Evidence map›Paper›PMID 36773929›Full record

ArticleJournal of immunological methods2023

Methodological approaches to optimize multiplex oral fluid SARS-CoV-2 IgG assay performance and correlation with serologic and neutralizing antibody responses.

Nora Pisanic, Annukka A R Antar, Kate L Kruczynski, Magdielis Gregory Rivera, Santosh Dhakal, Kristoffer Spicer, Pranay R Randad, Andrew Pekosz, Sabra L Klein, Michael J Betenbaugh and 5 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of immunological methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Nora PisanicDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. Electronic address: npisani1@jhu.edu.
Annukka A R AntarDivision of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Kate L KruczynskiDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Magdielis Gregory RiveraDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Santosh DhakalDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Kristoffer SpicerDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Pranay R RandadDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Andrew PekoszDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Sabra L KleinDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Michael J BetenbaughDepartment of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA.
Barbara DetrickDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
William ClarkeDepartment of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
David L ThomasDivision of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Yukari C ManabeDivision of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Christopher D HeaneyDepartment of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. Electronic address: cheaney1@jhu.edu.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

ECHODAC (Environmental Influences on Child Health Outcomes Data Analysis Center)U24OD023382 · OD · JOHNS HOPKINS UNIVERSITY · PI Diane J Catellier, LISA P JACOBSON · 2016 to 2026
$148.4M
The Center for Advancing Point of Care in Heart, Lung, Blood and Sleep DiseasesU54HL143541 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BRYAN O BUCHHOLZ, Nathaniel Scott Hafer · 2018 to 2026
$141.0M
LC: HIV Prevention Trials Network - Laboratory Support for the SARS-CoV-2 Seroprevalence Study (CoVPN 5002)UM1AI068613 · NIAID · JOHNS HOPKINS UNIVERSITY · PI SUSAN H ESHLEMAN, Mark A Marzinke · 2011 to 2026
$100.2M
TrainingU54EB007958 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI Susan Anne Tuddenham · 2007 to 2026
$34.6M
Virology Resource CoreU54CA260492 · NCI · JOHNS HOPKINS UNIVERSITY · PI KLEIN, SABRA L. · 2020 to 2024
$10.4M
Antimicrobial resistant E. coli before and after California Senate bill 27 (ARES): a natural experimentR01AI130066 · NIAID · KAISER FOUNDATION RESEARCH INSTITUTE · PI TARTOF, SARA · 2017 to 2021
$3.8M
Arsenic and immune response to influenza vaccination in pregnant women and newbornsR01ES026973 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI HEANEY, CHRISTOPHER D, LABRIQUE, ALAIN BERNARD · 2017 to 2021
$3.6M
The HIV Latent Reservoir, Suboptimal Immune Response on Antiretroviral Therapy, and Exogenous Cytokine TherapiesK08AI143391 · NIAID · JOHNS HOPKINS UNIVERSITY · PI ANTAR, ANNUKKA AIDA ROSE · 2019 to 2023
$994k
Multiplex oral fluid antibody assay for arbovirus diagnosis, surveillance and preventionR21AI139784 · NIAID · JOHNS HOPKINS UNIVERSITY · PI COLLINS, MATTHEW, HEANEY, CHRISTOPHER D · 2018 to 2019
$459k
Development of a point of care lateral flow diagnostic to test for acute and past hepatitis E (HEV) in salivaR43AI141265 · NIAID · NANOCOMPOSIX, INC. · PI BALDWIN, RICHARD KIMO, PISANIC, NORA · 2018 to 2018
$225k
NCI NIH HHS U54 CA260492NHLBI NIH HHS U54 HL143541NIAID NIH HHS K08 AI143391NIAID NIH HHS R01 AI130066NIAID NIH HHS R21 AI139784NIAID NIH HHS R43 AI141265NIAID NIH HHS UM1 AI068613NIBIB NIH HHS U54 EB007958NIEHS NIH HHS R01 ES026973NIH HHS U24 OD023382
6 · The paper itself

Abstract

backgroundOral fluid (hereafter, saliva) is a non-invasive and attractive alternative to blood for SARS-CoV-2 IgG testing; however, the heterogeneity of saliva as a matrix poses challenges for immunoassay performance.

objectivesTo optimize performance of a magnetic microparticle-based multiplex immunoassay (MIA) for SARS-CoV-2 IgG measurement in saliva, with consideration of: i) threshold setting and validation across different MIA bead batches; ii) sample qualification based on salivary total IgG concentration; iii) calibration to U.S. SARS-CoV-2 serological standard binding antibody units (BAU); and iv) correlations with blood-based SARS-CoV-2 serological and neutralizing antibody (nAb) assays.

methodsThe salivary SARS-CoV-2 IgG MIA included 2 nucleocapsid (N), 3 receptor-binding domain (RBD), and 2 spike protein (S) antigens. Gingival crevicular fluid (GCF) swab saliva samples were collected before December 2019 (n = 555) and after molecular test-confirmed SARS-CoV-2 infection from 113 individuals (providing up to 5 repeated-measures; n = 398) and used to optimize and validate MIA performance (total n = 953). Combinations of IgG responses to N, RBD and S and total salivary IgG concentration (μg/mL) as a qualifier of nonreactive samples were optimized and validated, calibrated to the U.S. SARS-CoV-2 serological standard, and correlated with blood-based SARS-CoV-2 IgG ELISA and nAb assays.

resultsThe sum of signal to cutoff (S/Co) to all seven MIA SARS-CoV-2 antigens and disqualification of nonreactive saliva samples with ≤15 μg/mL total IgG led to correct classification of 62/62 positives (sensitivity [Se] = 100.0%; 95% confidence interval [CI] = 94.8%, 100.0%) and 108/109 negatives (specificity [Sp] = 99.1%; 95% CI = 97.3%, 100.0%) at 8-million beads coupling scale and 80/81 positives (Se = 98.8%; 95% CI = 93.3%, 100.0%] and 127/127 negatives (Sp = 100%; 95% CI = 97.1%, 100.0%) at 20-million beads coupling scale. Salivary SARS-CoV-2 IgG crossed the MIA cutoff of 0.1 BAU/mL on average 9 days post-COVID-19 symptom onset and peaked around day 30. Among n = 30 matched saliva and plasma samples, salivary SARS-CoV-2 MIA IgG levels correlated with corresponding-antigen plasma ELISA IgG (N: ρ = 0.76, RBD: ρ = 0.83, S: ρ = 0.82; all p < 0.001). Correlations of plasma SARS-CoV-2 nAb assay area under the curve (AUC) with salivary MIA IgG (N: ρ = 0.68, RBD: ρ = 0.78, S: ρ = 0.79; all p < 0.001) and with plasma ELISA IgG (N: ρ = 0.76, RBD: ρ = 0.79, S: ρ = 0.76; p < 0.001) were similar.

conclusionsA salivary SARS-CoV-2 IgG MIA produced consistently high Se (> 98.8%) and Sp (> 99.1%) across two bead coupling scales and correlations with nAb responses that were similar to blood-based SARS-CoV-2 IgG ELISA data. This non-invasive salivary SARS-CoV-2 IgG MIA could increase engagement of vulnerable populations and improve broad understanding of humoral immunity (kinetics and gaps) within the evolving context of booster vaccination, viral variants and waning immunity.

Indexed as

Blood Group AntigensCOVID-19Antibodies, NeutralizingAntibodies, ViralCOVID-19 TestingHumansImmunoglobulin GSARS-CoV-2Antibodies, NeutralizingAntibodies, ViralBlood Group AntigensImmunoglobulin GAntibody kineticsCOVID-19Multiplex assayOral fluidSalivaSARS-CoV-2SeroprevalenceSerosurveillance

Identifiers

PMID36773929
PMCPMC9911157
OpenAlexW4319659323

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.