SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

EBioMedicine. 2021 Jun;68:103410. doi: 10.1016/j.ebiom.2021.103410. Epub 2021 Jun 4.


Background: The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search and evaluation of new treatment modalities and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed.

Methods: We included 203 recovered SARS-CoV-2 infected patients in Denmark between April 3rd and July 9th 2020, at least 14 days after COVID-19 symptom recovery. The participants had experienced a range of disease severities from asymptomatic to severe. We collected plasma, serum and PBMC's for analysis of SARS-CoV-2 specific antibody response by Meso Scale analysis including other coronavirus strains, ACE2 competition, IgA ELISA, pseudovirus neutralization capacity, and dextramer flow cytometry analysis of CD8+ T cells. The immunological outcomes were compared amongst severity groups within the cohort, and 10 pre-pandemic SARS-CoV-2 negative controls.

Findings: We report broad serological profiles within the cohort, detecting antibody binding to other human coronaviruses. 202(>99%) participants had SARS-CoV-2 specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 193(95%) individuals. A significant positive correlation (r=0.7804) between spike-ACE2 blocking antibody titers and neutralization potency was observed. Further, SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 95 of 106(90%) HLA-A2+ individuals.

Interpretation: The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+ T-cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of their disease severity.

Funding: This study was supported by the Danish Ministry for Research and Education (grant# 0238-00001B) and The Danish Innovation Fund (grant# 0208-00018B).

Keywords: Adaptive; Antibody; Asymptomatic; CD8(+) T-cell; COVID-19; Corona; Immune response; SARS-CoV-2; Severe; Virus.

MeSH terms

  • Adaptive Immunity
  • Adult
  • Aged
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Animals
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood
  • CD8-Positive T-Lymphocytes / metabolism
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Cell Line
  • Denmark
  • Female
  • Humans
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / immunology*
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2