COVID-19 serology at population scale: SARS-CoV-2-specific antibody responses in saliva

Pranay R Randad; Nora Pisanic; Kate Kruczynski; Yukari C Manabe; David 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 Collins; Christopher D Heaney

doi:10.1101/2020.05.24.20112300

COVID-19 serology at population scale: SARS-CoV-2-specific antibody responses in saliva

medRxiv [Preprint]. 2020 May 26:2020.05.24.20112300. doi: 10.1101/2020.05.24.20112300.

Authors

Pranay R Randad¹, Nora Pisanic¹, Kate Kruczynski¹, Yukari C Manabe^{2

3}, David Thomas², Andrew Pekosz^{1

4}, Sabra L Klein^{4

5}, Michael J Betenbaugh⁶, William A Clarke³, Oliver Laeyendecker^{2

7

8}, Patrizio P Caturegli^{3

9}, H Benjamin Larman^{3

9}, Barbara Detrick^{3

9}, Jessica K Fairley¹⁰, Amy C Sherman¹¹, Nadine Rouphael¹¹, Srilatha Edupuganti¹¹, Douglas A Granger¹², Steve W Granger¹³, Matthew Collins¹¹, Christopher D Heaney^{1

6

14}

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 Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
⁷ Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
⁸ Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, USA.
⁹ Division of Immunology, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁰ Hubert Department of Global Health, Emory University Rollins School of Public Health, Atlanta, GA, USA.
¹¹ The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Decatur, Georgia, USA.
¹² Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, California, USA.
¹³ Salimetrics, LLC, Carlsbad, California, USA.
¹⁴ Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.

Abstract

Non-invasive SARS-CoV-2 antibody testing is urgently needed to estimate the incidence and prevalence of SARS-CoV-2 infection at the general population level. Precise knowledge of population immunity could allow government bodies to make informed decisions about how and when to relax stay-at-home directives and to reopen the economy. We hypothesized that salivary antibodies to SARS-CoV-2 could serve as a non-invasive alternative to serological testing for widespread monitoring of SARS-CoV-2 infection throughout the population. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology and tested 167 saliva and 324 serum samples, including 134 and 118 negative saliva and serum samples, respectively, collected before the COVID-19 pandemic, and 33 saliva and 206 serum samples from participants with RT-PCR-confirmed SARS-CoV-2 infection. We evaluated the correlation of results obtained in saliva vs. serum and determined the sensitivity and specificity for each diagnostic media, stratified by antibody isotype, for detection of SARS-CoV-2 infection based on COVID-19 case designation for all specimens. Matched serum and saliva SARS-CoV-2 antigen-specific IgG responses were significantly correlated. Within the 10-plex SARS-CoV-2 panel, the salivary anti-nucleocapsid (N) protein IgG response resulted in the highest sensitivity for detecting prior SARS-CoV-2 infection (100% sensitivity at ≥10 days post-SARS-CoV-2 symptom onset). The salivary anti-receptor binding domain (RBD) IgG response resulted in 100% specificity. Among individuals with SARS-CoV-2 infection confirmed with RT-PCR, the temporal kinetics of IgG, IgA, and IgM in saliva were consistent with those observed in serum. SARS-CoV-2 appears to trigger a humoral immune response resulting in the almost simultaneous rise of IgG, IgM and IgA levels both in serum and in saliva, mirroring responses consistent with the stimulation of existing, cross-reactive B cells. SARS-CoV-2 antibody testing in saliva can play a critically important role in large-scale "sero"-surveillance to address key public health priorities and guide policy and decision-making for COVID-19.

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

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Preprint

Abstract

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