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

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

Bastard P,Vazquez S,Liu J,Laurie M,Wang C,Gervais A,Le Voyer T,Bizien L,Zamecnik C,Philippot Q,Rosain J,Catherinot E,Willmore A,Mitchell A,Bair R,Garçon P,Kenney H,Fekkar A,Salagianni M,Poulakou G,Siouti E,Sahanic S,Tancevski I,Weiss G,Nagl L,Manry J,Duvlis S,Arroyo-Sánchez D,Paz Artal E,Rubio L,Perani C,Bezzi M,Sottini A,Quaresima V,Roussel L,Vinh D,Reyes L,Garzaro M,Hatipoglu N,Boutboul D,Tandjaoui-Lambiotte Y,Borghesi A,Aliberti A,Cassaniti I,Venet F,Monneret G,Halwani R,Sharif-Askari N,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,Antolí A,Jeziorski E,Rocamora-Blanch G,Teixeira C,Delaunay C,Lhuillier M,Le Turnier P,Zhang Y,Mahevas M,Pan-Hammarström Q,Abolhassani H,Bompoil T,Dorgham K,Gorochov G,Laouenan C,Rodríguez-Gallego C,Ng L,Renia L,Pujol A,Belot A,Raffi F,Allende L,Martinez-Picado J,Ozcelik T,Imberti L,Notarangelo L,Troya J,Solanich X,Zhang S,Puel A,Wilson M,Trouillet-Assant S,Abel L,Jouanguy E,Ye C,Cobat A,Thompson L,Andreakos E,Zhang Q,Anderson M,Casanova J,DeRisi J

Source :

2023 Déc 22

Pmid / DOI:

35857576

Abstract

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-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. 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.

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