COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva
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...
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| Published in | Journal of clinical microbiology Vol. 59; no. 1 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Society for Microbiology
17.12.2020
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| Subjects | |
| Online Access | Get full text |
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| 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.
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. |
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| AbstractList | 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 (
= 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. 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.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. 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. 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. 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. |
| Author | Clarke, William A. Pekosz, Andrew Sherman, Amy C. Rouphael, Nadine Betenbaugh, Michael J. Larman, H. Benjamin Pisanic, Nora Thomas, David L. Granger, Douglas A. Caturegli, Patrizio P. Fairley, Jessica K. Edupuganti, Srilatha Randad, Pranay R. Manabe, Yukari C. Laeyendecker, Oliver Klein, Sabra L. Collins, Matthew H. Heaney, Christopher D. Granger, Steve W. Kruczynski, Kate Detrick, Barbara |
| Author_xml | – sequence: 1 givenname: Nora surname: Pisanic fullname: Pisanic, Nora organization: Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 2 givenname: Pranay R. surname: Randad fullname: Randad, Pranay R. organization: Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 3 givenname: Kate surname: Kruczynski fullname: Kruczynski, Kate organization: Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 4 givenname: Yukari C. surname: Manabe fullname: Manabe, Yukari C. organization: Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 5 givenname: David L. surname: Thomas fullname: Thomas, David L. organization: Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 6 givenname: Andrew orcidid: 0000-0003-3248-1761 surname: Pekosz fullname: Pekosz, Andrew organization: Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 7 givenname: Sabra L. surname: Klein fullname: Klein, Sabra L. organization: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA, Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 8 givenname: Michael J. surname: Betenbaugh fullname: Betenbaugh, Michael J. organization: Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 9 givenname: William A. surname: Clarke fullname: Clarke, William A. organization: Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 10 givenname: Oliver surname: Laeyendecker fullname: Laeyendecker, Oliver organization: Division of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA, Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, USA – sequence: 11 givenname: Patrizio P. surname: Caturegli fullname: Caturegli, Patrizio P. organization: Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA, Division of Immunology, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 12 givenname: H. Benjamin surname: Larman fullname: Larman, H. Benjamin organization: Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA, Division of Immunology, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 13 givenname: Barbara surname: Detrick fullname: Detrick, Barbara organization: Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA, Division of Immunology, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA – sequence: 14 givenname: Jessica K. surname: Fairley fullname: Fairley, Jessica K. organization: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA – sequence: 15 givenname: Amy C. surname: Sherman fullname: Sherman, Amy C. organization: The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Decatur, Georgia, USA – sequence: 16 givenname: Nadine surname: Rouphael fullname: Rouphael, Nadine organization: The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Decatur, Georgia, USA – sequence: 17 givenname: Srilatha surname: Edupuganti fullname: Edupuganti, Srilatha organization: The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Decatur, Georgia, USA – sequence: 18 givenname: Douglas A. surname: Granger fullname: Granger, Douglas A. organization: Institute for Interdisciplinary Salivary Bioscience Research, University of California at Irvine, Irvine, California, USA – sequence: 19 givenname: Steve W. surname: Granger fullname: Granger, Steve W. organization: Salimetrics, LLC, Carlsbad, California, USA – sequence: 20 givenname: Matthew H. surname: Collins fullname: Collins, Matthew H. organization: The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Decatur, Georgia, USA – sequence: 21 givenname: Christopher D. orcidid: 0000-0003-3211-8495 surname: Heaney fullname: Heaney, Christopher D. organization: Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA, Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33067270$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Copyright © 2020 American Society for Microbiology. Copyright © 2020 American Society for Microbiology. 2020 American Society for Microbiology |
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| DocumentTitleAlternate | Saliva-Based SARS-CoV-2 Serology at Population Scale, Pisanic et al Saliva-Based SARS-CoV-2 Serology at Population Scale |
| EISSN | 1098-660X |
| Editor | Loeffelholz, Michael J |
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| Issue | 1 |
| Keywords | COVID-19 saliva SARS-CoV-2 diagnostics multiplex oral fluid serology immunoserology antibody test |
| Language | English |
| License | Copyright © 2020 American Society for Microbiology. All Rights Reserved. https://doi.org/10.1128/ASMCopyrightv2 All Rights Reserved. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Nora Pisanic and Pranay R. Randad contributed equally. Order was determined on the following basis: N.P. developed the first draft of the manuscript, led laboratory analyses, and performed data analyses; P.R.R. provided critical input on the manuscript, led laboratory analyses, and performed data analyses. Citation Pisanic N, Randad PR, Kruczynski K, Manabe YC, Thomas DL, Pekosz A, Klein SL, Betenbaugh MJ, Clarke WA, Laeyendecker O, Caturegli PP, Larman HB, Detrick B, Fairley JK, Sherman AC, Rouphael N, Edupuganti S, Granger DA, Granger SW, Collins MH, Heaney CD. 2021. COVID-19 serology at population scale: SARS-CoV-2-specific antibody responses in saliva. J Clin Microbiol 59:e02204-20. https://doi.org/10.1128/JCM.02204-20. |
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| PublicationTitle | Journal of clinical microbiology |
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| Snippet | 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... |
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| Title | COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva |
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