Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

Bastard, P.; Gervais, A.; Taniguchi, M.; Saare, L.; Sarekannu, K.; Le Voyer, T.; Philippot, Q.; Rosain, J.; Bizien, L.; Asano, T.; Garcia-Prat, M.; Parra-Martinez, A.; Migaud, M.; Tsumura, M.; Conti, F.; Belot, A.; Riviere, J. G.; Morio, T.; Tanaka, J.; Javouhey, E.; Haerynck, F.; Duvlis, S.; Ozcelik, T.; Keles, S.; Tandjaoui-Lambiotte, Y.; Escoda, S.; Husain, M.; Pan-Hammarstrom, Q.; Hammarstrom, L.; Ahlijah, G.; Abi Haidar, A.; Soudee, C.; Arseguel, V.; Abolhassani, H.; Sahanic, S.; Tancevski, I.; Nukui, Y.; Hayakawa, S.; Chrousos, G. P.; Michos, A.; Tatsi, E. -B.; Filippatos, F.; Rodriguez-Palmero, A.; Troya, J.; Tipu, I.; Meyts, I.; Roussel, L.; Ostrowski, S. R.; Schidlowski, L.; Prando, C.; Condino-Neto, A.; Cheikh, N.; Bousfiha, A. A.; El Bakkouri, J.; Peterson, P.; Pujol, A.; Levy, R.; Quartier, P.; Vinh, D. C.; Boisson, B.; Beziat, V.; Zhang, S. -Y.; Borghesi, A.; Pession, A.; Andreakos, E.; Marr, N.; Mentis, A. -F. A.; Mogensen, T. H.; Rodriguez-Gallego, C.; Soler-Palacin, P.; Colobran, R.; Tillmann, V.; Neven, B.; Trouillet-Assant, S.; Brodin, P.; Abel, L.; Jouanguy, E.; Zhang, Q.; Martinon-Torres, F.; Salas, A.; Gomez-Carballa, A.; Gonzalez-Granado, L. I.; Kisand, K.; Okada, S.; Puel, A.; Cobat, A.; Casanova, J. -L.

doi:10.1084/jem.20231353

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.

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children / Bastard P.; Gervais A.; Taniguchi M.; Saare L.; Sarekannu K.; Le Voyer T.; Philippot Q.; Rosain J.; Bizien L.; Asano T.; Garcia-Prat M.; Parra-Martinez A.; Migaud M.; Tsumura M.; Conti F.; Belot A.; Riviere J.G.; Morio T.; Tanaka J.; Javouhey E.; Haerynck F.; Duvlis S.; Ozcelik T.; Keles S.; Tandjaoui-Lambiotte Y.; Escoda S.; Husain M.; Pan-Hammarstrom Q.; Hammarstrom L.; Ahlijah G.; Abi Haidar A.; Soudee C.; Arseguel V.; Abolhassani H.; Sahanic S.; Tancevski I.; Nukui Y.; Hayakawa S.; Chrousos G.P.; Michos A.; Tatsi E.-B.; Filippatos F.; Rodriguez-Palmero A.; Troya J.; Tipu I.; Meyts I.; Roussel L.; Ostrowski S.R.; Schidlowski L.; Prando C.; Condino-Neto A.; Cheikh N.; Bousfiha A.A.; El Bakkouri J.; Peterson P.; Pujol A.; Levy R.; Quartier P.; Vinh D.C.; Boisson B.; Beziat V.; Zhang S.-Y.; Borghesi A.; Pession A.; Andreakos E.; Marr N.; Mentis A.-F.A.; Mogensen T.H.; Rodriguez-Gallego C.; Soler-Palacin P.; Colobran R.; Tillmann V.; Neven B.; Trouillet-Assant S.; Brodin P.; Abel L.; Jouanguy E.; Zhang Q.; Martinon-Torres F.; Salas A.; Gomez-Carballa A.; Gonzalez-Granado L.I.; Kisand K.; Okada S.; Puel A.; Cobat A.; Casanova J.-L.. - In: THE JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 1540-9538. - ELETTRONICO. - 221:2(2024), pp. e20231353.1-e20231353.45. [10.1084/jem.20231353]