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

Abers, Michael S; Rosen, Lindsey B; Delmonte, Ottavia M; Shaw, Elana; Bastard, Paul; Imberti, Luisa; Quaresima, Virginia; Biondi, Andrea; Bonfanti, Paolo; Castagnoli, Riccardo; Casanova, Jean‐Laurent; Su, Helen C; Notarangelo, Luigi D; Holland, Steven M; Lionakis, Michail S

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.