IL-13 is a driver of COVID-19 severity #MMPMID33688686
Donlan AN; Sutherland TE; Marie C; Preissner S; Bradley BT; Carpenter RM; Sturek JM; Ma JZ; Moreau GB; Donowitz JR; Buck GA; Serrano MG; Burgess SL; Abhyankar MM; Mura C; Bourne PE; Preissner R; Young MK; Lyons GR; Loomba JJ; Ratcliffe SJ; Poulter MD; Mathers AJ; Day A; Mann BJ; Allen JE; Petri WA Jr
medRxiv 2021[Mar]; ä (ä): ä PMID33688686show ga
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.
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medRxiv 2021 ; ä (ä): ä
