Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies

Cell Rep Med. 2021 May 18;2(5):100275. doi: 10.1016/j.xcrm.2021.100275. Epub 2021 Apr 20.


Many SARS-CoV-2-infected individuals remain asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mildly symptomatic, and 21 hospitalized patients with COVID-19. We measure anti-spike immunoglobulin G (IgG), IgA, and IgM levels with the S-Flow assay and map IgG-targeted epitopes with a Luminex assay. We also evaluate neutralization, complement deposition, and antibody-dependent cellular cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC, and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than they are in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.

Keywords: ADCC; SARS-CoV-2; antibody; asymptomatic; complement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Antibodies, Viral / immunology
  • Antibody-Dependent Cell Cytotoxicity
  • Antigen-Antibody Reactions
  • Asymptomatic Diseases
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Complement System Proteins / metabolism
  • Epitopes / immunology
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Neutralization Tests
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / immunology*
  • Young Adult


  • Antibodies, Viral
  • Epitopes
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Complement System Proteins