Neutralizing type-I interferon autoantibodies are associated with delayed viral clearance and intensive care unit admission in patients with COVID-19

Abstract

Type-I interferons (IFNs) mediate antiviral activity and have emerged as important immune mediators during coronavirus disease 19 (COVID-19). Several lines of evidence suggest that impaired type-I IFN signaling may predispose to severe COVID-19. However, the pathophysiologic mechanisms that contribute to illness severity remain unclear. In this study, our goal was to gain insight into how type-I IFNs influence outcomes in patients with COVID-19. To achieve this goal, we compared clinical outcomes between 26 patients with neutralizing type-I IFN autoantibodies (AAbs) and 192 patients without AAbs who were hospitalized for COVID-19 at three Italian hospitals. The presence of circulating AAbs to type-I IFNs was associated with an increased risk of admission to the intensive care unit and a delayed time to viral clearance. However, survival was not adversely affected by the presence of type-I IFN AAbs. Our findings provide further support for the role of type-I IFN AAbs in impairing host antiviral defense and promoting the development of critical COVID-19 pneumonia in severe acute respiratory syndrome coronavirus 2-infected individuals.

Keywords: Immunological deficiency syndromes; infectious diseases; innate immunity; translational immunology; viral infection.

Figure 1

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) clearance, admission to the intensive care unit (ICU) and survival in coronavirus disease 19 (COVID‐19) patients with versus without autoantibodies (AAbs) to type‐I interferons (IFNs). (a) Proportion of all patients testing positive for SARS‐CoV‐2 by PCR nasal swab test during the course of illness in patients with (n = 17) versus without (n = 102) AAbs to type‐I IFNs. (b) Proportion of patients testing positive for SARS‐CoV‐2 by PCR nasal swab test during the course of illness in a subset of patients who required ICU care with (n = 11) versus without (n = 50) AAbs to type‐I IFNs. (c) Severity of illness in patients with (n = 26) versus without (n = 192) AAbs to type‐I IFNs. P = 0.012 by a Chi‐squared test. (d) Cumulative incidence of ICU admission during the first 2 weeks of hospitalization in patients with (n = 25, including 3 admitted to ICU within 24 h of hospitalization) versus without (n = 190, including 16 admitted to ICU within 24 h of hospitalization) AAbs to type‐I IFNs. Data on the timing of ICU admission relative to hospital admission were not available for three patients. (e) Kaplan–Meier plot displaying survival during the 10‐week period following hospital admission in patients admitted to the ICU (n = 75) versus those not admitted to the ICU (n = 143). (f) Kaplan–Meier plot displaying survival during the 10‐week period following hospital admission in patients with (n = 26) versus without (n = 192) AAbs to type‐I IFNs. “No. at risk” in panels a–c refers to the number of patients in each group [AAb positive (AAb+) or AAb negative (AAb−)] who were alive at the specified time point. CI, confidence interval.