@article {995, title = {Neutralizing Autoantibodies to Type I IFNs in >10\% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain.}, journal = {J Clin Immunol}, year = {2021}, month = {2021 Apr 13}, abstract = {

BACKGROUND: In a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10\% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I IFNs but rarely IFN-beta.

OBJECTIVES: We aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes.

METHODS: We analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFN-beta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain.

RESULTS: The cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34\%) had a critical progression requiring ICU admission. The median age was 71~years, with 28 men (58.6\%). Type I IFN-alpha- and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6\%), while they were not found in any of the 118 asymptomatic controls (p = 0.0016). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (p = 5.10e) and lower lymphocyte counts (p = 1.80e). No significant association with response to IFN-beta-1b therapy (p = 0.34) was found. Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80\% vs 12/42, 28.5\%).

CONCLUSION: Autoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10\% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted.

}, issn = {1573-2592}, doi = {10.1007/s10875-021-01036-0}, author = {Troya, Jes{\'u}s and Bastard, Paul and Planas-Serra, Laura and Ryan, Pablo and Ruiz, Montse and de Carranza, Mar{\'\i}a and Torres, Juan and Mart{\'\i}nez, Amalia and Abel, Laurent and Casanova, Jean-Laurent and Pujol, Aurora} }