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 - Dalgard, Clifton L.
N1 - Publisher Copyright:
© 2024, Rockefeller University Press. All rights reserved.
PY - 2024
Y1 - 2024
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 -