Complement is primarily activated in the lung in a mouse model of severe COVID-19
Year: 2025
Type: article
Abstract: ) and a mouse model of COVID-19, we identify significant serologic and pulmonary complement activation post-infection. We observed C3 activation in airway and alveolar epithelia, and pulmonary vascular endothelia. Our evidence suggests the alternative pathway is the primary route of complement activation, however, components of both the alternative and classical pathways are produced locally by respiratory epithelial cells following infection, and increased in primary cultures of human airway epithelia following cytokine and SARS-CoV-2 exposure. This tissue-specific complement response appears to precede lung injury and inflammation. Our results suggest that complement activation is a defining feature of severe COVID-19 in mice, agreeing with previous publications, and provide the basis for further investigation into the role of complement in COVID-19.
Source: iScience
Authors: Peter J. Szachowicz, Christine Wohlford-Lenane, Cobey J. Donelson, Shreya Ghimire, Andrew Thurman, Biyun Xue, Timothy J. Boly, Abhishek Verma, Leila MašinoviĆ, Jennifer R. Bermick, Tayyab Rehman, Stanley Perlman, David K. Meyerholz, Alejandro A. Pezzulo, Yuzhou Zhang, Richard J.H. Smith, Paul B. McCray
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,240
Funders: Roy J. Carver Charitable Trust, National Institutes of Health, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, Topfer Family Foundation
OpenAlex ID: W4407056284