Asymptomatic COVID-19: disease tolerance with efficient anti-viral immunity against SARS-CoV-2

EMBO Mol Med. 2021 Jun 7;13(6):e14045. doi: 10.15252/emmm.202114045. Epub 2021 May 27.

Abstract

The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS-CoV-2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies, and cellular immune phenotypes of asymptomatic patients with acute SARS-CoV-2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro-inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro-inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus-specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS-CoV-2 was observed in asymptomatic patients. In addition, asymptomatic COVID-19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro-inflammatory and more protective immune responses against SARS-CoV-2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID-19.

Keywords: COVID-19; SARS-CoV-2; asymptomatic; disease tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • COVID-19 / immunology
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Carrier State / immunology*
  • Carrier State / pathology
  • Carrier State / virology
  • Cytokines / metabolism
  • Humans
  • Monocytes / cytology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Neutrophils / cytology
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • SARS-CoV-2 / isolation & purification
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Transcriptome
  • Up-Regulation
  • Vascular Endothelial Growth Factor D / metabolism

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Vascular Endothelial Growth Factor D