Symptomatic SARS-CoV-2 infections display specific IgG Fc structures.

Chakraborty, Saborni; Edwards, Karlie; Buzzanco, Anthony S; Memoli, Matthew J; Sherwood, Robert; Mallajosyula, Vamsee; Xie, Markus M; Gonzalez, Joseph; Buffone, Cindy; Kathale, Nimish; Providenza, Susan; Jagannathan, Prasanna; Andrews, Jason R; Blish, Catherine A; Krammer, Florian; Dugan, Haley; Wilson, Patrick C; Pham, Tho D; Boyd, Scott D; Zhang, Sheng; Taubenberger, Jeffery K; Morales, Tasha; Schapiro, Jeffrey M; Parsonnet, Julie; Wang, Taia T

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a public health crisis that is exacerbated by our poor understanding of correlates of immunity. SARS-CoV-2 infection can cause Coronavirus Disease 2019 (COVID-19), with a spectrum of symptoms ranging from asymptomatic carriage to life threatening pneumonia and cytokine dysregulation [1-3]. Although antibodies have been shown in a variety of in vitro assays to promote coronavirus infections through mechanisms requiring interactions between IgG antibodies and Fc gamma receptors (FcγRs), the relevance of these observations to coronavirus infections in humans is not known [4-7]. In light of ongoing clinical trials examining convalescent serum therapy for COVID-19 patients and expedited SARS-CoV-2 vaccine testing in humans, it is essential to clarify the role of antibodies in the pathogenesis of COVID-19. Here we show that adults with PCR-diagnosed COVID-19 produce IgG antibodies with a specific Fc domain repertoire that is characterized by reduced fucosylation, a modification that enhances interactions with the activating FcγR, FcγRIIIa. Fc fucosylation was reduced when compared with SARS-CoV-2-seropositive children and relative to adults with symptomatic influenza virus infections. These results demonstrate an antibody correlate of symptomatic SARS-CoV-2 infections in adults and have implications for novel therapeutic strategies targeting FcγRIIIa pathways.