1. FcγRIIa-mediated antibody-dependent uptake of SARS-CoV-2 enhances IL-6 expression of monocytes.
- Author
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Mese, Kemal, Maguilla Rosado, Esther, Lüder, Carsten G.K., Abdel-Moneim, Ahmed Sayed, Jordan, Patrick, Schwanbeck, Julian, Bunz, Oskar, Lugert, Raimond, Bohne, Wolfgang, Gao, Jian, Dudakova, Anna, Groß, Uwe, and Zautner, Andreas E.
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MONONUCLEAR leukocytes ,COVID-19 ,COVID-19 pandemic ,VIRAL antibodies ,SARS-CoV-2 - Abstract
This work aimed to investigate interactions between antibody-opsonized SARS-CoV-2 and monocytes enriched from human peripheral blood mononuclear cells (PBMC) to determine whether antibody dependent enhancement might contribute to the pathophysiology of COVID-19. Pre-incubation of SARS-CoV-2 with sera from hospitalized COVID-19 patients led to significantly increased virus uptake and viral replication in monocytes. Remarkably, SARS-CoV-2 pre-incubated with sera from patients with severe COVID-19 but not those with mild disease or post vaccination strongly increased IL-6 secretion by monocytes. Antibody dependent viral uptake was partially inhibited by monoclonal anti-FcγRIIa antibody whereas IL-6 secretion was completely abolished. FcγRIIa preferentially binds IgG2, and sera from patients with severe COVID-19 contained lower IgG2 levels as compared to mild COVID-19 cases whereas IgG1 levels were increased. These data suggests that FcγRIIa-mediated binding of antibody-opsonized SARS-CoV-2 critically impacts monocytic inflammatory cytokine release and COVID-19 pathophysiology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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