Longitudinal humoral antibody response to SARS-CoV-2 infection among healthcare workers in a New York City hospital

  1. Vidya Menon
  2. Masood A Shariff
  3. Victor Perez Gutierrez
  4. Juan M Carreño
  5. Bo Yu
  6. Muzamil Jawed
  7. Marcia Gossai
  8. Elisenda Valdez
  9. Anjana Pillai
  10. Usha Venugopal
  11. Moiz Kasubhai
  12. Vihren Dimitrov
  13. Florian Krammer

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Abstract

Dynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggest an initial decay of antibody followed by subsequent stabilisation. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCWs).

Design

A prospective longitudinal study.

Setting

This study was conducted in a New York City public hospital in the South Bronx, New York.

Participants

HCWs participated in phase 1 (N=500) and were followed up 4 months later in phase 2 (N=178) of the study. They underwent SARS-CoV-2 PCR and serology testing for N and S protein antibodies, in addition to completion of an online survey in both phases. Analysis was performed on the 178 participants who participated in both phases of the study.

Primary outcome measure

Evaluate longitudinal humoral responses to viral N (qualitative serology testing) and S protein (quantitative Mount Sinai Health System ELISA to detect receptor-binding domain and full-length S reactive antibodies) by measuring rate of decay.

Results

Anti-N antibody positivity was 27% and anti-S positivity was 28% in phase 1. In phase 1, anti-S titres were higher in symptomatic (6754 (5177–8812)) than in asymptomatic positive subjects (5803 (2825–11 920)). Marginally higher titres (2382 (1494–3797)) were seen in asymptomatic compared with the symptomatic positive subgroup (2198 (1753–2755)) in phase 2. A positive correlation was noted between age (R=0.269, p<0.01), number (R=0.310, p<0.01) and duration of symptoms (R=0.434, p<0.01), and phase 1 anti-S antibody titre. A strong correlation (R=0.898, p<0.001) was observed between phase 1 titres and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever (R=0.428, p<0.001), gastrointestinal symptoms (R=0.340, p<0.05), and total number (R=0.357, p<0.01) and duration of COVID-19 symptoms (R=0.469, p<0.001).

Conclusions

Higher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as a faster decay between the two time points.

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  1. Version published to 10.1136/bmjopen-2021-051045
  2. ScreenIT

    SciScore for 10.1101/2021.03.02.21252362: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Study setting and population: The study was a cross sectional cohort study done in two phases after receiving Institutional Review Board approval (IRB # 20-009, Lincoln Medical Center, Office of the Institutional Review Board approved as per 45 CFR 46 & 21 CFR50,56 under a full board committee and gave its approval on 4/28/2020).
    Consent: In the Phase 1 of the study, after informed consent, participants underwent qualitative serology testing (Abbott Architect SARS-CoV-2 IgG Assay, Abbott Park, IL 60064 USA)25 and a nasopharyngeal swab for SARS-CoV-2 (Bio-Reference Laboratories, Inc., Elmwood Park, NJ, USA).
    Randomizationnot detected.
    BlindingSurvey: The online survey was accessed by a unique identification number assigned to each participant, blinded to the research team to ensure confidentiality.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Multiple linear regression was applied to determine the predictors of log10 rate of decay from Phase 1 to Phase 2 of anti-spike antibodies.
    anti-spike
    suggested: None
    Software and Algorithms
    SentencesResources
    In the Phase 1 of the study, after informed consent, participants underwent qualitative serology testing (Abbott Architect SARS-CoV-2 IgG Assay, Abbott Park, IL 60064 USA)25 and a nasopharyngeal swab for SARS-CoV-2 (Bio-Reference Laboratories, Inc., Elmwood Park, NJ, USA).
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    Participants from Phase 1 who agreed to return for follow up serology testing (Abbott and MSH ELISA) and completion of a follow-up online survey were part of Phase 2 of the study.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    All statistical analyses were performed using SPSS version 27 (IBM, USA).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    Our study has the following limitations: First being a single center study with a small convenience sampling that included a smaller number of participants in Phase 2 of the study. Following the pandemic, the HCWs who volunteered from around the country were transferred back and lost to follow-up, which did decrease the overall sample size, but the rates of positive and negative results remained proportional. Second, the likelihood of a recall bias in the participant’s responses on the online survey may exist. Lastly, as a cross-sectional seroprevalence study the findings can underestimate rates of prior infections based on timing of the testing given that antibodies are only transiently detectable following infection. In conclusion, findings from this study are similar to other studies that have reported that higher magnitude of anti-spike titres may correlate with protection against reinfection, in spite of the observed decay in the antibody levels20,21. Nevertheless, further studies to evaluate the longevity of immunity, especially in context of widespread administration of spike-based vaccine among HCWs would be important in predicting herd immunity to COVID-19 infections.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    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 10.1101/2021.03.02.21252362v1 on medRxiv