Covid-19 severity is associated with differential antibody fc-mediated innate immune functions

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

Research output: Contribution to journalArticlepeer-review


Beyond neutralization, antibodies binding to their Fc receptors elicit several innate immune functions including antibody-dependent complement deposi-tion (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.

Original languageEnglish (US)
Article numbere00281-21
Issue number2
StatePublished - 2021
Externally publishedYes


  • Antibody
  • COVID-19
  • Fc-mediated functions
  • Inflammation
  • SARS-CoV-2

ASJC Scopus subject areas

  • Microbiology
  • Virology


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