Auto-antibodies against type I IFNs in > 10% of critically ill COVID-19 patients: a prospective multicentre study

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 FiO2 (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.

High frequency of type I interferon auto‐antibodies in a group of middle‐aged HIV‐infected patients: A cross‐sectional exploratory study

“…Several other compelling studies have confirmed the link between IFN‐I auto‐Abs and COVID‐19 severity as reported by Arrestier et al 15 Currently, the presence of those auto‐Abs are waking up interest in the course of other infections. Very recent data reported that they are present in about 5% of cases of life‐threatening influenza pneumonia 16 .…”

“…14 Their presence was considered to be clinically silent in general population until the COVID-19 pandemic onset, when it was correlated to severity of COVID-19, mainly in males over 65 years old. 3 Several other compelling studies have confirmed the link between IFN-I auto-Abs and COVID-19 severity as reported by Arrestier et al 15 Currently, the presence of those auto-Abs are waking up interest in the course of other infections. Very recent data reported that they are present in about 5% of cases of life-threatening influenza pneumonia.…”

A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade

“…Big data analyses revealed interferon deficiency, inborn errors in IFN signaling and autoantibodies to Type I IFN in severely ill patients. The latter accounts for more than 10% of these patients ( 36 – 42 ).…”

High-Dose Steroids for Nonresolving Acute Respiratory Distress Syndrome in Critically Ill COVID-19 Patients Treated With Dexamethasone: A Multicenter Cohort Study*

“…This is an ancillary analysis of the Pronostic Value of Type I ANTi-Interferon Antibodies in Patients With COVID-19 Acute Respiratory Failure (ANTICOV) study (19). It was a multicenter prospective observational cohort in 11 ICUs of Great Paris area's hospitals aimed to determine the association of auto-antibodies neutralizing type I interferons with mortality in critically ill patients with COVID-19.…”