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

Abstract
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.
AuthorsNora Pisanic, Pranay R Randad, Kate Kruczynski, Yukari C Manabe, David L Thomas, Andrew Pekosz, Sabra L Klein, Michael J Betenbaugh, William A Clarke, Oliver Laeyendecker, Patrizio P Caturegli, H Benjamin Larman, Barbara Detrick, Jessica K Fairley, Amy C Sherman, Nadine Rouphael, Srilatha Edupuganti, Douglas A Granger, Steve W Granger, Matthew H Collins, Christopher D Heaney
JournalJournal of clinical microbiology (J Clin Microbiol) Vol. 59 Issue 1 (12 17 2020) ISSN: 1098-660X [Electronic] United States
PMID33067270 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
CopyrightCopyright © 2020 American Society for Microbiology.
Chemical References
  • Antibodies, Viral
  • Coronavirus Nucleocapsid Proteins
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • N protein, SARS-CoV
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
Topics
  • Antibodies, Viral (analysis, 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)

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