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.; Särekannu, K.; Voyer, T. L.; Philippot, Q.; Rosain, J.; Bizien, L.; Asano, T.; Garcia-Prat, M.; Parra-Martínez, A.; Migaud, M.; Tsumura, M.; Conti, F.; Belot, A.; Rivière, J. G.; Morio, T.; Tanaka, J.; Javouhey, E.; Haerynck, F.; Duvlis, S.; Ozcelik, T.; Keles, S.; Tandjaoui-Lambiotte, Y.; Escoda, S.; Husain, M.; Pan-Hammarström, Q.; Hammarström, L.; Ahlijah, G.; Haidar, A. 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.; Bakkouri, J. E.; Peterson, P.; Pujol, A.; Lévy, R.; Quartier, P.; Vinh, D. C.; Boisson, B.; Béziat, V.; Zhang, S. Y.; Borghesi, A.; Pession, A.; Andreakos, E.; Marr, N.; Mentis, A. F. A.; H. Mogensen T.,; Rodríguez-Gallego, C.; Soler-Palacin, P.; Colobran, R.; Tillmann, V.; Neven, B.; Trouillet-Assant, S.; Brodin, P.; Abel, L.; Jouanguy, E.; Zhang, Q.; Martinón-Torres, F.; Salas, A.; Gómez-Carballa, A.; Gonzalez-Granado, L. I.; Kisand, K.; Okada, S.; Puel, A.; Cobat, A.; Casanova, J. L.; Casari, G.; Aguilera-Albesa, S.; Alkhater, S. A.; Alkan, G.; Castagnoli, R.; Cyrus, C.; Bozdemir, S. E.; Emiroglu, M.; Gulhan, B.; Erdeniz, E. H.; Hatipoglu, N.; Bayhan, G. I.; Jabandziev, P.; Yuksek, S. K.

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.

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega 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-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. 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-omega and/or IFN-alpha 2.

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., Särekannu, K., Voyer, T.L., Philippot, Q., Rosain, J., Bizien, L., Asano, T., Garcia-Prat, M., Parra-Martínez, A., Migaud, M., Tsumura, M., Conti, F., Belot, A., Rivière, J.G., Morio, T., Tanaka, J., Javouhey, E., et al.. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - 221:2(2024). [10.1084/jem.20231353]