Serological analysis reveals an imbalanced IgG subclass composition associated with COVID-19 disease severity
Jennifer L. Yates, Dylan Ehrbar, Danielle Hunt, Roxie C. Girardin, Alan P. Dupuis, Anne F. Payne, Mycroft Sowizral, Scott Varney, Karen E. Kulas, Valerie L. Demarest, Kelly M. Howard, Kyle Carson, Margaux Hales, Monir Ejemel, Qi Li, Yang Wang, Ruben Peredo-Wende, Ananthakrishnan Ramani, Gurpreet Singh, Klemen Strle, Nicholas J. Mantis, Kathleen A. McDonough, William T. Lee
Abstract
Coronavirus disease 2019 (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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, including virus-neutralizing titers. A serological analysis of 536 convalescent healthcare workers reveals 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 immunoglobulin G (IgG), with an IgG subclass ratio skewed toward 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.