SARS-CoV-2 Immune Complex–Mediated Neutrophil Activation
Understanding disease pathogenesis is essential to developing therapies in patients with infections that cause critical illness. Herein, we show that SARS-CoV-2-specific antibody levels and markers of neutrophil activation are associated with disease severity in patients hospitalized with COVID-19. We also provide a link between the adaptive and innate immune response by demonstrating an association between antibody levels and multiple markers of neutrophil degranulation and NETosis. We further demonstrate through a series of in vitro assays that SARS-CoV-2 antigen-antibody immune complexes can stimulate NETosis. Last, we discuss how this NETosis is more strongly associated with IgA immune complexes than IgG and can be ameliorated with spleen tyrosine kinase inhibition.
Authors
- Daniel S. Chertow (ORCID: https://orcid.org/0000-0002-1675-1728)
- Jeffrey I. Cohen (ORCID: https://orcid.org/0000-0003-0238-7176)
- Anthony F. Suffredini (ORCID: https://orcid.org/0000-0003-4179-0902)
- Bindu Parachalil Gopalan (ORCID: https://orcid.org/0000-0001-9616-1367)
- Kiana C Allen (ORCID: https://orcid.org/0009-0009-1182-5749)
- Marcos Javier Ramos-Benítez (ORCID: https://orcid.org/0000-0001-9445-3294)
- Peter D. Burbelo (ORCID: https://orcid.org/0000-0003-1717-048X)
- Christopher S. King (ORCID: https://orcid.org/0000-0003-3101-319X)
- Xin Tian (ORCID: https://orcid.org/0000-0003-1896-2462)
- Steven D. Nathan (ORCID: https://orcid.org/0000-0002-6270-1617)
- Seth Warner (ORCID: https://orcid.org/0009-0001-4571-9188)
- Rui Miao (ORCID: https://orcid.org/0000-0001-5046-6341)
- Jeffrey R. Strich (ORCID: https://orcid.org/0000-0002-5671-1130)
- Yogendra Kanthi (ORCID: https://orcid.org/0000-0002-5660-5194)
- Heather Teague (ORCID: https://orcid.org/0000-0001-6013-4252)
- Robert Reger
- C Pang
- Richard Childs
Institutions
- Office of the Secretary of Defense (US)
- National Institutes of Health (US)
- United States Department of Defense (US)
- Ponce Health Sciences University (PR)
- Inova Fairfax Hospital (US)
- National Institute of Dental and Craniofacial Research (US)
- National Heart, Lung, and Blood Institute (US)
- National Institute of Allergy and Infectious Diseases (US)
- National Institutes of Health Clinical Center (US)
Publication Details
- Journal
- Open Forum Infectious Diseases
- Published
- 2025-03-27
- DOI
- https://doi.org/10.1093/ofid/ofaf199
- Citations
- 3
- Primary Topic
- COVID-19 Clinical Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 4.19