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

Nora 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

doi:10.1128/JCM.02204-20

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.

Authors

Nora Pisanic^#¹, Pranay R Randad^#¹, Kate Kruczynski¹, Yukari C Manabe^{2

3}, David L Thomas², Andrew Pekosz^{1

4}, Sabra L Klein^{4

5

6}, Michael J Betenbaugh⁷, William A Clarke³, Oliver Laeyendecker^{2

8

9}, Patrizio P Caturegli^{3

10}, H Benjamin Larman^{3

10}, Barbara Detrick^{3

10}, Jessica K Fairley¹¹, Amy C Sherman¹², Nadine Rouphael¹², Srilatha Edupuganti¹², Douglas A Granger¹³, Steve W Granger¹⁴, Matthew H Collins¹², Christopher D Heaney^{15

6

8}

Affiliations

¹ Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
² Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
³ Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
⁴ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
⁵ Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
⁶ Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
⁷ Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
⁸ Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
⁹ Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, USA.
¹⁰ Division of Immunology, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
¹¹ Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
¹² The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Decatur, Georgia, USA.
¹³ Institute for Interdisciplinary Salivary Bioscience Research, University of California at Irvine, Irvine, California, USA.
¹⁴ Salimetrics, LLC, Carlsbad, California, USA.
¹⁵ Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA cheaney1@jhu.edu.

^# Contributed equally.

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.

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

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding