Seroprevalence of anti-SARS-CoV-2 antibodies in a cohort of New York City metro blood donors using multiple SARS-CoV-2 serological assays: Implications for controlling the epidemic and “Reopening”

  1. Daniel K. Jin
  2. Daniel J. Nesbitt
  3. Jenny Yang
  4. Haidee Chen
  5. Julie Horowitz
  6. Marcus Jones
  7. Rianna Vandergaast
  8. Timothy Carey
  9. Samantha Reiter
  10. Stephen J. Russell
  11. Christos Kyratsous
  12. Andrea Hooper
  13. Jennifer Hamilton
  14. Manuel Ferreira
  15. Sarah Deng
  16. Donna Straus
  17. Aris Baras
  18. Christopher D. Hillyer
  19. Larry L. Luchsinger

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Abstract

Projections of the stage of the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic and local, regional and national public health policies to limit coronavirus spread as well as “reopen” cities and states, are best informed by serum neutralizing antibody titers measured by reproducible, high throughput, and statically credible antibody (Ab) assays. To date, a myriad of Ab tests, both available and FDA authorized for emergency, has led to confusion rather than insight per se. The present study reports the results of a rapid, point-in-time 1,000-person cohort study using serial blood donors in the New York City metropolitan area (NYC) using multiple serological tests, including enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). These were then tested and associated with assays for neutralizing Ab (NAb). Of the 1,000 NYC blood donor samples in late June and early July 2020, 12.1% and 10.9% were seropositive using the Ortho Total Ig and the Abbott IgG HTSA assays, respectively. These serological assays correlated with neutralization activity specific to SARS-CoV-2. The data reported herein suggest that seroconversion in this population occurred in approximately 1 in 8 blood donors from the beginning of the pandemic in NYC (considered March 1, 2020). These findings deviate with an earlier seroprevalence study in NYC showing 13.7% positivity. Collectively however, these data demonstrate that a low number of individuals have serologic evidence of infection during this “first wave” and suggest that the notion of “herd immunity” at rates of ~60% or higher are not near. Furthermore, the data presented herein show that the nature of the Ab-based immunity is not invariably associated with the development of NAb. While the blood donor population may not mimic precisely the NYC population as a whole, rapid assessment of seroprevalence in this cohort and serial reassessment could aid public health decision making.

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  1. Version published to 10.1371/journal.pone.0250319
  2. ScreenIT

    SciScore for 10.1101/2020.11.06.20220087: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The virus neutralizing titer was determined as the reciprocal of the highest dilution at which the sample was still positive for neutralization based on assay performance relative to a pre-defined calibrator consisting of monoclonal anti-spike antibody.
    anti-spike
    suggested: None
    In-house SARS-Cov2 Binding-Antibody ELISAs: Flat-well, nickel-coated 96 well ELISA plates (Thermo Scientific; USA) were coated with 2 ug/mL of recombinant S1 spike protein, nucleocapsid protein, or Receptor Binding Domain (RBD) spike protein specific to SARS-CoV-2 in resuspension buffer (1% Human Serum Albumin in 0.01% TBST) and incubated in a stationary humidified chamber overnight at 4°C.
    S1 spike protein, nucleocapsid protein, or Receptor Binding Domain (RBD
    suggested: None
    Standard curves for both S1 and RBD assays were generated by using mouse anti-SARS-CoV-2 spike protein monoclonal antibody (clone [3A2], ABIN2452119, Antibodies-Online) as the standard.
    anti-SARS-CoV-2 spike protein
    suggested: None
    Anti-SARS-CoV-2 Nucleocapsid mouse monoclonal antibody (clone [7E1B], bsm-41414M, Bioss Antibodies) was used as a standard for nucleocapsid binding assays.
    Anti-SARS-CoV-2
    suggested: None
    Plates were then washed three times with TBST and incubated for 1 hr with ELISA assay buffer containing Goat anti-Human IgA, IgG, IgM (Heavy & Light Chain) Antibody-HRP (Cat. No. ABIN100792, Antibodies-Online) and Goat anti-Mouse IgG2b (Heavy Chain) Antibody-HRP (Cat. No. ABIN376251, Antibodies-Online) at 1:30000 and 1:3000 dilutions, respectively.
    anti-Human IgA, IgG
    suggested: None
    Antibody-HRP
    suggested: (Antibodies-Online Cat# ABIN100792, RRID:AB_10763270)
    Antibodies-Online
    suggested: (Antibodies-Online Cat# ABIN376251, RRID:AB_10763156)
    anti-Mouse IgG2b
    suggested: (Antibodies-Online Cat# ABIN376251, RRID:AB_10763156)
    Software and Algorithms
    SentencesResources
    Samples were analyzed using the Abbott SARS-CoV-2 IgG chemiluminescent microparticle immunoassay using the Abbott Architect i2000SR (Abbott Core Laboratories), as well as the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Test using the VITROS 5600 (Ortho Clinical Diagnostics).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    Standard curves were constructed in Prism 8.4 (Graphpad Software Inc.) using a Sigmoidal 4PL Non-Linear Regression (curve fit) model.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    Graphpad
    suggested: (GraphPad, RRID:SCR_000306)

    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:
    However, we recognize the limitations of the current study include a lack of generalizability as a consequence of the modestly skewed demographics of blood donors and the general population as a whole, and that this may impact the conclusions of the results. In fact, seroprevalence has been suggested to be higher in specific racial/ethnic communities based on recent studies.(15) Thus, more inclusive and complete seroprevalence studies will need to be performed in the future. Nonetheless, the authors believe that using blood donor in serial studies is an important, if indirect, measure of community immunity. In this study, we found the Ortho Total Ig and Abbott IgG HTSA assays estimate a ∼10.9-12.2% SARS-CoV-2 seroprevalence in July of 2020 in the NYC Metro area. Moreover, we found that ELISA assays, which are the gold-standard of serological quantification, corresponded with seropositive classification of donors as detected by HTSAs, thus validating the use of ELISAs in population studies. Further, in seropositive blood donors we observed a wide range of anti-SARS-CoV-2-neutralizing activity that was skewed towards low to moderate NT100 titers. This trend is in agreement with our previous investigation of convalescent plasma donors(16) and a study of patients recovering from COVID-19, both of which also showed large variability and modest levels of neutralizing activity in plasma units.(17) Our estimation of the NYC Metro area blood donor seroconversion is in agreement with o...

    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

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  3. Version published to 10.1101/2020.11.06.20220087v1 on medRxiv