Abstract
SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.
Original language | English |
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Journal | Research square |
DOIs | |
Publication status | Published - 14 Jan 2022 |
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In: Research square, 14.01.2022.
Research output: Contribution to journal › Article › Academic
TY - JOUR
T1 - The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies
AU - Manry, Jeremy
AU - Bastard, Paul
AU - Gervais, Adrian
AU - Voyer, Tom Le
AU - Rosain, Jérémie
AU - Philippot, Quentin
AU - Michailidis, Eleftherios
AU - Hoffmann, Hans-Heinrich
AU - Eto, Shohei
AU - Garcia-Prat, Marina
AU - Bizien, Lucy
AU - Parra-Martínez, Alba
AU - Yang, Rui
AU - Haljasmägi, Liis
AU - Migaud, Mélanie
AU - Särekannu, Karita
AU - Maslovskaja, Julia
AU - de Prost, Nicolas
AU - Tandjaoui-Lambiotte, Yacine
AU - Luyt, Charles-Edouard
AU - Amador-Borrero, Blanca
AU - Gaudet, Alexandre
AU - Poissy, Julien
AU - Morel, Pascal
AU - Richard, Pascale
AU - Cognasse, Fabrice
AU - Troya, Jesus
AU - Trouillet-Assant, Sophie
AU - Belot, Alexandre
AU - Saker, Kahina
AU - Garçon, Pierre
AU - Rivière, Jacques G
AU - Lagier, Jean-Christophe
AU - Gentile, Stéphanie
AU - Rosen, Lindsey
AU - Shaw, Elana
AU - Morio, Tomohiro
AU - Tanaka, Junko
AU - Dalmau, David
AU - Tharaux, Pierre-Louis
AU - Sene, Damien
AU - Stepanian, Alain
AU - Mégarbane, Bruno
AU - Triantafyllia, Vasiliki
AU - Fekkar, Arnaud
AU - Heath, James
AU - Franco, Jose
AU - Anaya, Juan-Manuel
AU - Solé-Violán, Jordi
AU - Imberti, Luisa
AU - Biondi, Andrea
AU - Bonfanti, Paolo
AU - Castagnoli, Riccardo
AU - Delmonte, Ottavia
AU - Zhang, Yu
AU - Snow, Andrew
AU - Holland, Steve
AU - Biggs, Catherine
AU - Moncada-Vélez, Marcela
AU - Arias, Andrés
AU - Lorenzo, Lazaro
AU - Boucherit, Soraya
AU - Anglicheau, Dany
AU - Planas, Anna
AU - Haerynck, Filomeen
AU - Duvlis, Sotirija
AU - Nussbaum, Robert
AU - Ozcelik, Tayfun
AU - Keles, Sevgi
AU - Bousfiha, Aziz
AU - Bakkouri, Jalila El
AU - Ramirez-Santana, Carolina
AU - Paul, Stéphane
AU - Pan-Hammarstrom, Qiang
AU - Hammarstrom, Lennart
AU - Dupont, Annabelle
AU - Kurolap, Alina
AU - Metz, Christine
AU - Aiuti, Alessandro
AU - Casari, Giorgio
AU - Lampasona, Vito
AU - Ciceri, Fabio
AU - Barreiros, Lucila
AU - Dominguez-Garrido, Elena
AU - Vidigal, Mateus
AU - Zatz, Mayana
AU - van de Beek, Diederik
AU - Sahanic, Sabina
AU - Tancevski, Ivan
AU - Stepanovskyy, Yurii
AU - Boyarchuk, Oksana
AU - Nukui, Yoko
AU - Tsumura, Miyuki
AU - Vidaur, Loreto
AU - Tangye, Stuart
AU - Burrel, Sonia
AU - Duffy, Darragh
AU - Quintana-Murci, Lluis
AU - Klocperk, Adam
AU - Kann, Nelli
AU - Shcherbina, Anna
AU - Lau, Yu-Lung
AU - Leung, Daniel
AU - Coulongeat, Matthieu
AU - Marlet, Julien
AU - Koning, Rutger
AU - Reyes, Luis
AU - Chauvineau-Grenier, Angélique
AU - Venet, Fabienne
AU - Monneret, Guillaume
AU - Nussenzweig, Michel
AU - Arrestier, Romain
AU - Boudhabhay, Idris
AU - Baris-Feldman, Hagit
AU - Hagin, David
AU - Wauters, Joost
AU - Meyts, Isabelle
AU - Dyer, Adam
AU - Kennelly, Sean
AU - Bourke, Nollaig
AU - Halwani, Rabih
AU - Sharif-Askari, Fatemeh
AU - Dorgham, Karim
AU - Sallette, Jérôme
AU - Mehlal-Sedkaoui, Souad
AU - AlKhater, Suzan
AU - Rigo-Bonnin, Raúl
AU - Morandeira, Francisco
AU - Roussel, Lucie
AU - Vinh, Donald
AU - Erikstrup, Christian
AU - Condino-Neto, Antonio
AU - Prando, Carolina
AU - Bondarenko, Anastasiia
AU - Spaan, András
AU - Gilardin, Laurent
AU - Fellay, Jacques
AU - Lyonnet, Stanislas
AU - Bilguvar, Kaya
AU - Lifton, Richard
AU - Mane, Shrikant
AU - Anderson, Mark
AU - Boisson, Bertrand
AU - Béziat, Vivien
AU - Zhang, Shen-Ying
AU - Andreakos, Evangelos
AU - Hermine, Olivier
AU - Pujol, Aurora
AU - Peterson, Pärt
AU - Mogensen, Trine Hyrup
AU - Rowen, Lee
AU - Mond, James
AU - Debette, Stéphanie
AU - deLamballerie, Xavier
AU - Burdet, Charles
AU - Bouadma, Lila
AU - Zins, Marie
AU - Soler-Palacin, Pere
AU - Colobran, Roger
AU - Gorochov, Guy
AU - Solanich, Xavier
AU - Susen, Sophie
AU - Martinez-Picado, Javier
AU - Raoult, Didier
AU - Vasse, Marc
AU - Gregersen, Peter
AU - Rodríguez-Gallego, Carlos
AU - Piemonti, Lorenzo
AU - Notarangelo, Luigi
AU - Su, Helen
AU - Kisand, Kai
AU - Okada, Satoshi
AU - Puel, Anne
AU - Jouanguy, Emmanuelle
AU - Rice, Charles
AU - Tiberghien, Pierre
AU - Zhang, Qian
AU - Casanova, Jean-Laurent
AU - Abel, Laurent
AU - Cobat, Aurélie
PY - 2022/1/14
Y1 - 2022/1/14
N2 - SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.
AB - SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.
U2 - https://doi.org/10.21203/rs.3.rs-1225906/v1
DO - https://doi.org/10.21203/rs.3.rs-1225906/v1
M3 - Article
C2 - 35043109
JO - Research square
JF - Research square
ER -