Proinflammatory IgG Fc structures in patients with severe COVID-19 (original) (raw)

, Joseph Gonzalez, Karlie Edwards, Vamsee Mallajosyula, Anthony S. Buzzanco, Robert Sherwood, View ORCID ProfileCindy Buffone, Nimish Kathale, Susan Providenza, View ORCID ProfileMarkus M. Xie, Jason R. Andrews, Catherine A. Blish, Upinder Singh, Haley Dugan, Patrick C. Wilson, Tho D. Pham, Scott D. Boyd, Kari C. Nadeau, View ORCID ProfileBenjamin A. Pinsky, Sheng Zhang, Matthew J. Memoli, Jeffery K. Taubenberger, Tasha Morales, Jeffrey M. Schapiro, Gene S. Tan, Prasanna Jagannathan, Taia T. Wang

doi: https://doi.org/10.1101/2020.05.15.20103341

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-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 severe COVID-19 patients produced a unique serologic signature, including increased IgG1 with afucosylated Fc glycans. This Fc modification on SARS-CoV-2 IgGs enhanced interactions with the activating FcγR, FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including IL-6 and TNF. These results show that disease severity in COVID-19 correlates with the presence of afucosylated IgG1, a pro-inflammatory IgG Fc modification.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Support was received from Stanford University, the Chan Zuckerberg Biohub and the Searle Scholars Program. Research reported in this publication was supported by Fast Grants, CEND COVID Catalyst Fund, the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Numbers U19AI111825, U54CA260517 and R01AI139119, R01AI130398 and R01AI127877. Clinical samples were obtained with support from the Rockefeller University Center for Clinical and Translational Science Grant # UL1 TR001866.

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Institutional Review Board of Stanford University, Institutional Review Board of Rockefeller University, Institutional Review Boards of the Makerere University School of Biomedical Sciences, the Uganda National Council for Science and Technology, and the University of California San Francisco, Nepal Health Research Council, Kathmandu University Institutional Review Board

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Data Availability

All raw data are available from the corresponding author on reasonable request.