Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity

Saborni Chakraborty, Joseph C. Gonzalez, Benjamin L. Sievers, Vamsee Mallajosyula, Srijoni Chakraborty, Megha Dubey, Usama Ashraf, Bowie Yik Ling Cheng, Nimish Kathale, Kim Quyen Thi Tran, Courtney Scallan, Aanika Sinnott, Arianna Cassidy, Steven T. Chen, Terri Gelbart, Fei Gao, Yarden Golan, Xuhuai Ji, Seunghee Kim-Schulze, Mary PrahlStephanie L. Gaw, Sacha Gnjatic, Thomas U. Marron, Miriam Merad, Prabhu S. Arunachalam, Scott D. Boyd, Mark M. Davis, Marisa Holubar, Chaitan Khosla, Holden T. Maecker, Yvonne Maldonado, Elizabeth D. Mellins, Kari C. Nadeau, Bali Pulendran, Upinder Singh, Aruna Subramanian, Paul J. Utz, Robert Sherwood, Sheng Zhang, Prasanna Jagannathan, Gene S. Tan, Taia T. Wang

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.

Original languageEnglish
Article numberabm7853
JournalScience Translational Medicine
Issue number635
StatePublished - 9 Mar 2022


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