Autoantibodies neutralizing type I IFNs are present in similar to 4% of uninfected individuals over 70 years old and account for similar to 20% of COVID-19 deaths

Author(s):Show less -

Bastard, Paul ^{[1, 2, 3]} ; Gervais, Adrian ^{[1, 2]} ; Le Voyer, Tom ^{[1, 2]} ; Rosain, Jeremie ^{[1, 2]} ; Philippot, Quentin ^{[1, 2]} ; Manry, Jeremy ^{[1, 2]} ; Michailidis, Eleftherios ^[4] ; Hoffmann, Hans-Heinrich ^[4] ; Eto, Shohei ^[5] ; Garcia-Prat, Marina ^[6] ; Bizien, Lucy ^{[1, 2]} ; Parra-Martinez, Alba ^[6] ; Yang, Rui ^[3] ; Haljasmagi, Liis ^[7] ; Migaud, Melanie ^{[1, 2]} ; Sarekannu, Karita ^[7] ; Maslovskaja, Julia ^[7] ; de Prost, Nicolas ^{[8, 9]} ; Tandjaoui-Lambiotte, Yacine ^[10] ; Luyt, Charles-Edouard ^{[11, 12]} ; Amador-Borrero, Blanca ^[13] ; Gaudet, Alexandre ^{[14, 15, 16, 17, 18]} ; Poissy, Julien ^{[14, 15, 16, 17, 18]} ; Morel, Pascal ^{[19, 20]} ; Richard, Pascale ^[19] ; Cognasse, Fabrice ^{[21, 22]} ; Troya, Jesus ^[23] ; Trouillet-Assant, Sophie ^{[24, 25, 26]} ; Belot, Alexandre ^{[24, 25, 27, 28]} ; Saker, Kahina ^{[24, 25]} ; Garcon, Pierre ^[29] ; Riviere, Jacques G. ^[6] ; Lagier, Jean-Christophe ^{[30, 31]} ; Gentile, Stephanie ^{[32, 33]} ; Rosen, Lindsey B. ^[34] ; Shaw, Elana ^[34] ; Morio, Tomohiro ^[35] ; Tanaka, Junko ^[36] ; Dalmau, David ^{[37, 38, 39]} ; Tharaux, Pierre-Louis ^[40] ; Sene, Damien ^[13] ; Stepanian, Alain ^{[41, 42]} ; Megarbane, Bruno ^[43] ; Triantafyllia, Vasiliki ^[44] ; Fekkar, Arnaud ^{[2, 45]} ; Heath, James R. ^[46] ; Franco, Jose Luis ^[47] ; Anaya, Juan-Manuel ^[48] ; Sole-Violan, Jordi ^{[49, 50]} ; Imberti, Luisa ^[51] ; Biondi, Andrea ^{[52, 53]} ; Bonfanti, Paolo ^[54] ; Castagnoli, Riccardo ^{[34, 55]} ; Delmonte, Ottavia M. ^[34] ; Zhang, Yu ^{[34, 56]} ; Snow, Andrew L. ^[57] ; Holland, Steven M. ^[34] ; Biggs, Catherine M. ^[58] ; Moncada-Velez, Marcela ^[3] ; Arias, Andres Augusto ^{[59, 3, 60]} ; Lorenzo, Lazaro ^{[1, 2]} ; Boucherit, Soraya ^{[1, 2]} ; Coulibaly, Boubacar ^{[1, 2]} ; Anglicheau, Dany ^{[61, 62]} ; Planas, Anna M. ^{[63, 64]} ; Haerynck, Filomeen ^[65] ; Duvlis, Sotirija ^{[66, 67]} ; Nussbaum, Robert L. ^[68] ; Ozcelik, Tayfun ^[69] ; Keles, Sevgi ^[70] ; Bousfiha, Ahmed A. ^{[71, 72]} ; El Bakkouri, Jalila ^{[71, 72]} ; Ramirez-Santana, Carolina ^{[47, 48]} ; Paul, Stephane ^[73] ; Pan-Hammarstrom, Qiang ^[74] ; Hammarstrom, Lennart ^[74] ; Dupont, Annabelle ^[75] ; Kurolap, Alina ^[76] ; Metz, Christine N. ^[77] ; Aiuti, Alessandro ^{[78, 79]} ; Casari, Giorgio ^{[78, 79]} ; Lampasona, Vito ^[80] ; Ciceri, Fabio ^[81] ; Barreiros, Lucila A. ^[82] ; Dominguez-Garrido, Elena ^[83] ; Vidigal, Mateus ^[84] ; Zatz, Mayana ^[84] ; van de Beek, Diederik ^[85] ; Sahanic, Sabina ^[86] ; Tancevski, Ivan ^[86] ; Stepanovskyy, Yurii ^[87] ; Boyarchuk, Oksana ^[88] ; Nukui, Yoko ^[89] ; Tsumura, Miyuki ^[5] ; Vidaur, Loreto ^{[90, 91]} ; Tangye, Stuart G. ^{[92, 93]} ; Burrel, Sonia ^[94] ; Duffy, Darragh ^[95] ; Quintana-Murci, Lluis ^{[96, 97]} ; Klocperk, Adam ^{[98, 99]} ; Kann, Nelli Y. ^[100] ; Shcherbina, Anna ^[100] ; Lau, Yu-Lung ^[101] ; Leung, Daniel ^[101] ; Coulongeat, Matthieu ^[102] ; Marlet, Julien ^{[103, 104]} ; Koning, Rutger ^[85] ; Reyes, Luis Felipe ^{[105, 106]} ; Chauvineau-Grenier, Angelique ^[107] ; Venet, Fabienne ^{[108, 109, 110]} ; Monneret, Guillaume ^{[108, 110]} ; Nussenzweig, Michel C. ^{[111, 112]} ; Arrestier, Romain ^{[8, 9]} ; Boudhabhay, Idris ^{[61, 62]} ; Baris-Feldman, Hagit ^{[113, 76]} ; Hagin, David ^{[113, 114]} ; Wauters, Joost ^[115] ; Meyts, Isabelle ^{[116, 117]} ; Dyer, Adam H. ^{[118, 119]} ; Kennelly, Sean P. ^{[118, 119]} ; Bourke, Nollaig M. ^[119] ; Halwani, Rabih ^[120] ; Sharif-Askari, Narjes Saheb ^[120] ; Dorgham, Karim ^[121] ; Sallette, Jerome ^[122] ; Sedkaoui, Souad Mehlal ^[122] ; AlKhater, Suzan ^{[123, 124]} ; Rigo-Bonnin, Raul ^[125] ; Morandeira, Francisco ^[126] ; Roussel, Lucie ^{[127, 128]} ; Vinh, Donald C. ^{[127, 128]} ; Ostrowski, Sisse Rye ^[129] ; Condino-Neto, Antonio ^[82] ; Prando, Carolina ^[130] ; Bondarenko, Anastasiia ^[87] ; Spaan, Andras N. ^{[131, 3]} ; Gilardin, Laurent ^{[132, 133]} ; Fellay, Jacques ^{[134, 135, 136, 137]} ; Lyonnet, Stanislas ^[138] ; Bilguvar, Kaya ^{[139, 140, 141, 142]} ; Lifton, Richard P. ^{[139, 140, 143]} ; Mane, Shrikant ^[139] ; Anderson, Mark S. ^[144] ; Boisson, Bertrand ^{[1, 2, 3]} ; Beziat, Vivien ^{[1, 2, 3]} ; Zhang, Shen-Ying ^{[1, 2, 3]} ; Andreakos, Evangelos ^[44] ; Hermine, Olivier ^{[1, 145]} ; Pujol, Aurora ^{[146, 147]} ; Peterson, Part ^[7] ; Mogensen, Trine H. ^{[148, 149]} ; Rowen, Lee ^[46] ; Mond, James ^[150] ; Debette, Stephanie ^{[151, 152]} ; de Lamballerie, Xavier ^[153] ; Duval, Xavier ^{[154, 155, 156, 157]} ; Mentre, France ^{[154, 155, 156]} ; Zins, Marie ^[158] ; Soler-Palacin, Pere ^[6] ; Colobran, Roger ^[159] ; Gorochov, Guy ^{[121, 160]} ; Solanich, Xavier ^[161] ; Susen, Sophie ^[75] ; Martinez-Picado, Javier ^{[162, 163, 164, 165]} ; Raoult, Didier ^{[30, 31]} ; Vasse, Marc ^{[166, 167]} ; Gregersen, Peter K. ^[77] ; Piemonti, Lorenzo ^[80] ; Rodriguez-Gallego, Carlos ^{[168, 169]} ; Notarangelo, Luigi D. ^[34] ; Su, Helen C. ^{[34, 170]} ; Kisand, Kai ^[7] ; Okada, Satoshi ^[5] ; Puel, Anne ^{[1, 2, 3]} ; Jouanguy, Emmanuelle ^{[1, 2, 3]} ; Rice, Charles M. ^[4] ; Tiberghien, Pierre ^{[19, 20]} ; Zhang, Qian ^{[1, 2, 3]} ; Cobat, Aurelie ^{[1, 2, 3]} ; Abel, Laurent ^{[1, 2, 3]} ; Casanova, Jean-Laurent ^{[112, 1, 2, 3]} ; Lab, HGID ; Clinicians, COVID ; Clinicians, COVID-STORM ; Grp, NIAID Immune Response Covid ; Grp, NH-COVAIR Study ; CHGE, Danish ; Study, Danish Blood Donor ; Interest, St Jamess Hosp Sars CoV2 ; Grp, French COVID Cohort Study ; COVID-Grp, Imagine ; Consortium, Milieu Interieur ; Cohort, CoV-Contact ; Inv, Amsterdam Umc Covid-19 Biobank ; Efft, COVID Human Genetic ; Cohort, CONSTANCES ; Study, 3C-Dijon ; HealthCare, Cerba ; Grp, Etab Sang Study

Affiliation:Show less -

^[1] Univ Paris, Imagine Inst, Paris - France

^[2] Necker Hosp Sick Children, INSERM U1163, Necker Branch, Lab Human Genet Infect Dis, Paris - France

^[3] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 - USA

^[4] Rockefeller Univ, Lab Virol & Infect Dis, 1230 York Ave, New York, NY 10021 - USA

^[5] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Pediat, Hiroshima - Japan

^[6] Univ Autonoma Barcelona UAB, Vall dHebron Res Inst, Hosp Univ Vall dHebron, Pediat Infect Dis & Immunodeficiencies Unit, Vall dHebron Barcelona Hosp Campus, Barcelona, Catalonia - Spain

^[7] Univ Tartu, Inst Biomed & Translat Med, Tartu - Estonia

^[8] Hop Univ Henri Mondor, Assistance Publ Hop Paris AP HP, Serv Med Intens Reanimat, Paris - France

^[9] Univ Paris Est Creteil, Fac Sante Creteil, Grp Rech Clin CARMAS, 51 Ave Marechal de Lattre de Tassigny, F-94010 Creteil - France

^[10] Avicenne Hosp, AP HP, INSERM U1272, Hypoxia & Lung, Bobigny - France

^[11] Sorbonne Univ, Hop Pitie Salpetriere, AP HP, Med Intens Reanimat, Paris - France

^[12] INSERM UMRS 1166 iCAN, Inst Cardiometab & Nutr, Paris - France

^[13] Paris Univ, Lariboisiere Hosp, AP HP, Internal Med Dept, Paris - France

^[14] Inst Pasteur, Lille - France

^[15] Univ Lille, U1019 UMR9017, Ctr Infect & Immun Lille, Lille - France

^[16] CNRS, UMR9017, Lille - France

^[17] INSERM U1019, Lille - France

^[18] CHU Lille, Pole Reanimat, Hop Roger Salengro Lille, Lille - France

^[19] Etab Francais Sang, La Plaine St Denis - France

^[20] Univ Franche Comte, EFS, INSERM, UMR1098 RIGHT, Besancon - France

^[21] Univ Jean Monnet St Etienne, Univ Lyon, SAINBIOSE, INSERM U1059, St Etienne - France

^[22] Etab Francais Sang, St Etienne - France

^[23] Infanta Leonor Univ Hosp, Dept Internal Med, Madrid - Spain

^[24] Hosp Civils Lyon, Lyon - France

^[25] Lyon Univ, Int Ctr Res Infectiol, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon - France

^[26] Lyon Sud Hosp, Hosp Civils Lyon, Hosp Civils Lyon BioMerieux, Joint Res Unit, Pierre Benite - France

^[27] Natl Referee Ctr Rheumat & Autoimmune & Syst Dis, Lyon - France

^[28] Hosp Civils Lyon, Immunopathol Federat LIFE, Lyon - France

^[29] Grand Hop Est Francilien, Site Marne La Vallee, Intens Care Unit, Jossigny - France

^[30] Inst Hosp Univ Mediterranee Infect, Marseille - France

^[31] Aix Marseille Univ, IRD, Assistance Publ Hop Marseille APHM, MEPHI, Marseille - France

^[32] Hop Univ Marseille, AP HM, Serv Evaluat Med, Marseille - France

^[33] Aix Marseille Univ, Sch Med, EA 3279, CEReSS Hlth Serv Res & Qual Life Ctr, La Timone Med Campus, Marseille - France

^[34] NIAID, Lab Clin Immunol & Microbiol, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 - USA

^[35] Tokyo Med & Dent Univ TMDU, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Tokyo - Japan

^[36] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Epidemiol Infect Dis Control & Prevent, Hiroshima - Japan

^[37] Univ Barcelona, Barcelona - Spain

^[38] Hosp Univ Mutua Terrassa, Terrassa - Spain

^[39] Fundacio Docencia & Recerca MutuaTerrassa, Terrassa - Spain

^[40] Univ Paris, Paris Cardiovasc Res Ctr, PARCC, INSERM, Paris - France

^[41] Univ Paris Diderot, Hop Lariboisiere, AP HP, Serv Hematol Biol, Paris - France

^[42] Univ Paris Diderot, Inst Univ Hematol Hop St Louis, EA3518, Paris - France

^[43] Univ Paris Diderot, Hop Lariboisiere, AP HP, Reanimat Med & Toxicol, INSERM, Unite Mixte Rech Sc, Paris - France

^[44] Acad Athens, Biomed Res Fdn, Ctr Clin Expt Surg & Translat Res, Lab Immunobiol, Athens 11527 - Greece

^[45] Grp Hosp Pitie Salpetriere, AP HP, Serv Parasitol Mycol, Paris - France

^[46] Inst Syst Biol, Seattle, WA - USA

^[47] Univ Antioquia UdeA, Sch Med, Dept Microbiol & Parasitol, Primary Immunodeficiencies Grp, Medellin - Colombia

^[48] Univ Rosario, Sch Med & Hlth Sci, Ctr Autoimmune Dis Res, Bogota - Colombia

^[49] Univ Hosp Gran Canaria Dr Negrin, Canarian Hlth Syst, Intens Care Med, Las Palmas Gran Canaria, Canary Islands - Spain

^[50] Inst Salud Carlos III, CIBER Enfermedades Resp CIBERES, Madrid - Spain

^[51] ASST Spedali Civili Brescia, Diagnost Dept, CREA Lab, Brescia - Italy

^[52] Univ Milano Bicocca, Fdn MBBM, Osped San Gerardo, EuroBloodNet, MetabERN, Pediat Dept, Monza - Italy

^[53] Univ Milano Bicocca, Fdn MBBM, Osped San Gerardo, EuroBloodNet, MetabERN, Ctr Tettamanti European Reference Network PaedCan, Monza - Italy

^[54] Univ Milano Bicocca, San Gerardo Hosp, Dept Infect Dis, Monza - Italy

^[55] Univ Pavia, Fdn IRCCS Policlin San Matteo, Dept Pediat, Pavia - Italy

^[56] NIAID, Clin Genom Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 - USA

^[57] Uniformed Serv Univ Hlth Sci, Dept Pharmacol & Mol Therapeut, Bethesda, MD 20814 - USA

^[58] Univ British Columbia, British Columbia Childrens Hosp, Dept Pediat, Vancouver, BC - Canada

^[59] Univ Antioquia UdeA, Sch Microbiol, Medellin - Colombia

^[60] Univ Antioquia UdeA, Primary Immunodeficiencies Grp, Medellin - Colombia

^[61] Necker Univ Hosp, AP HP, Dept Nephrol & Transplantat, Paris - France

^[62] Paris Univ, INSERM U1151 CNRS UMR 8253, INEM, Paris - France

^[63] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona - Spain

^[64] CSIC, Inst Biomed Res IIBB, Barcelona - Spain

^[65] Ghent Univ Hosp, Ctr Primary Immunodeficiency Ghent, Jeffrey Modell Diag & Res Ctr, Dept Paediat Immunol & Pulmonol, Ghent - Belgium

^[66] Univ Goce Delchev, Fac Med Sci, Stip - North Macedonia

^[67] Inst Publ Hlth Republ North Macedonia, Skopje - North Macedonia

^[68] Univ Calif San Francisco, Canc Genet & Prevent Program, San Francisco, CA 94143 - USA

^[69] Bilkent Univ, Dept Mol Biol & Genet, Ankara - Turkey

^[70] Necmettin Erbakan Univ, Meram Fac Med, Konya - Turkey

^[71] Hassan II Univ, CHU Ibn Rushd, Dept Pediat Infect Dis, Clin Immunol Unit, Casablanca - Morocco

^[72] Hassan II Univ, Fac Med & Pharm, Lab Immunol Clin Inflammat & Allergie, LICIA, Casablanca - Morocco

^[73] Univ Hosp St Etienne, GIMAP Ctr Int Rech Infectiol CIRI INSERM U1111, CIC1408, Dept Immunol, St Etienne - France

^[74] Karolinska Inst, Dept Biosci & Nutr, Stockholm - Sweden

^[75] Univ Lille, INSERM, CHU Lille, Inst Pasteur Lille, U1011 EGID, F-59000 Lille - France

^[76] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Genet Inst, Tel Aviv - Israel

^[77] Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY - USA

^[78] Univ Vita Salute San Raffaele, Milan - Italy

^[79] IRCCS Osped San Raffaele, Clin Genom, Milan - Italy

^[80] IRCCS San Raffaele Sci Inst, Diabet Res Inst, Milan - Italy

^[81] IRCCS San Raffaele Sci Inst, Hematol & Bone Marrow Transplantat Unit, Milan - Italy

^[82] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[83] Ctr Invest Biomed La Rioja, Fdn Rioja Salud, Logrono - Spain

^[84] Univ Sao Paulo, Sao Paulo - Brazil

^[85] Amsterdam Neurosci, Dept Neurol, Amsterdam - Netherlands

^[86] Med Univ Innsbruck, Dept Internal Med 2, Innsbruck - Austria

^[87] Shupyk Natl Healthcare Univ Ukraine, Kiev - Ukraine

^[88] I Horbachevsky Ternopil Natl Med Univ, Dept Childrens Dis & Pediat Surg, Ternopol - Ukraine

^[89] TMDU, Med Hosp, Dept Infect Control & Prevent, Tokyo - Japan

^[90] Inst Salud Carlos III, CIBERES, Madrid - Spain

^[91] Donostia Univ Hosp, Biodonostia Inst Donostia, Intens Care Med, San Sebastian - Spain

^[92] Garvan Inst Med Res, Sydney, NSW - Australia

^[93] UNSW Sydney, Fac Med & Hlth, St Vincents Clin Sch, Sydney, NSW - Australia

^[94] Sorbonne Univ, INSERM U1136, Inst Pierre Louis Epidemiol & Sante Publ iPLESP, Hop Pitie Salpetriere, AP HP, Serv Virol, Paris - France

^[95] Inst Pasteur, Translat Immunol Lab, Paris - France

^[96] Inst Pasteur, Human Evolutionary Genet Unit, CNRS UMR 2000, Paris - France

^[97] Coll France, Chair Human Genom & Evolut, Paris - France

^[98] Univ Hosp Motol, Prague - Czech Republic

^[99] Charles Univ Prague, Fac Med 2, Dept Immunol, Prague - Czech Republic

^[100] Dmitry Rogachev Natl Med Res Ctr Pediat Hematol O, Moscow - Russia

^[101] Univ Hong Kong, Dept Paediat & Adolescent Med, Hong Kong - Peoples R China

^[102] Tours Univ Med Ctr, Div Geriatr Med, Tours - France

^[103] Univ Tours, MAVIVH, INSERM U1259, Tours - France

^[104] CHU Tours, Serv Bacteriol Virol & Hyg Hosp, Tours - France

^[105] Univ La Sabana, Dept Microbiol, Chia - Colombia

^[106] Clin Univ La Sabana, Dept Crit Care Med, Chia - Colombia

^[107] CHI Robert Ballanger, Serv Biol Med, Aulnay Sous Bois - France

^[108] Hosp Civils Lyon, Lab Immunol, Hop Edouard Herriot, Lyon - France

^[109] Univ Claude Bernard Lyon 1, Ecole Normale Super Lyon, UMR5308, CIRI, INSERM U1111, CNRS, Lyon - France

^[110] Univ Claude Bernard Lyon 1, Hosp Civils Lyon, Hop Edouard Herriot BioMerieux, EA 7426, Pathophysiol Injury Induced Immunosuppres, Lyon - France

^[111] Rockefeller Univ, Lab Mol Immunol, 1230 York Ave, New York, NY 10021 - USA

^[112] Howard Hughes Med Inst, New York, NY 10065 - USA

^[113] Tel Aviv Univ, Sackler Fac Med, Tel Aviv - Israel

^[114] Tel Aviv Sourasky Med Ctr, Dept Med, Allergy & Clin Immunol Unit, Tel Aviv - Israel

^[115] Univ Hosp Leuven, Med Intens Care Unit, Leuven - Belgium

^[116] Katholieke Univ Leuven, Lab Inborn Errors Immun, Dept Microbiol Immunol & Transplantat, Leuven - Belgium

^[117] Univ Hosp Leuven, Jeffrey Modell Diagnost & Res Network Ctr, Dept Pediat, Leuven - Belgium

^[118] Tallaght Univ Hosp, Dept Age Related Healthcare, Dublin - Ireland

^[119] Trinity Coll Dublin, Sch Med, Dept Med Gerontol, Dublin - Ireland

^[120] Univ Sharjah, Coll Med, Sharjah Inst Med Res, Sharjah - U Arab Emirates

^[121] Sorbonne Univ, Ctr Immunol & Malad Infect, CIMI Paris, INSERM, Paris - France

^[122] Cerba HealthCare, Issy Les Moulineaux - France

^[123] King Fahad Hosp Univ, Dept Pediat, Al Khobar - Saudi Arabia

^[124] Imam Abdulrahman Bin Faisal Univ, Coll Med, Dammam - Saudi Arabia

^[125] Hosp Univ Bellvitge, Dept Clin Lab, IDIBELL, Barcelona - Spain

^[126] Hosp Univ Bellvitge, Dept Immunol, IDIBELL, Barcelona - Spain

^[127] McGill Univ Hlth Ctr, Dept Med, Div Infect Dis, Montreal, PQ - Canada

^[128] McGill Univ Hlth Ctr, Res Inst, Infect Dis Susceptibil Program, Montreal, PQ - Canada

^[129] Copenhagen Univ Hosp, Rishosp, Dept Clin Immunol, Copenhagen - Denmark

^[130] Inst Pesquisa Pele Pequeno Principe, Fac Pequeno Principe, Curitiba, Parana - Brazil

^[131] Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht - Netherlands

^[132] Hop Univ Jean Verdier, AP HP, Serv Med Interne, Bondy - France

^[133] Ctr Rech Cordeliers, INSERM U1138, Paris - France

^[134] Swiss Inst Bioinformat, Lausanne - Switzerland

^[135] Univ Lausanne, Lausanne - Switzerland

^[136] Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne - Switzerland

^[137] Lausanne Univ Hosp, Precis Med Unit, Lausanne - Switzerland

^[138] Univ Paris, Imagine Inst, INSERM UMR 1163, Paris - France

^[139] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 - USA

^[140] Yale Sch Med, Yale Ctr Genome Anal, New Haven, CT - USA

^[141] Yale Univ, Dept Neurosurg, Sch Med, New Haven, CT - USA

^[142] Acibadem Univ, Dept Med Genet, Sch Med, Istanbul - Turkey

^[143] Rockefeller Univ, Lab Human Genet & Genom, 1230 York Ave, New York, NY 10021 - USA

^[144] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 - USA

^[145] Hop Necker Enfants Malad, AP HP, Dept Hematol, Paris - France

^[146] Catalan Inst Res & Adv Studies ICREA, Barcelona - Spain

^[147] Hosp Duran & Reynals, IDIBELL, Neurometab Dis Lab, CIBERER U759, Barcelona - Spain

^[148] Aarhus Univ, Dept Biomed, Aarhus - Denmark

^[149] Aarhus Univ Hosp, Dept Infect Dis, Aarhus - Denmark

^[150] ADMA Biol Inc, Ramsey, NJ - USA

^[151] Univ Bordeaux, Bordeaux Populat Hlth Ctr, UMR1219, INSERM, F-33000 Bordeaux - France

^[152] Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, F-33000 Bordeaux - France

^[153] UVE Aix Marseille Univ, Unite Virus Emergents, IHU Mediterranee Infect, IRD 190, INSERM 1207, Marseille - France

^[154] INSERM CIC 1425, Paris - France

^[155] Univ Paris, INSERM, IAME UMR S 1137, Paris - France

^[156] Hop Bichat Claude Bernard, AP HP, Dept Epidemiol Biostat & Rech Clin, Paris - France

^[157] Bichat Claude Bernard Hosp, AP HP, Infect & Trop Dis Dept, Paris - France

^[158] Univ Paris, Univ Paris Saclay, INSERM UMS11, UVSQ, Villejuif - France

^[159] Hosp Univ Vall dHebron, Vall dHebron Res Inst, Genet Dept, Immunol Div, Vall dHebron Barcelona Hosp Campus, Barcelona, Catalonia - Spain

^[160] Hop La Pitie Salpetriere, AP HP, Dept Immunol, Paris - France

^[161] Hosp Univ Bellvitge, Dept Internal Med, IDIBELL, Barcelona - Spain

^[162] IrsiCaixa AIDS Res Inst, Badalona - Spain

^[163] Inst Hlth Sci Res Germans Trias & Pujol IGTP, Badalona - Spain

^[164] Univ Vic Cent Univ Catalonia UVic UCC, Fac Med, Ctr Hlth & Social Care Res CESS, Infect Dis & Immun, Vic - Spain

^[165] Catalan ICREA, Barcelona - Spain

^[166] Hop Foch, Serv Biol Clin, Suresnes - France

^[167] Hop Foch, UMR S 1176, Suresnes - France

^[168] Univ Hosp Gran Canaria Dr Negrin, Canarian Hlth Syst, Dept Immunol, Las Palmas Gran Canaria - Spain

^[169] Univ Fernando Pessoa Canarias, Dept Clin Sci, Las Palmas Gran Canaria - Spain

^[170] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA - USA

• Document type: Journal article
• Source: SCIENCE IMMUNOLOGY; v. 6, n. 62 AUG 2021.
• Web of Science Citations: 7

Abstract

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases. (AU)

• FAPESP's process: 20/09702-1 - Study of protective genetic variants in resilient nonagenarians and centenarians
• Grantee: Mateus Vidigal de Castro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral