Abstract
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7–9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2–5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6–35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1–9.6]) of IFN-ω and/or IFN-α2.
Original language | English |
---|---|
Article number | e20231353 |
Journal | Journal of Experimental Medicine |
Volume | 221 |
Issue number | 2 |
DOIs | |
State | Published - Jan 1 2024 |
Keywords
- COVID-19
- Immunodeficiency
- Infectious disease and host defense
- Innate immunity and inflammation
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In: Journal of Experimental Medicine, Vol. 221, No. 2, e20231353, 01.01.2024.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children
AU - COVID Clinicians
AU - GEN-COVID Study Group
AU - COVID Human Genetic Effort
AU - Bastard, Paul
AU - Gervais, Adrian
AU - Taniguchi, Maki
AU - Saare, Liisa
AU - Särekannu, Karita
AU - Voyer, Tom Le
AU - Philippot, Quentin
AU - Rosain, Jérémie
AU - Bizien, Lucy
AU - Asano, Takaki
AU - Garcia-Prat, Marina
AU - Parra-Martínez, Alba
AU - Migaud, Mélanie
AU - Tsumura, Miyuki
AU - Conti, Francesca
AU - Belot, Alexandre
AU - Rivière, Jacques G.
AU - Morio, Tomohiro
AU - Tanaka, Junko
AU - Javouhey, Etienne
AU - Haerynck, Filomeen
AU - Duvlis, Sotirija
AU - Ozcelik, Tayfun
AU - Keles, Sevgi
AU - Tandjaoui-Lambiotte, Yacine
AU - Escoda, Simon
AU - Husain, Maya
AU - Pan-Hammarström, Qiang
AU - Hammarström, Lennart
AU - Ahlijah, Gloria
AU - Haidar, Anthony Abi
AU - Soudee, Camille
AU - Arseguel, Vincent
AU - Abolhassani, Hassan
AU - Sahanic, Sabina
AU - Tancevski, Ivan
AU - Nukui, Yoko
AU - Hayakawa, Seiichi
AU - Chrousos, George P.
AU - Michos, Athanasios
AU - Tatsi, Elizabeth Barbara
AU - Filippatos, Filippos
AU - Rodriguez-Palmero, Agusti
AU - Troya, Jesus
AU - Tipu, Imran
AU - Meyts, Isabelle
AU - Roussel, Lucie
AU - Ostrowski, Sisse Rye
AU - Schidlowski, Laire
AU - Prando, Carolina
AU - Condino-Neto, Antonio
AU - Cheikh, Nathalie
AU - Bousfiha, Ahmed A.
AU - Bakkouri, Jalila El
AU - Peterson, Pärt
AU - Pujol, Aurora
AU - Lévy, Romain
AU - Quartier, Pierre
AU - Vinh, Donald C.
AU - Boisson, Bertrand
AU - Béziat, Vivien
AU - Zhang, Shen Ying
AU - Borghesi, Alessandro
AU - Pession, Andrea
AU - Andreakos, Evangelos
AU - Marr, Nico
AU - Mentis, Alexios Fotios A.
AU - H.mogensen, Trine
AU - Rodríguez-Gallego, Carlos
AU - Soler-Palacin, Pere
AU - Colobran, Roger
AU - Tillmann, Vallo
AU - Neven, Bénédicte
AU - Trouillet-Assant, Sophie
AU - Brodin, Petter
AU - Abel, Laurent
AU - Jouanguy, Emmanuelle
AU - Zhang, Qian
AU - Martinón-Torres, Federico
AU - Salas, Antonio
AU - Gómez-Carballa, Alberto
AU - Gonzalez-Granado, Luis I.
AU - Kisand, Kai
AU - Okada, Satoshi
AU - Puel, Anne
AU - Cobat, Aurélie
AU - Casanova, Jean Laurent
AU - Aguilera-Albesa, Sergio
AU - Alkhater, Suzan A.
AU - Alkan, Gulsum
AU - Castagnoli, Riccardo
AU - Cyrus, Cyril
AU - Bozdemir, Sefika Elmas
AU - Emiroglu, Melike
AU - Gulhan, Belgin
AU - Erdeniz, Emine Hafize
AU - Hatipoglu, Nevin
AU - Bayhan, Gülsün Iclal
AU - Jabandziev, Petr
AU - Yuksek, Saliha Kanik
AU - Karbuz, Adem
AU - Öz, Şadiye Kübra Tüter
AU - Marseglia, Gian Luigi
AU - Akcan, Ozge Metin
AU - Kılıç, Ahmet Osman
AU - Parlakay, Aslinur Ozkaya
AU - Papadaki, Maria
AU - Slaba, Katerina
AU - Sevketoglu, Esra
AU - Valencia-Ramos, Juan
AU - Yahşi, Aysun
AU - Tuala, Currás
AU - Urbieta, Ana Isabel Dacosta
AU - Esteban, Blanca Díaz
AU - Santalla, María Jesús Domínguez
AU - Pérez, Cristina Fernández
AU - Villaverde, Juan Fernández
AU - Rodríguez, Cristóbal Galbán
AU - Allut, José Luis García
AU - Vicente, Luisa García
AU - Vázquez, Elena Giráldez
AU - Carballa, Alberto Gómez
AU - Rial, José Gómez
AU - Barcala, Francisco Javier González
AU - Liñares, Beatriz Guerra
AU - Iglesias, Pilar Leboráns
AU - Massa, Beatriz Lence
AU - Fuentes, Marta Lendoiro
AU - Franco, Montserrat López
AU - Lago, Ana López
AU - Cruz, Daniel Navarro De la
AU - Masid, Eloína Núñez
AU - Devesa, Juan Bautista Ortolá
AU - Seco, Jacobo Pardo
AU - Núñez, María Pazo
AU - Bernal, Marisa Pérez Del Molino
AU - Freixo, Hugo Pérez
AU - Rodríguez, Lidia Piñeiro
AU - Pischedda, Sara
AU - Romero, Manuel Portela
AU - Reino, Antonio Pose
AU - Hervella, Gloria María Prada
AU - Verdes, Teresa Queiro
AU - Collazo, Lorenzo Redondo
AU - Casuso, Patricia Regueiro
AU - García, Susana Rey
AU - Vázquez, Sara Rey
AU - Blanco, Vanessa Riveiro
AU - Calle, Irene Rivero
AU - Velasco, Carmen Rivero
AU - Núñez, Nuria Rodríguez
AU - Sánchez, Carmen Rodríguez Tenreiro
AU - Paz, Eva Saborido
AU - Orayyou, José Miguel Sadiki
AU - Villanueva, Carla Saito
AU - Fernández, Sonia Serén
AU - Sanmartín, Pablo Souto
AU - Muñiz, Manuel Taboada
AU - Pena, Rocío Trastoy
AU - Castellano, Mercedes Treviño
AU - Cuadrado, Luis Valdés
AU - García, Pablo Varela
AU - Iglesias, María Soledad Vilas
AU - Lasheras, Sandra Viz
AU - Ferreiro-Iglesias, Rocio
AU - Bastón-Rey, Iria
AU - Calviño-Suárez, Cristina
AU - Aiuti, Alessandro
AU - Al-Muhsen, Saleh
AU - Al-Mulla, Fahd
AU - Amara, Ali
AU - Anderson, Mark S.
AU - Arias, Andrés A.
AU - Arkin, Lisa M.
AU - Feldman, Hagit Baris
AU - Biggs, Catherine M.
AU - Bogunovic, Dusan
AU - Bolze, Alexandre
AU - Bondarenko, Anastasiia
AU - Bryceson, Yenan
AU - Butte, Manish J.
AU - Casari, Giorgio
AU - Christodoulou, John
AU - Constantinescu, Stefan N.
AU - Cooper, Megan A.
AU - Dalgard, Clifton L.
AU - Desai, Murkesh
AU - Drolet, Beth A.
AU - Duval, Xavier
AU - Baghdadi, Jamila El
AU - Eloy, Philippine
AU - Espinosa-Padilla, Sara
AU - Fellay, Jacques
AU - Flores, Carlos
AU - Franco, José Luis
AU - Froidure, Antoine
AU - Gorochov, Guy
AU - Gregersen, Peter K.
AU - Grimbacher, Bodo
AU - Hagin, David
N1 - Publisher Copyright: © 2024, Rockefeller University Press. All rights reserved.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7–9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2–5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6–35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1–9.6]) of IFN-ω and/or IFN-α2.
AB - We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7–9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2–5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6–35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1–9.6]) of IFN-ω and/or IFN-α2.
KW - COVID-19
KW - Immunodeficiency
KW - Infectious disease and host defense
KW - Innate immunity and inflammation
UR - http://www.scopus.com/inward/record.url?scp=85181628485&partnerID=8YFLogxK
U2 - 10.1084/jem.20231353
DO - 10.1084/jem.20231353
M3 - Article
C2 - 38175961
AN - SCOPUS:85181628485
SN - 0022-1007
VL - 221
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 2
M1 - e20231353
ER -