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: SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y 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, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies
Manry, Jérémy;Bastard, Paul;Gervais, Adrian;Le Voyer, Tom;Rosain, Jérémie;Philippot, Quentin;Michailidis, Eleftherios;Hoffmann, Hans-Heinrich;Eto, Shohei;Garcia-Prat, Marina;Bizien, Lucy;Parra-Martínez, Alba;Yang, Rui;Haljasmägi, Liis;Migaud, Mélanie;Särekannu, Karita;Maslovskaja, Julia;de Prost, Nicolas;Tandjaoui-Lambiotte, Yacine;Luyt, Charles-Edouard;Amador-Borrero, Blanca;Gaudet, Alexandre;Poissy, Julien;Morel, Pascal;Richard, Pascale;Cognasse, Fabrice;Troya, Jesús;Trouillet-Assant, Sophie;Belot, Alexandre;Saker, Kahina;Garçon, Pierre;Rivière, Jacques G;Lagier, Jean-Christophe;Gentile, Stéphanie;Rosen, Lindsey B;Shaw, Elana;Morio, Tomohiro;Tanaka, Junko;Dalmau, David;Tharaux, Pierre-Louis;Sene, Damien;Stepanian, Alain;Mégarbane, Bruno;Triantafyllia, Vasiliki;Fekkar, Arnaud;Heath, James R;Franco, José Luis;Anaya, Juan-Manuel;Solé-Violán, Jordi;Imberti, Luisa;Biondi, Andrea;Bonfanti, Paolo;Castagnoli, Riccardo;Delmonte, Ottavia M;Zhang, Yu;Snow, Andrew L;Holland, Steven M;Biggs, Catherine M;Moncada-Vélez, Marcela;Arias, Andrés Augusto;Lorenzo, Lazaro;Boucherit, Soraya;Anglicheau, Dany;Planas, Anna M;Haerynck, Filomeen;Duvlis, Sotirija;Ozcelik, Tayfun;Keles, Sevgi;Bousfiha, Ahmed A;El Bakkouri, Jalila;Ramirez-Santana, Carolina;Paul, Stéphane;Pan-Hammarström, Qiang;Hammarström, Lennart;Dupont, Annabelle;Kurolap, Alina;Metz, Christine N;Aiuti, Alessandro;Casari, Giorgio;Lampasona, Vito;Ciceri, Fabio;Barreiros, Lucila A;Dominguez-Garrido, Elena;Vidigal, Mateus;Zatz, Mayana;van de Beek, Diederik;Sahanic, Sabina;Tancevski, Ivan;Stepanovskyy, Yurii;Boyarchuk, Oksana;Nukui, Yoko;Tsumura, Miyuki;Vidaur, Loreto;Tangye, Stuart G;Burrel, Sonia;Duffy, Darragh;Quintana-Murci, Lluis;Klocperk, Adam;Kann, Nelli Y;Shcherbina, Anna;Lau, Yu-Lung;Leung, Daniel;Coulongeat, Matthieu;Marlet, Julien;Koning, Rutger;Reyes, Luis Felipe;Chauvineau-Grenier, Angélique;Venet, Fabienne;Monneret, Guillaume;Nussenzweig, Michel C;Arrestier, Romain;Boudhabhay, Idris;Baris-Feldman, Hagit;Hagin, David;Wauters, Joost;Meyts, Isabelle;Dyer, Adam H;Kennelly, Sean P;Bourke, Nollaig M;Halwani, Rabih;Sharif-Askari, Fatemeh Saheb;Dorgham, Karim;Sallette, Jérôme;Sedkaoui, Souad Mehlal;AlKhater, Suzan;Rigo-Bonnin, Raúl;Morandeira, Francisco;Roussel, Lucie;Vinh, Donald C;Erikstrup, Christian;Condino-Neto, Antonio;Prando, Carolina;Bondarenko, Anastasiia;Spaan, András N;Gilardin, Laurent;Fellay, Jacques;Lyonnet, Stanislas;Bilguvar, Kaya;Lifton, Richard P;Mane, Shrikant;Anderson, Mark S;Boisson, Bertrand;Béziat, Vivien;Zhang, Shen-Ying;Andreakos, Evangelos;Hermine, Olivier;Pujol, Aurora;Peterson, Pärt;Mogensen, Trine H;Rowen, Lee;Mond, James;Debette, Stéphanie;de Lamballerie, Xavier;Burdet, Charles;Bouadma, Lila;Zins, Marie;Soler-Palacin, Pere;Colobran, Roger;Gorochov, Guy;Solanich, Xavier;Susen, Sophie;Martinez-Picado, Javier;Raoult, Didier;Vasse, Marc;Gregersen, Peter K;Piemonti, Lorenzo;Rodríguez-Gallego, Carlos;Notarangelo, Luigi D;Su, Helen C;Kisand, Kai;Okada, Satoshi;Puel, Anne;Jouanguy, Emmanuelle;Rice, Charles M;Tiberghien, Pierre;Zhang, Qian;Casanova, Jean-Laurent;Abel, Laurent;Cobat, Aurélie
2022-01-01
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y 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, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
: SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population.
COVID-19 autoantibodies infection fatality rate relative risk type I IFNs
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/129015
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.