COVID-19 Severity Is Associated with Differential Antibody Fc-Mediated Innate Immune Functions.

Abstract

Beyond neutralization, antibodies binding to their Fc receptors elicit several innate immune functions including antibody-dependent complement deposition (ADCD), antibody-dependent cell-mediated phagocytosis (ADCP), and antibody-dependent cell-mediated cytotoxicity (ADCC). These functions are beneficial, as they contribute to pathogen clearance; however, they also can induce inflammation. We tested the possibility that qualitative differences in SARS-CoV-2-specific antibody-mediated innate immune functions contribute to coronavirus disease 2019 (COVID-19) severity. We found that anti-S1 and anti-RBD antibodies from hospitalized COVID-19 patients elicited higher ADCD but lower ADCP compared to antibodies from nonhospitalized COVID-19 patients. Consistently, higher ADCD was associated with higher systemic inflammation, whereas higher ADCP was associated with lower systemic inflammation during COVID-19. Our study points to qualitative, differential features of anti-SARS-CoV-2 specific antibodies as potential contributors to COVID-19 severity. Understanding these qualitative features of natural and vaccine-induced antibodies will be important in achieving optimal efficacy and safety of SARS-CoV-2 vaccines and/or COVID-19 therapeutics.IMPORTANCE A state of hyperinflammation and increased complement activation has been associated with coronavirus disease 2019 (COVID-19) severity. However, the pathophysiological mechanisms that contribute to this phenomenon remain mostly unknown. Our data point to a qualitative, rather than quantitative, difference in SARS-CoV-2-specific antibodies' ability to elicit Fc-mediated innate immune functions as a potential contributor to COVID-19 severity and associated inflammation. These data highlight the need for further studies to understand these qualitative features and their potential contribution to COVID-19 severity. This understanding could be essential to develop antibody-based COVID-19 therapeutics and SARS-CoV-2 vaccines with an optimal balance between efficacy and safety.

• Authors: Opeyemi S Adeniji, Leila B Giron, Mansi Purwar, Netanel F Zilberstein, Abhijeet J Kulkarni, Maliha W Shaikh, Robert A Balk, James N Moy, Christopher B Forsyth, Qin Liu, Harsh Dweep, Andrew Kossenkov, David B Weiner, Ali Keshavarzian, Alan Landay, Mohamed Abdel-Mohsen
• Journal: mBio (mBio) Vol. 12 Issue 2 (04 20 2021) ISSN: 2150-7511 [Electronic] United States
• PMID: 33879594 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Adeniji et al.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Biomarkers
• Immunoglobulin Fc Fragments
• Receptors, Fc
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2

Topics

• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood, immunology)
• Antibody Specificity
• Antibody-Dependent Cell Cytotoxicity
• Biomarkers (blood)
• COVID-19 (etiology, immunology, virology)
• Case-Control Studies
• Cohort Studies
• Complement Activation
• Female
• Humans
• Immunity, Innate
• Immunoglobulin Fc Fragments (immunology)
• Inflammation (blood, etiology, immunology)
• Male
• Middle Aged
• Pandemics
• Phagocytosis
• Receptors, Fc (immunology)
• SARS-CoV-2 (immunology)
• Severity of Illness Index
• Spike Glycoprotein, Coronavirus (immunology)