Alexandra N Donlan, Tara E Sutherland, Chelsea Marie, Saskia Preissner, Benjamin T Bradley, Rebecca M Carpenter, Jeffrey M Sturek, Jennie Z Ma, G Brett Moreau, Jeffrey R Donowitz, Gregory A Buck, Myrna G Serrano, Stacey L Burgess, Mayuresh M Abhyankar, Cameron Mura, Philip E Bourne, Robert Preissner, Mary K Young, Genevieve R Lyons, Johanna J Loomba, Sarah J Ratcliffe, Melinda D Poulter, Amy J Mathers, Anthony J Day, Barbara J Mann, Judith E Allen, William A Petri
Author Information
Alexandra N Donlan: Division of Infectious Diseases and International Health, Department of Medicine and.
Tara E Sutherland: Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom.
Chelsea Marie: Division of Infectious Diseases and International Health, Department of Medicine and.
Saskia Preissner: Department Oral and Maxillofacial Surgery, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Benjamin T Bradley: Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
Rebecca M Carpenter: Division of Infectious Diseases and International Health, Department of Medicine and.
Jeffrey M Sturek: Division of Pulmonary and Critical Care Medicine, Department of Medicine and.
Jennie Z Ma: Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
G Brett Moreau: Division of Infectious Diseases and International Health, Department of Medicine and.
Jeffrey R Donowitz: Division of Infectious Diseases and International Health, Department of Medicine and.
Gregory A Buck: Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
Myrna G Serrano: Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
Stacey L Burgess: Division of Infectious Diseases and International Health, Department of Medicine and.
Mayuresh M Abhyankar: Division of Infectious Diseases and International Health, Department of Medicine and.
Cameron Mura: School of Data Science and Department of Biomedical Engineering University of Virginia, Charlottesville, Virginia, USA.
Philip E Bourne: School of Data Science and Department of Biomedical Engineering University of Virginia, Charlottesville, Virginia, USA.
Robert Preissner: Science-IT and Institute of Physiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Mary K Young: Division of Infectious Diseases and International Health, Department of Medicine and.
Genevieve R Lyons: Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Johanna J Loomba: Integrated Translational Health Research Institute (iTHRIV) and.
Sarah J Ratcliffe: Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Melinda D Poulter: Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Amy J Mathers: Division of Infectious Diseases and International Health, Department of Medicine and.
Anthony J Day: Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom.
Barbara J Mann: Division of Infectious Diseases and International Health, Department of Medicine and.
Judith E Allen: Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom.
William A Petri: Division of Infectious Diseases and International Health, Department of Medicine and.
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 IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, 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, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13-induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13-mediated HA synthesis in pulmonary pathology.
