IL-13 is a driver of COVID-19 severity

Donlan, Alexandra N.; Sutherland, Tara E.; Marie, Chelsea; Preissner, Saskia; Bradley, Ben T.; Carpenter, Rebecca M.; Sturek, Jeffrey M.; Ma, Jennie Z.; Moreau, G. Brett; Donowitz, Jeffrey R.; Buck, Gregory A.; Serrano, Myrna G.; Burgess, Stacey L.; Abhyankar, Mayuresh M.; Mura, Cameron; Bourne, Philip E.; Preissner, Robert; Young, Mary K.; Lyons, Genevieve R.; Loomba, Johanna J.; Ratcliffe, Sarah J; Poulter, Melinda D.; Mathers, Amy J.; Day, Anthony; Mann, Barbara J.; Allen, Judith E.; Petri, William A.

Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here we report that elevated 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 Dupilumab had less severe disease. In SARS-CoV-2 infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti-IL-13 treatment in infected mice, in the lung, hyaluronan synthase 1 (Has1) was the most downregulated gene and hyaluronan accumulation was decreased. Blockade of the hyaluronan receptor, CD44, reduced mortality in infected mice, supporting the importance of hyaluronan as a pathogenic mediator, and indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and hyaluronan has important implications for therapy of COVID-19 and potentially other pulmonary diseases.