Suitability of two rapid lateral flow immunochromatographic assays for predicting SARS‐CoV‐2 neutralizing activity of sera

  1. Arantxa Valdivia
  2. Ignacio Torres
  3. Víctor Latorre
  4. Clara Francés‐Gómez
  5. Josep Ferrer
  6. Lorena Forqué
  7. Rosa Costa
  8. Carlos Solano de la Asunción
  9. Dixie Huntley
  10. Roberto Gozalbo‐Rovira
  11. Javier Buesa
  12. Estela Giménez
  13. Jesús Rodríguez‐Díaz
  14. Ron Geller
  15. David Navarro

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Abstract

Assessment of commercial severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) immunoassays for their capacity to provide reliable information on sera neutralizing activity is an emerging need. We evaluated the performance of two commercially available lateral flow immunochromatographic assays (LFIC; Wondfo SARS‐CoV‐2 Antibody test and the INNOVITA 2019‐nCoV Ab test) in comparison with a SARS‐CoV‐2 neutralization pseudotyped assay for coronavirus disease 2019 (COVID‐19) diagnosis in hospitalized patients and investigate whether the intensity of the test band in LFIC associates with neutralizing antibody (NtAb) titers. Ninety sera were included from 51 patients with moderate to severe COVID‐19. A green fluorescent protein (GFP) reporter‐based pseudotyped neutralization assay (vesicular stomatitis virus coated with SARS‐CoV‐2 spike protein) was used. Test line intensity was scored using a 4‐level scale (0 to 3+). The overall sensitivity of LFIC assays was 91.1% for the Wondfo SARS‐CoV‐2 Antibody test, 72.2% for the INNOVITA 2019‐nCoV IgG, 85.6% for the INNOVITA 2019‐nCoV IgM, and 92.2% for the NtAb assay. Sensitivity increased for all assays in sera collected beyond day 14 after symptoms onset (93.9%, 79.6%, 93.9%, and 93.9%, respectively). Reactivities equal to or more intense than the positive control line (≥2+) in the Wondfo assay had a negative predictive value of 100% and a positive predictive value of 96.4% for high NtAb 50 titers (≥1/160). Our findings support the use of LFIC assays evaluated herein, particularly the Wondfo test, for COVID‐19 diagnosis. We also find evidence that these rapid immunoassays can be used to predict high SARS‐CoV‐2‐S NtAb 50 titers.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.23.20198713: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Research Ethics Committee of Hospital Clínico Universitario INCLIVA (March, 2020).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 Neutralizing antibody assay: A green fluorescent protein (GFP) reporter-based pseudotyped neutralization assay with a non-replicative vesicular stomatitis virus (VSV) backbone coated with SARS-CoV-2 spike (S) protein was used for neutralization assays on Vero cells, using heat-inactivated sera and a viral input of 1,250 focus-forming units, as previously described [13].
    GFP
    suggested: None
    Commercial SARS-CoV-2 IgG LFIC immunoassays: Two LFIC were evaluated: SARS-COV-2 Antibody test from Guangzhou Wondfo Biotech Co., Ltd. (China), which detects SARS-CoV-2 antibodies (IgG and IgM) in a single test band, and INNOVITA 2019-nCoV Ab Test (Beijing Innovita Biological technology, China) which detects IgG and IgM separately.
    IgM
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 Neutralizing antibody assay: A green fluorescent protein (GFP) reporter-based pseudotyped neutralization assay with a non-replicative vesicular stomatitis virus (VSV) backbone coated with SARS-CoV-2 spike (S) protein was used for neutralization assays on Vero cells, using heat-inactivated sera and a viral input of 1,250 focus-forming units, as previously described [13].
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    The analyses were performed using SPSS version 20.0 (SPSS, Chicago, IL, 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:
    The observer-dependent scoring of test line reactivity may be construed as a limitation of this study, although in fact all four readers evaluating LFIC results concurred in the categorization of all sera. Moreover, readings were consistent across different rounds of testing (not shown). In summary, our data support the use of all LFIC assays evaluated herein, particularly the Wondfo test, for COVID-19 diagnosis, especially when testing sera collected late after symptoms onset. In addition, we have shown that these rapid immunoassays can be used to infer the neutralizing activity of sera against SARS-CoV-2.

    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.

  2. Version published to 10.1002/jmv.26697
  3. Version published to 10.1101/2020.09.23.20198713v1 on medRxiv