| IL-13 is a driver of COVID-19 severity William A. Petri1; 1UNIVERSITY OF VIRGINIA, Charlottesville, United States; PAPER: 211/covid19/Plenary (Oral) SCHEDULED: 11:30/Wed. 30 Nov. 2022/Ballroom B ABSTRACT: SARS-CoV-2 is currently causing the global COVID-19 pandemic, and understanding mechanisms that contribute to severity will aid in protection from poor outcomes. Here we report that increased interleukin-13 (IL-13) was associated with the need for mechanical ventilation in two independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed the IL-13 and IL-4 receptor blocker, Dupilumab, had less severe disease. In SARS-CoV-2 infected mice, IL-13 neutralization resulted in reduced disease severity, demonstrating a pathogenic role for this cytokine. Following IL-13 blockade, hyaluronan synthase 1, Has1 was identified as the most highly downregulated gene. Furthermore, blocking of the hyaluronan receptor, CD44, reduced mortality in infected mice, suggesting this pathway is regulated by IL-13. Understanding the role of IL-13 and hyaluronan has important implications for therapy of COVID-19 and potentially other pulmonary diseases. |
