Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study
Romain Arrestier, Paul Bastard, Thibaut Belmondo, Guillaume Voiriot, Tomas Urbina, Charles‐Édouard Luyt, Adrian Gervais, Lucy Bizien, Lauriane Ségaux, Mariem Ben Ahmed, Raphaël Bellaïche, Tài Pham, Zakaria Ait-Hamou, Damien Roux, Raphaël Clère-Jehl, Élie Azoulay, Stèphane Gaudry, Julien Mayaux, Nicolas Fage, Hafid Ait‐Oufella, Elsa Moncomble, Mélodie Parfait, Karim Dorgham, Guy Gorochov, Armand Mekontso Dessap, Florence Canouï‐Poitrine, Jean‐Laurent Casanova, Sophie Hüe, Nicolas de Prost
Abstract
Abstract Background Auto-antibodies (auto-Abs) neutralizing type I interferons (IFN) have been found in about 15% of critical cases COVID-19 pneumonia and less than 1% of mild or asymptomatic cases. Determining whether auto-Abs influence presentation and outcome of critically ill COVID-19 patients could lead to specific therapeutic interventions. Our objectives were to compare the severity at admission and the mortality of patients hospitalized for critical COVID-19 in ICU with versus without auto-Abs. Results We conducted a prospective multicentre cohort study including patients admitted in 11 intensive care units (ICUs) from Great Paris area hospitals with proven SARS-CoV-2 infection and acute respiratory failure. 925 critically ill COVID-19 patients were included. Auto-Abs neutralizing type I IFN-α2, β and/or ω were found in 96 patients (10.3%). Demographics and comorbidities did not differ between patients with versus without auto-Abs. At ICU admission, Auto-Abs positive patients required a higher FiO 2 (100% (70–100) vs. 90% (60–100), p = 0.01), but were not different in other characteristics. Mortality at day 28 was not different between patients with and without auto-Abs (18.7 vs. 23.7%, p = 0.279). In multivariable analysis, 28-day mortality was associated with age (adjusted odds ratio (aOR) = 1.06 [1.04–1.08], p < 0.001), SOFA score (aOR = 1.18 [1.12–1.23], p < 0.001) and immunosuppression (aOR = 1.82 [1.1–3.0], p = 0.02), but not with the presence of auto-Abs (aOR = 0.69 [0.38–1.26], p = 0.23). Conclusions In ICU patients, auto-Abs against type I IFNs were found in at least 10% of patients with critical COVID-19 pneumonia. They were not associated with day 28 mortality.