Correlation between SARS‐COV‐2 antibody screening by immunoassay and neutralizing antibody testing

  1. Alfredo Mendrone‐Junior
  2. Carla Luana Dinardo
  3. Suzete Cleuza Ferreira
  4. Anna Nishya
  5. Nanci Alves Salles
  6. Cesar de Almeida Neto
  7. Debora Toshei Hamasaki
  8. Tila Facincani
  9. Lucas Bassolli de Oliveira Alves
  10. Rafael Rahal Guaragna Machado
  11. Danielle Bastos Araujo
  12. Edison Luiz Durigon
  13. Vanderson Rocha
  14. Ester Cerdeira Sabino

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Abstract

Background

The efficacy of convalescent plasma (CP), an alternative for the treatment of COVID‐19, depends on high titers of neutralizing antibodies (nAbs), but assays for quantifying nAbs are not widely available. Our goal was to develop a strategy to predict high titers of nAbs based on the results of anti‐SARS‐CoV‐2 immunoassays and the clinical characteristics of CP donors.

Study Design and Methods

A total of 214 CP donors were enrolled and tested for the presence of anti‐SARS‐CoV‐2 antibodies (IgG) using two commercial immunoassays: EUROIMMUN (ELISA) and Abbott (Chemiluminescence). Quantification of nAbs was performed using the Cytopathic Effect‐based Virus Neutralization test. Three criteria for identifying donors with nAbs ≥ 1:160 were tested: – C1: Curve ROC; − C2: Conditional decision tree considering only the IA results and – C3: Conditional decision tree including both the IA results and the clinical variables.

Results

The performance of the immunoassays was similar referring to both S/CO and predictive value for identifying nAbs titers ≥1:160. Regarding the studied criteria for identifying CP donors with high nAbs titers: (a) C1 showed 76.1% accuracy if S/CO = 4.65, (b) C2 presented 76.1% accuracy if S/CO ≥4.57 and (c) C3 had 71.6% accuracy if S/CO was ≥4.57 or if S/CO was between 2.68‐4.57 and the last COVID‐19‐related symptoms were recent (within 19 days).

Conclusion

SARS‐CoV‐2 IgG immunoassays (S/CO) can be used to predict high anti‐SARS‐CoV‐2 nAbs titers. This study has proposed different criteria for identifying donors with ≥1:160 nAbs titers, all with high efficacy.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.11.20210005: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All candidates provided written informed consent and tested negative for SARS-CoV-2 by RT-PCR.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Briefly, 5×104 cells/mL of Vero cells (ATCC CCL-81) were seeded 24 hours before the infection in a 96-well plate.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    The predictive value of immunoassays tests (Abbott and Euroimmun) for the identification of nAbs ≥ 160 was assessed using ROC curve graphs.19 Then, the sensitivity, specificity, predictive values and accuracy of four cut-off points obtained by different methods were calculated: a) The Youden’s index method which maximizes the sum between Sensitivity and Specificity; b) The ‘Maximum Efficiency’ method which is based on the maximization of the frequency of cases correctly classified (true positives or true negatives); c) The ‘PROC01’ method which is the point on the ROC curve closest to the point to the point (0,1) or upper left corner of the graph; d) a last method which established a fixed value for sensitivity (= 90%) and sought to maximize specificity.[ref 19/20] To validate the proposed donation criteria, the total sample studied was divided into two parts (development sample and validation sample) according to the study enrollment date.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    All analyzes were performed in the R environment using RStudio software.
    RStudio
    suggested: (RStudio, RRID:SCR_000432)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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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  2. Version published to 10.1111/trf.16268
  3. Version published to 10.1101/2020.10.11.20210005v1 on medRxiv