COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva

J Clin Microbiol. 2020 Dec 17;59(1):e02204-20. doi: 10.1128/JCM.02204-20. Print 2020 Dec 17.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (n = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.

Keywords: COVID-19; SARS-CoV-2; antibody test; diagnostics; immunoserology; multiplex; oral fluid; saliva; serology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Antibodies, Viral / analysis*
  • Antibodies, Viral / blood*
  • COVID-19 / diagnosis*
  • COVID-19 Nucleic Acid Testing / methods
  • Coronavirus Nucleocapsid Proteins / immunology
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Male
  • SARS-CoV-2 / immunology*
  • Saliva / immunology*
  • Spike Glycoprotein, Coronavirus / immunology


  • Antibodies, Viral
  • Coronavirus Nucleocapsid Proteins
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • N protein, SARS-CoV
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2