2023-Sustainable Industrial Processing Summit
Guerrant Intl. Symp /Covid-19 and Infectious Diseases
| Editors: | F. Kongoli, F. Murad, W. Petri, H. Inufusa, S. Heysell, J. Yedoyan |
| Publisher: | Flogen Star OUTREACH |
| Publication Year: | 2023 |
| Pages: | 92 pages |
| ISBN: | 978-1-989820-80-3 (CD) |
| ISSN: | 2291-1227 (Metals and Materials Processing in a Clean Environment Series) |
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ROLE OF TYPE 2 IMMUNITY IN COVID-19
William Petri Jr1;1UNIVERSITY OF VIRGINIA, Charlottesville, United States;
Type of Paper: Regular
Id Paper: 233
Topic: 68
Abstract:
Introduction: We discovered that IL-13 is elevated in patients with COVID-19, promoted disease in a mouse model, and in a RCT showed that IL-13/IL-4 blockade with dupilumab (anti-IL4Ra mAb) reduced mortality in patients with COVID-19. IL-13 induces the deposition of the polysaccharide hyaluronan (HA) in the lungs, and inhibition of the HA receptor CD44 protects from SARS-CoV-2 disease. We are determining the mechanisms by which alarmins such as IL-33 initiate a type 2 immune response, how IL-13 is induced, and its impact on HA matrices and CD44-mediated inflammation and disease.
Hypothesis: We hypothesize that IL-13 produced by ILC2s in the lung during COVID-19 induces a hyaluronan (HA) matrix that via HA receptors (including CD44+) recruits inflammatory cells, resulting in respiratory failure.
Significance: Uncovering the mechanisms of IL-13-induced hyaluronan matrices and signaling in driving COVID-19 severity has the promise of novel therapeutic approaches directed at the IL-13 - hyaluronan pathway, as well as being of importance for other pulmonary diseases where hyaluronan is known to contribute.
Keywords:
Coronavirus; Infectious Diseases; Respiratory DiseasesReferences:
[1] 1. Sasson J, Donlan AN, Ma JZ, Haughey HM, Coleman R, Nayak U, Mathers AJ, Laverdure S, Dewar R, Jackson PEH, Heysell SK, Sturek JM, Petri WA Jr. Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019: A Phase 2a Trial. Open Forum Infect Dis. 2022 Jul 27;9(8):ofac343. doi: 10.1093/ofid/ofac343. PMID: 35959207; PMCID: PMC9361171.[2] 2. 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. IL-13 is a driver of COVID-19 severity. JCI Insight. 2021 Jun 29; PMID: 33688686