tetano
Editor, Senior Moderator
mBio
. 2021 Apr 20;12(2):e00281-21.
doi: 10.1128/mBio.00281-21.
COVID-19 Severity Is Associated with Differential Antibody Fc-Mediated Innate Immune Functions
Opeyemi S Adeniji[SUP] 1 [/SUP], Leila B Giron[SUP] 1 [/SUP], Mansi Purwar[SUP] 1 [/SUP], Netanel F Zilberstein[SUP] 2 [/SUP], Abhijeet J Kulkarni[SUP] 1 [/SUP], Maliha W Shaikh[SUP] 2 [/SUP], Robert A Balk[SUP] 2 [/SUP], James N Moy[SUP] 2 [/SUP], Christopher B Forsyth[SUP] 2 [/SUP], Qin Liu[SUP] 1 [/SUP], Harsh Dweep[SUP] 1 [/SUP], Andrew Kossenkov[SUP] 1 [/SUP], David B Weiner[SUP] 1 [/SUP], Ali Keshavarzian[SUP] 2 [/SUP], Alan Landay[SUP] 2 [/SUP], Mohamed Abdel-Mohsen[SUP] 3 [/SUP]
Affiliations
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.
Keywords: COVID-19; Fc-mediated functions; SARS-CoV-2; antibody; inflammation.
. 2021 Apr 20;12(2):e00281-21.
doi: 10.1128/mBio.00281-21.
COVID-19 Severity Is Associated with Differential Antibody Fc-Mediated Innate Immune Functions
Opeyemi S Adeniji[SUP] 1 [/SUP], Leila B Giron[SUP] 1 [/SUP], Mansi Purwar[SUP] 1 [/SUP], Netanel F Zilberstein[SUP] 2 [/SUP], Abhijeet J Kulkarni[SUP] 1 [/SUP], Maliha W Shaikh[SUP] 2 [/SUP], Robert A Balk[SUP] 2 [/SUP], James N Moy[SUP] 2 [/SUP], Christopher B Forsyth[SUP] 2 [/SUP], Qin Liu[SUP] 1 [/SUP], Harsh Dweep[SUP] 1 [/SUP], Andrew Kossenkov[SUP] 1 [/SUP], David B Weiner[SUP] 1 [/SUP], Ali Keshavarzian[SUP] 2 [/SUP], Alan Landay[SUP] 2 [/SUP], Mohamed Abdel-Mohsen[SUP] 3 [/SUP]
Affiliations
- PMID: 33879594
- DOI: 10.1128/mBio.00281-21
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.
Keywords: COVID-19; Fc-mediated functions; SARS-CoV-2; antibody; inflammation.