Serological Analysis Reveals an Imbalanced IgG Subclass Composition Associated with COVID-19 Disease Severity [preprint]
Immunology of Infectious Disease | Infectious Disease | Virology | Virus Diseases
COVID-19 is associated with a wide spectrum of disease severity, ranging from asymptomatic 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. Through a serological analysis of serum samples from 536 convalescent healthcare workers, we found that SARS-CoV-2-specific and virus-neutralizing antibody levels were indeed elevated in individuals that experienced severe disease. The severity-associated increase in SARS-CoV-2-specific antibody was dominated by IgG, with an IgG subclass ratio skewed towards elevated receptor binding domain (RBD)- and S1-specific IgG3. However, RBD- and S1-specific IgG1, rather than IgG3 were best correlated with virus-neutralizing titers. We propose that Spike-specific IgG3 subclass utilization contributes to COVID-19 disease severity through potent Fc-mediated effector functions. These results have significant implications for SARS-CoV-2 vaccine design, and convalescent plasma therapy.
respiratory distress syndrome, Infectious Diseases, COVID-19, antibodies, SARS-CoV-2, Spike-specific IgG3
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The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
DOI of Published Version
medRxiv 2020.10.07.20208603; doi: https://doi.org/10.1101/2020.10.07.20208603. Link to preprint on medRxiv.
Yates JL, Monir E, Li Q, Wang Y, Lee WT. (2020). Serological Analysis Reveals an Imbalanced IgG Subclass Composition Associated with COVID-19 Disease Severity [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2020.10.07.20208603. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1853