Proinflammatory IgG Fc structures in patients with severe COVID-19
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Abstract
Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.
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Antibodies that promote inflammation might contribute to cytokine storm and severe disease.
“On the other hand, antibodies promoting inflammatory responses may contribute to a cytokine storm resulting in severe disease32,33.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [32]
The possible role of IgG with reduced Fc fucosylation and stronger FcγRIII binding in severe COVID-19 suggests that vaccine-induced antibody quality may matter for minimizing ADE risk.
“However, the potential role of IgG with reduced Fc fucosylation and enhanced binding to FcγRIII in the development of severe COVID-19 suggests that the quality of antibodies induced by vaccination may also be important in minimizing the risk of ADE32,33.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [32]
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- Authors
- Chakraborty, S., Gonzalez, J., Edwards, K., Mallajosyula, V., Buzzanco, A. S., Sherwood, R., Buffone, C., Kathale, N., Providenza, S., Xie, M. M., Andrews, J. R., Blish, C. A., Singh, U., Dugan, H., Wilson, P. C., Pham, T. D., Boyd, S. D., Nadeau, K. C., Pinsky, B. A., Zhang, S., Memoli, M. J., Taubenberger, J. K., Morales, T., Schapiro, J. M., Tan, G. S., Jagannathan, P., & Wang, T. T.
- Affiliations
- Stanford Medicine (US)
- Stanford University (US)
- Cornell University (US)
- Chan Zuckerberg Biohub San Francisco (US)
- University of Chicago (US)
- Stanford Blood Center (US)
- National Institutes of Health (US)
- Kaiser Permanente Northern California (US)
- J. Craig Venter Institute (US)
- Corresponding author
- Wang, Taia T.
- ORCID
- Chakraborty, Saborni
- Edwards, Karlie
- Mallajosyula, Vamsee
- Buzzanco, Anthony S.
- Buffone, Cindy
- Xie, Markus M.
- Andrews, Jason R.
- Blish, Catherine A.
- Singh, Upinder
- Dugan, Haley
- Wilson, Patrick C.
- Pham, Tho D.
- Boyd, Scott D.
- Nadeau, Kari C.
- Pinsky, Benjamin A.
- Zhang, Sheng
- Memoli, Matthew J.
- Taubenberger, Jeffery K.
- Tan, Gene S.
- Jagannathan, Prasanna
- Wang, Taia T.
- Venue
- Nature Immunology
- Published
- 2020-11-09
- Volume
- 22
- Issue
- 1
- Pages
- 67-73
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC8130642
- OpenAlex
- W3105885548
- Cited by
- 326
- References
- 41
- Citations by year
- 2026: 25 · 2025: 35 · 2024: 32 · 2023: 41 · 2022: 98 · 2021: 83 · 2020: 12
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Immunology (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, cc-by)
- PubMed Central (acceptedVersion)
- PubMed Central (submittedVersion)
- ImmPort
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R01AI139119, U54CA260517, U19AI111825)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- severe COVID-19, SARS-CoV-2, IgG1, Fc glycan, afucosylation, FcγRIIIa, Fcγ receptor binding, immune complexes, monocytes, interleukin-6, TNF-α, hyperinflammation, disease severity
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