkamp F, Hagens L, Hamann J, Harris V, Hemke R, Hermans SM, Heunks L, Hollmann MW, Horn J, Hovius JW, de Jong MD, Koning R, van Mourik N, Nellen J, Paulus F, Peters E, van der Poll T, Preckel B, Prins JM, Raasveld J, Reijnders T, Schinkel M, Schultz MJ, Schuurman A, Sigaloff K, Smit M, Stijnis CS, Stilma W, Teunissen C, Thoral P, Tsonas A, van der Valk M, Veelo D, Vlaar APJ, de Vries H, van Vugt M, Wiersinga WJ, Wouters D, Zwinderman AHK, van de Beek D, Abel L, Aiuti A, Al Muhsen S, Al-Mulla F, Anderson MS, Arias AA, Feldman HB, Bogunovic D, Bolze A, Bondarenko A, Bousfiha AA, Brodin P, Bryceson Y, Bustamante CD, Butte M, Casari G, Chakravorty S, Christodoulou J, Cirulli E, Condino-Neto A, Cooper MA, Dalgard CL, David A, DeRisi JL, Desai M, Drolet BA, Espinosa S, Fellay J, Flores C, Franco JL, Gregersen PK, Haerynck F, Hagin D, Halwani R, Heath J, Henrickson SE, Hsieh E, Imai K, Itan Y, Karamitros T, Kisand K, Ku CL, Lau YL, Ling Y, Lucas CL, Maniatis T, Mansouri D, Marodi L, Meyts I, Milner J, Mironska K, Mogensen T, Morio T, Ng LFP, Notarangelo LD, Novelli A, Novelli G, O'Farrelly C, Okada S, Ozcelik T, de Diego RP, Planas AM, Prando C, Pujol A, Quintana-Murci L, Renia L, Renieri A, Rodríguez-Gallego C, Sancho-Shimizu V, Sankaran V, Barrett KS, Shahrooei M, Snow A, Soler-Palacín P, Spaan AN, Tangye S, Turvey S, Uddin F, Uddin MJ, van de Beek D, Vazquez SE, Vinh DC, von Bernuth H, Washington N, Zawadzki P, Su HC, Casanova JL, Jing H, Tung W, Luthers CR, Bauman BM, Shafer S, Zheng L, Zhang Z, Kubo S, Chauvin SD, Meguro K, Shaw E, Lenardo M, Lack J, Karlins E, Hupalo DM, Rosenberger J, Sukumar G, Wilkerson MD, Zhang X
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