Author: Yates, Jennifer L.; Ehrbar, Dylan J.; Hunt, Danielle T.; Girardin, Roxanne C.; Dupuis, Alan P.; Payne, Anne F.; Sowizral, Mycroft; Varney, Scott; Kulas, Karen E.; Demarest, Valerie L.; Howard, Kelly M.; Carson, Kyle; Hales, Margaux; Ejemel, Monir; Li, Qi; Wang, Yang; Peredo-Wende, Ruben; Ramani, Ananthakrishnan; Singh, Gurpreet; Strle, Klemen; Mantis, Nicholas J.; McDonough, Kathleen A.; Lee, William T.
Title: Serological Analysis Reveals an Imbalanced IgG Subclass Composition Associated with COVID-19 Disease Severity Cord-id: 6gzdrti9 Document date: 2021_6_15
ID: 6gzdrti9
Snippet: COVID-19 is associated with a wide spectrum of disease presentation, ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity and the levels of circulating SARS-CoV-2-specific antibodies, including virus neutralizing titers. A serological analysis of 536 convalescent healthcare workers reveal that SARS-CoV-2-specific and virus-neutralizing antibody levels are elevated in individual
Document: COVID-19 is associated with a wide spectrum of disease presentation, ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity and the levels of circulating SARS-CoV-2-specific antibodies, including virus neutralizing titers. A serological analysis of 536 convalescent healthcare workers reveal that SARS-CoV-2-specific and virus-neutralizing antibody levels are elevated in individuals that experience severe disease. The severity-associated increase in SARS-CoV-2-specific antibody is dominated by IgG, with an IgG subclass ratio skewed towards elevated receptor binding domain (RBD)- and S1-specific IgG3. In addition, individuals that experience severe disease show elevated SARS-CoV-2 specific antibody binding to the inflammatory receptor FcɣRIIIa. Based on these correlational studies, we propose that Spike-specific IgG subclass utilization may contribute to COVID-19 disease severity through potent Fc-mediated effector functions. These results may have significant implications for SARS-CoV-2 vaccine design and convalescent plasma therapy.
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