SARS-CoV-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild COVID-19 infection

PLoS One. 2022 Jan 12;17(1):e0262169. doi: 10.1371/journal.pone.0262169. eCollection 2022.


Current SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1965 healthcare workers, of which 381 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in most participants, 96%, at least four months post infection, despite having had no or mild symptoms. Virus neutralization capacity was confirmed by microneutralization assay in 91% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 80% of previously anti-nucleocapsid IgG positive healthcare workers. Both anti-spike and anti-nucleocapsid IgG levels were significantly higher in previously hospitalized COVID-19 patients four months post infection than in healthcare workers four months post infection (p = 2*10-23 and 2*10-13 respectively). Although the magnitude of humoral response was associated with disease severity, our findings support a durable and functional humoral response after SARS-CoV-2 infection even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Asymptomatic Infections / epidemiology
  • COVID-19 / immunology
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Female
  • Health Personnel
  • Humans
  • Immunity, Humoral*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Nucleocapsid / immunology
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

This study was funded by Region Stockholm (CT, SoH), Knut and Alice Wallenberg foundation (CT, SoH), Jonas & Christina af Jochnick foundation (CT), Lundblad family foundation (CT), Science for Life Laboratory (PN), Erling-Persson family foundation (SoH), Svenska Sällskapet för Medicinsk Forskning (SM), and Swedish Research Council (JK), CIMED (JK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.