Abstract
BackgroundIn 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.ObjectivesWe 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.MethodsWe 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.ResultsThe 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−03) and lower lymphocyte counts (p = 1.80e−02). 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%).ConclusionAutoantibodies 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.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10875-021-01036-0.
Highlights
In December 2019, infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, China
A total of 47 adult patients with severe COVID-19 and with a positive nasopharyngeal swab PCR test for SARS-CoV-2 who were treated with IFN-beta-1b (Betaferon) were included in the study and assayed for the presence of neutralizing autoantibodies against type I IFN in plasma, as described by Bastard P et al [6], (Fig. 1)
High C-reactive protein and ferritin concentrations and low lymphocyte counts have been repeatedly identified as risk predictors of severity and mortality [21,22,23]
Summary
In December 2019, infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, China. In approximately 3% of subjects, SARSCoV-2 infection results in pneumonia, which in approximately 0.3% of subjects evolves into acute respiratory distress syndrome (ARDS) with systemic inflammation [2]. 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
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