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

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. Beyond neutralization, antibodies binding to their Fc receptors...

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Published in:mBio Vol. 12; no. 2
Main Authors: Adeniji, Opeyemi S., Giron, Leila B., Purwar, Mansi, Zilberstein, Netanel F., Kulkarni, Abhijeet J., Shaikh, Maliha W., Balk, Robert A., Moy, James N., Forsyth, Christopher B., Liu, Qin, Dweep, Harsh, Kossenkov, Andrew, Weiner, David B., Keshavarzian, Ali, Landay, Alan, Abdel-Mohsen, Mohamed
Format: Journal Article
Language:English
Published: United States American Society for Microbiology 20.04.2021
Subjects:
Antibodies
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Antibodies, Viral - immunology
Antibody Specificity
Antibody-Dependent Cell Cytotoxicity
Antibody-dependent cell-mediated cytotoxicity
Antigens
Biomarkers - blood
Case-Control Studies
Cohort Studies
Complement Activation
Coronaviruses
COVID-19
COVID-19 - etiology
COVID-19 - immunology
COVID-19 - virology
Cytokines
Cytotoxicity
Fc receptors
Female
Hospitalization
Humans
Immune clearance
Immunity, Innate
Immunoglobulin Fc Fragments - immunology
Inflammation
Inflammation - blood
Inflammation - etiology
Inflammation - immunology
Kruskal-Wallis test
Male
Mann-Whitney U test
Middle Aged
Observation
Pandemics
Pathogenesis
Phagocytosis
Receptors, Fc - immunology
SARS-CoV-2 - immunology
Severe acute respiratory syndrome coronavirus 2
Severity of Illness Index
Spike Glycoprotein, Coronavirus - immunology
Statistical analysis
Vaccines
COVID-19
Fc-mediated functions
SARS-CoV-2
antibody
inflammation
ISSN:2150-7511, 2161-2129, 2150-7511
Online Access:Get full text
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Summary: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. 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.
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ISSN:2150-7511
2161-2129
2150-7511
DOI:10.1128/mBio.00281-21