Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Bastard, P.; Vazquez, S. E.; Liu, J.; Laurie, M. T.; Wang, C. Y.; Gervais, A.; Voyer, T. L.; Bizien, L.; Zamecnik, C.; Philippot, Q.; Rosain, J.; Catherinot, E.; Willmore, A.; Mitchell, A. M.; Bair, R.; Garcon, P.; Kenney, H.; Fekkar, A.; Salagianni, M.; Poulakou, G.; Siouti, E.; Sahanic, S.; Tancevski, I.; Weiss, G.; Nagl, L.; Manry, J.; Duvlis, S.; Arroyo-Sanchez, D.; Artal, E. P.; Rubio, L.; Perani, C.; Bezzi, M.; Sottini, A.; Quaresima, V.; Roussel, L.; Vinh, D. C.; Reyes, L. F.; Garzaro, M.; Hatipoglu, N.; Boutboul, D.; Tandjaoui-Lambiotte, Y.; Borghesi, A.; Aliberti, A.; Cassaniti, I.; Venet, F.; Monneret, G.; Halwani, R.; Sharif-Askari, N. S.; Danielson, J.; Burrel, S.; Morbieu, C.; Stepanovskyy, Y.; Bondarenko, A.; Volokha, A.; Boyarchuk, O.; Gagro, A.; Neuville, M.; Neven, B.; Keles, S.; Hernu, R.; Bal, A.; Novelli, A.; Novelli, G.; Saker, K.; Ailioaie, O.; Antoli, A.; Jeziorski, E.; Rocamora-Blanch, G.; Teixeira, C.; Delaunay, C.; Lhuillier, M.; Turnier, P. L.; Zhang, Y.; Mahevas, M.; Pan-Hammarstrom, Q.; Abolhassani, H.; Bompoil, T.; Dorgham, K.; Gorochov, G.; Laouenan, C.; Rodriguez-Gallego, C.; L. F. P., Ng; Renia, L.; Pujol, A.; Belot, A.; Raffi, F.; Allende, L. M.; Martinez-Picado, J.; Ozcelik, T.; Imberti, L.; Notarangelo, L. D.; Troya, J.; Solanich, X.; Zhang, S. -Y.; Puel, A.; Wilson, M. R.; Trouillet-Assant, S.; Abel, L.; Jouanguy, E.; C. J., Ye; Cobat, A.; Thompson, L. M.; Andreakos, E.; Zhang, Q.; Anderson, M. S.; Casanova, J. -L.; Derisi, J. L.; Achille, C.; Aiuti, A.; Al-Muhsen, S.; Al-Mulla, F.; Angelini, M.; Arias, A. A.; Aytekin, G.; Baldanti, F.; Banos, A.; Feldman, H. B.; Bergami, F.; Biggs, C. M.; Bogunovic, D.; Bolze, A.; Bousfiha, A. A.; Brodin, P.; Bryceson, Y.; Bustamante, C. D.; Butte, M. J.; Casari, G.; Christodoulou, J.; Clement, B.; Condino-Neto, A.; Constantinescu, S. N.; Conti, F.; Cooper, M. A.; Daganou, M.; Dalgard, C. L.; Desai, M.; Drolet, B. A.; El Baghdadi, J.; Ergun, R.; Ergun, D.; Espinosa-Padilla, S.; Fellay, J.; Flores, C.; Franco, J. L.; Froidure, A.; Ghirardello, S.; Gregersen, P. K.; Grimbacher, B.; Haerynck, F.; Hagin, D.; Hammarstrom, L.; Heath, J. R.; Henrickson, S. E.; Hsieh, E. W. Y.; Husebye, E.; Imai, K.; Itan, Y.; Jarvis, E. D.; Kanat, F.; Karamitros, T.; Kisand, K.; Kopcha, V.; Korda, M.; C. -L., Ku; Lampropoulou, V.; Lau, Y. -L.; Ling, Y.; Lucas, C. L.; Maniatis, T.; Mansouri, D.; Marodi, L.; Meyts, I.; Milner, J. D.; Mironska, K.; Mogensen, T. H.; Mojoli, F.; Morandeira, F.; Morio, T.; O'Farrelly, C.; Okada, S.; Okamoto, K.; Pagani, M.; Papadaki, M.; Pape, J. W.; De Diego, R. P.; Perlin, D. S.; Pesole, G.; Pession, A.; Piralla, A.; Pirounaki, M.; Planas, A. M.; Prando, C.; Quintana-Murci, L.; Ramaswamy, S.; Rapti, V.; Resnick, I.; Rigo-Bonnin, R.; Sancho-Shimizu, V.; Sediva, A.; Seppanen, M. R. J.; Shahrooei, M.; Shcherbina, A.; Slaby, O.; Snow, A. L.; Soler-Palacin, P.; Spaan, A. N.; Syrigos, K.; Tangye, S. G.; Tayoun, A. A.; Triantafyllia, V.; Tsiodras, S.; Tulek, B.; Turvey, S. E.; Furkan Uddin, K. M.; Uddin, M. J.; Van De Beek, D.; Vatansev, H.; Von Bernuth, H.; Wauters, J.; Zatz, M.; Zawadzki, P.; Gok, F.; Emiroglu, M.; Alkan, G.; Yormaz, B.

doi:10.1126/sciimmunol.abp8966

Life-threatening "breakthrough"cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-a2 and IFN-w, whereas two neutralized IFN-w only. No patient neutralized IFN-b. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs / Bastard, P., Vazquez, S.E., Liu, J., Laurie, M.T., Wang, C.Y., Gervais, A., Voyer, T.L., Bizien, L., Zamecnik, C., Philippot, Q., Rosain, J., Catherinot, E., Willmore, A., Mitchell, A.M., Bair, R., Garcon, P., Kenney, H., Fekkar, A., Salagianni, M., Poulakou, G., et al.. - In: SCIENCE IMMUNOLOGY. - ISSN 2470-9468. - 8:90(2023). [10.1126/sciimmunol.abp8966]