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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-alpha, IFN-omega, and/or IFN-beta are found in similar to 20% of deceased patients across age groups, and in similar to 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-alpha 2 or IFN-omega, 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-alpha 2 or IFN-omega, 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-alpha 2 and IFN-omega. 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.
Keywords
Multidisciplinary, COVID-19, type I IFNs, autoantibodies, relative risk, infection fatality rate, CHRONIC MUCOCUTANEOUS CANDIDIASIS, DISEASE, INFECTION, IMMUNITY

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MLA
Manry, Jérémy, et al. “The Risk of COVID-19 Death Is Much Greater and Age Dependent with Type I IFN Autoantibodies.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 119, no. 21, 2022, doi:10.1073/pnas.2200413119.
APA
Manry, J., Bastard, P., Gervais, A., Le Voyer, T., Rosain, J., Philippot, Q., … Etablissement Français du Sang Study group, [missing]. (2022). The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119(21). https://doi.org/10.1073/pnas.2200413119
Chicago author-date
Manry, Jérémy, Paul Bastard, Adrian Gervais, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Eleftherios Michailidis, et al. 2022. “The Risk of COVID-19 Death Is Much Greater and Age Dependent with Type I IFN Autoantibodies.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119 (21). https://doi.org/10.1073/pnas.2200413119.
Chicago author-date (all authors)
Manry, Jérémy, Paul Bastard, Adrian Gervais, Tom Le Voyer, Jérémie Rosain, Quentin Philippot, Eleftherios Michailidis, Hans-Heinrich Hoffmann, Shohei Eto, Marina Garcia-Prat, Lucy Bizien, Alba Parra-Martínez, Rui Yang, Liis Haljasmägi, Mélanie Migaud, Karita Särekannu, Julia Maslovskaja, Nicolas de Prost, Yacine Tandjaoui-Lambiotte, Charles-Edouard Luyt, Blanca Amador-Borrero, Alexandre Gaudet, Julien Poissy, Pascal Morel, Pascale Richard, Fabrice Cognasse, Jesús Troya, Sophie Trouillet-Assant, Alexandre Belot, Kahina Saker, Pierre Garçon, Jacques G. Rivière, Jean-Christophe Lagier, Stéphanie Gentile, Lindsey B. Rosen, Elana Shaw, Tomohiro Morio, Junko Tanaka, David Dalmau, Pierre-Louis Tharaux, Damien Sene, Alain Stepanian, Bruno Mégarbane, Vasiliki Triantafyllia, Arnaud Fekkar, James R. Heath, José Luis Franco, Juan-Manuel Anaya, Jordi Solé-Violán, Luisa Imberti, Andrea Biondi, Paolo Bonfanti, Riccardo Castagnoli, Ottavia M. Delmonte, Yu Zhang, Andrew L. Snow, Steven M. Holland, Catherine M. Biggs, Marcela Moncada-Vélez, Andrés Augusto Arias, Lazaro Lorenzo, Soraya Boucherit, Dany Anglicheau, Anna M. Planas, Filomeen Haerynck, Sotirija Duvlis, Tayfun Ozcelik, Sevgi Keles, Ahmed A. Bousfiha, Jalila El Bakkouri, Carolina Ramirez-Santana, Stéphane Paul, Qiang Pan-Hammarström, Lennart Hammarström, Annabelle Dupont, Alina Kurolap, Christine N. Metz, Alessandro Aiuti, Giorgio Casari, Vito Lampasona, Fabio Ciceri, Lucila A. Barreiros, Elena Dominguez-Garrido, Mateus Vidigal, Mayana Zatz, Diederik van de Beek, Sabina Sahanic, Ivan Tancevski, Yurii Stepanovskyy, Oksana Boyarchuk, Yoko Nukui, Miyuki Tsumura, Loreto Vidaur, Stuart G. Tangye, Sonia Burrel, Darragh Duffy, Lluis Quintana-Murci, Adam Klocperk, Nelli Y. Kann, Anna Shcherbina, Yu-Lung Lau, Daniel Leung, Matthieu Coulongeat, Julien Marlet, Rutger Koning, Luis Felipe Reyes, Angélique Chauvineau-Grenier, Fabienne Venet, Guillaume Monneret, Michel C. Nussenzweig, Romain Arrestier, Idris Boudhabhay, Hagit Baris-Feldman, David Hagin, Joost Wauters, Isabelle Meyts, Adam H. Dyer, Sean P. Kennelly, Nollaig M. Bourke, Rabih Halwani, Fatemeh Saheb Sharif-Askari, Karim Dorgham, Jérôme Sallette, Souad Mehlal Sedkaoui, Suzan AlKhater, Raúl Rigo-Bonnin, Francisco Morandeira, Lucie Roussel, Donald C. Vinh, Christian Erikstrup, Antonio Condino-Neto, Carolina Prando, Anastasiia Bondarenko, András N. Spaan, Laurent Gilardin, Jacques Fellay, Stanislas Lyonnet, Kaya Bilguvar, Richard P. Lifton, Shrikant Mane, Mark S. Anderson, Bertrand Boisson, Vivien Béziat, Shen-Ying Zhang, Evangelos Andreakos, Olivier Hermine, Aurora Pujol, Pärt Peterson, Trine H. Mogensen, Lee Rowen, James Mond, Stéphanie Debette, Xavier de Lamballerie, Charles Burdet, Lila Bouadma, Marie Zins, Pere Soler-Palacin, Roger Colobran, Guy Gorochov, Xavier Solanich, Sophie Susen, Javier Martinez-Picado, Didier Raoult, Marc Vasse, Peter K. Gregersen, Lorenzo Piemonti, Carlos Rodríguez-Gallego, Luigi D. Notarangelo, Helen C. Su, Kai Kisand, Satoshi Okada, Anne Puel, Emmanuelle Jouanguy, Charles M. Rice, Pierre Tiberghien, Qian Zhang, Jean-Laurent Casanova, Laurent Abel, Aurélie Cobat, [missing] HGID Lab, [missing] COVID Clinicians, [missing] COVID-STORM Clinicians, [missing] NIAID Immune Response to COVID Group, [missing] NH-COVAIR Study Group, [missing] Danish CHGE, [missing] Danish Blood Donor Study, [missing] St. James’s Hospital, SARS CoV2 Interest Group, [missing] French COVID Cohort Study Group, [missing] Imagine COVID-Group, [missing] The Milieu Intérieur Consortium, [missing] CoV-Contact Cohort, [missing] Amsterdam UMC Covid-19 Biobank Investigators, [missing] COVID Human Genetic Effort, [missing] CP-COVID-19 Group, [missing] CONSTANCES cohort, [missing] 3C-Dijon Study, [missing] Cerba Health-Care, and [missing] Etablissement Français du Sang Study group. 2022. “The Risk of COVID-19 Death Is Much Greater and Age Dependent with Type I IFN Autoantibodies.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119 (21). doi:10.1073/pnas.2200413119.
Vancouver
1.
Manry J, Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, et al. The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2022;119(21).
IEEE
[1]
J. Manry et al., “The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies,” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 119, no. 21, 2022.
@article{8767983,
  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-alpha, IFN-omega, and/or IFN-beta are found in similar to 20% of deceased patients across age groups, and in similar to 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-alpha 2 or IFN-omega, 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-alpha 2 or IFN-omega, 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-alpha 2 and IFN-omega. 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.}},
  articleno    = {{e2200413119}},
  author       = {{Manry, Jérémy and Bastard, Paul and Gervais, Adrian and Le Voyer, Tom and Rosain, Jérémie and Philippot, Quentin and Michailidis, Eleftherios and Hoffmann, Hans-Heinrich and Eto, Shohei and Garcia-Prat, Marina and Bizien, Lucy and Parra-Martínez, Alba and Yang, Rui and Haljasmägi, Liis and Migaud, Mélanie and Särekannu, Karita and Maslovskaja, Julia and de Prost, Nicolas and Tandjaoui-Lambiotte, Yacine and Luyt, Charles-Edouard and Amador-Borrero, Blanca and Gaudet, Alexandre and Poissy, Julien and Morel, Pascal and Richard, Pascale and Cognasse, Fabrice and Troya, Jesús and Trouillet-Assant, Sophie and Belot, Alexandre and Saker, Kahina and Garçon, Pierre and Rivière, Jacques G. and Lagier, Jean-Christophe and Gentile, Stéphanie and Rosen, Lindsey B. and Shaw, Elana and Morio, Tomohiro and Tanaka, Junko and Dalmau, David and Tharaux, Pierre-Louis and Sene, Damien and Stepanian, Alain and Mégarbane, Bruno and Triantafyllia, Vasiliki and Fekkar, Arnaud and Heath, James R. and Franco, José Luis and Anaya, Juan-Manuel and Solé-Violán, Jordi and Imberti, Luisa and Biondi, Andrea and Bonfanti, Paolo and Castagnoli, Riccardo and Delmonte, Ottavia M. and Zhang, Yu and Snow, Andrew L. and Holland, Steven M. and Biggs, Catherine M. and Moncada-Vélez, Marcela and Arias, Andrés Augusto and Lorenzo, Lazaro and Boucherit, Soraya and Anglicheau, Dany and Planas, Anna M. and Haerynck, Filomeen and Duvlis, Sotirija and Ozcelik, Tayfun and Keles, Sevgi and Bousfiha, Ahmed A. and El Bakkouri, Jalila and Ramirez-Santana, Carolina and Paul, Stéphane and Pan-Hammarström, Qiang and Hammarström, Lennart and Dupont, Annabelle and Kurolap, Alina and Metz, Christine N. and Aiuti, Alessandro and Casari, Giorgio and Lampasona, Vito and Ciceri, Fabio and Barreiros, Lucila A. and Dominguez-Garrido, Elena and Vidigal, Mateus and Zatz, Mayana and van de Beek, Diederik and Sahanic, Sabina and Tancevski, Ivan and Stepanovskyy, Yurii and Boyarchuk, Oksana and Nukui, Yoko and Tsumura, Miyuki and Vidaur, Loreto and Tangye, Stuart G. and Burrel, Sonia and Duffy, Darragh and Quintana-Murci, Lluis and Klocperk, Adam and Kann, Nelli Y. and Shcherbina, Anna and Lau, Yu-Lung and Leung, Daniel and Coulongeat, Matthieu and Marlet, Julien and Koning, Rutger and Reyes, Luis Felipe and Chauvineau-Grenier, Angélique and Venet, Fabienne and Monneret, Guillaume and Nussenzweig, Michel C. and Arrestier, Romain and Boudhabhay, Idris and Baris-Feldman, Hagit and Hagin, David and Wauters, Joost and Meyts, Isabelle and Dyer, Adam H. and Kennelly, Sean P. and Bourke, Nollaig M. and Halwani, Rabih and Sharif-Askari, Fatemeh Saheb and Dorgham, Karim and Sallette, Jérôme and Sedkaoui, Souad Mehlal and AlKhater, Suzan and Rigo-Bonnin, Raúl and Morandeira, Francisco and Roussel, Lucie and Vinh, Donald C. and Erikstrup, Christian and Condino-Neto, Antonio and Prando, Carolina and Bondarenko, Anastasiia and Spaan, András N. and Gilardin, Laurent and Fellay, Jacques and Lyonnet, Stanislas and Bilguvar, Kaya and Lifton, Richard P. and Mane, Shrikant and Anderson, Mark S. and Boisson, Bertrand and Béziat, Vivien and Zhang, Shen-Ying and Andreakos, Evangelos and Hermine, Olivier and Pujol, Aurora and Peterson, Pärt and Mogensen, Trine H. and Rowen, Lee and Mond, James and Debette, Stéphanie and de Lamballerie, Xavier and Burdet, Charles and Bouadma, Lila and Zins, Marie and Soler-Palacin, Pere and Colobran, Roger and Gorochov, Guy and Solanich, Xavier and Susen, Sophie and Martinez-Picado, Javier and Raoult, Didier and Vasse, Marc and Gregersen, Peter K. and Piemonti, Lorenzo and Rodríguez-Gallego, Carlos and Notarangelo, Luigi D. and Su, Helen C. and Kisand, Kai and Okada, Satoshi and Puel, Anne and Jouanguy, Emmanuelle and Rice, Charles M. and Tiberghien, Pierre and Zhang, Qian and Casanova, Jean-Laurent and Abel, Laurent and Cobat, Aurélie and HGID Lab, [missing] and COVID Clinicians, [missing] and COVID-STORM Clinicians, [missing] and NIAID Immune Response to COVID Group, [missing] and NH-COVAIR Study Group, [missing] and Danish CHGE, [missing] and Danish Blood Donor Study, [missing] and St. James's Hospital, SARS CoV2 Interest Group, [missing] and French COVID Cohort Study Group, [missing] and Imagine COVID-Group, [missing] and The Milieu Intérieur Consortium, [missing] and CoV-Contact Cohort, [missing] and Amsterdam UMC Covid-19 Biobank Investigators, [missing] and COVID Human Genetic Effort, [missing] and CP-COVID-19 Group, [missing] and CONSTANCES cohort, [missing] and 3C-Dijon Study, [missing] and Cerba Health-Care, [missing] and Etablissement Français du Sang Study group, [missing]}},
  issn         = {{0027-8424}},
  journal      = {{PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}},
  keywords     = {{Multidisciplinary,COVID-19,type I IFNs,autoantibodies,relative risk,infection fatality rate,CHRONIC MUCOCUTANEOUS CANDIDIASIS,DISEASE,INFECTION,IMMUNITY}},
  language     = {{eng}},
  number       = {{21}},
  pages        = {{10}},
  title        = {{The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies}},
  url          = {{http://doi.org/10.1073/pnas.2200413119}},
  volume       = {{119}},
  year         = {{2022}},
}

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