Duration of SARS-CoV-2 sero-positivity in a large longitudinal sero-surveillance cohort: the COVID-19 Community Research Partnership

  1. The COVID-19 Community Research Partnership Study Group
  2. David M. Herrington
  3. John W. Sanders
  4. Thomas F. Wierzba
  5. Martha Alexander-Miller
  6. Mark Espeland
  7. Alain G. Bertoni
  8. Allison Mathews
  9. Austin L. Seals
  10. Iqra Munawar
  11. Michael S. Runyon
  12. Lewis H. McCurdy
  13. Michael A. Gibbs
  14. Karen Kotloff
  15. DeAnna Friedman-Klabanoff
  16. William Weintraub
  17. Adolfo Correa
  18. Diane Uschner
  19. Sharon Edelstein
  20. Michele Santacatterina

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Abstract

Background

Estimating population prevalence and incidence of prior SARS-CoV-2 infection is essential to formulate public health recommendations concerning the COVID-19 pandemic. However, interpreting estimates based on sero-surveillance requires an understanding of the duration of elevated antibodies following SARS-CoV-2 infection, especially in the large number of people with pauci-symptomatic or asymptomatic disease.

Methods

We examined > 30,000 serology assays for SARS-CoV-2 specific IgG and IgM assays acquired longitudinally in 11,468 adults between April and November 2020 in the COVID-19 Community Research Partnership.

Results

Among participants with serologic evidence for infection but few or no symptoms or clinical disease, roughly 50% sero-reverted in 30 days of their initial positive test. Sero-reversion occurred more quickly for IgM than IgG and for antibodies targeting nucleocapsid protein compared with spike proteins, but was not associated with age, sex, race/ethnicity, or healthcare worker status.

Conclusions

The short duration of antibody response suggests that the true population prevalence of prior SARS-CoV-2 infection may be significantly higher than presumed based on earlier sero-surveillance studies. The impact of the large number of minimally symptomatic COVID-19 cases with only a brief antibody response on population immunity remains to be determined.

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  1. Version published to 10.1186/s12879-021-06517-6
  2. ScreenIT

    SciScore for 10.1101/2021.01.27.21250615: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: After providing informed consent, participants were asked to record daily symptoms (e.g., fever, cough, shortness of breath, etc.) related to COVID-1911 using a web-based Patient Monitoring System application (Oracle Corporation, Redwood Shores, California).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    lateral flow assay (LFA) to test for IgM and IgG antibodies to the SARS-CoV-2 nucleocapsid antigens (n=13,752 assays).
    IgG
    suggested: None
    SARS-CoV-2 nucleocapsid antigens
    suggested: None
    Both assays were validated at the Frederick National Laboratory for Cancer Research (FNLCR) by the National Cancer Institute (NCI) using a panel of antibody-positive samples from patients with PCR confirmed SARS-CoV-2 infection or pre-pandemic controls (Panel 2); Syntron: (antibody: sensitivity/specificity); IgM: 93.3%/97.5%; IgG:73.3%/100%; IgM or IgG:96.7%/97.5%), Innovita: (antibody: sensitivity/specificity); IgM:93.3%/98.8%; IgG: 93.3%/98.8%; IgM or IgG:100%/97.5%.
    IgM
    suggested: None
    Software and Algorithms
    SentencesResources
    Logistic regression was used to estimate the relative odds of seroconversion as a function of symptom prevalence (JMP Ver. 15.0, SAS Institute).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are several limitations of our study. First, the sampling frame (two large healthcare system patient populations) and participants (volunteers) may reflect various biases including response bias that could influence rates of sero-conversion and sero-reversion in unknown directions. The preponderance of white participants and more female than male participants in the current study also raises questions about the generalizability of the results, although within the limits of statistical power afforded by the sample size, there were no clear difference in rates of sero-reversion by age, race/ethnicity or sex. The serology tests employed in this study were qualitative lateral flow assays. Although validated with convalescent samples in people with significantly elevated antibody titers, the calibration and comparison of these assays as a function of independently quantified antibody titers is not known. Some false positives and false negatives are likely. However, if we assume the test characteristics remained constant over time, and consider the consistency between the simple binomial rates and those estimated using interval censored repeated measures, we believe the observed change in rates of sero-positivity are reasonable estimates of the duration of detectable antibody responses in a population. The study design and contemporary factors related to the pandemic did not permit a regularly scheduled cadence of testing. Nevertheless, the data include a large number of test...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.01.27.21250615v1 on medRxiv