Sensitivity, Specificity and Predictive Values of Molecular and Serological Tests for COVID-19: A Longitudinal Study in Emergency Room

  1. Zeno Bisoffi
  2. Elena Pomari
  3. Michela Deiana
  4. Chiara Piubelli
  5. Niccolò Ronzoni
  6. Anna Beltrame
  7. Giulia Bertoli
  8. Niccolò Riccardi
  9. Francesca Perandin
  10. Fabio Formenti
  11. Federico Gobbi
  12. Dora Buonfrate
  13. Ronaldo Silva

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background: We assessed the sensitivity, specificity and positive and negative predictive value (PPV and NPV) of molecular and serological tests for the diagnosis of SARS-CoV-2 infection. Methods: A total of 346 patients were enrolled in the emergency room. We evaluated three Reverse Transcriptase-real time PCRs (RT-PCRs) including six different gene targets, five serologic rapid diagnostic tests (RDT) and one ELISA. The final classification of infected/non-infected patients was performed using Latent Class Analysis combined with clinical re-assessment of incongruous cases. Results: Out of these, 24.6% of patients were classified as infected. The molecular test RQ-SARS-nCoV-2 showed the highest performance with 91.8% sensitivity, 100% specificity, 100.0% PPV and 97.4% NPV respectively. Considering the single gene targets, S and RdRp of RQ-SARS-nCoV-2 had the highest sensitivity (94.1%). The in-house RdRp presented the lowest sensitivity (62.4%). The specificity ranged from 99.2% for in-house RdRp and N2 to 95.0% for E. The PPV ranged from 97.1% of N2 to 85.4% of E and the NPV from 98.1% of S to 89.0% of in-house RdRp. All serological tests had < 50% sensitivity and low PPV and NPV. VivaDiag IgM (RDT) had 98.5% specificity, with 84.0% PPV, but 24.7% sensitivity. Conclusion: Molecular tests for SARS-CoV-2 infection showed excellent specificity, but significant differences in sensitivity. Serological tests have limited utility in a clinical context.

Article activity feed

  1. Version published to 10.3390/diagnostics10090669
  2. ScreenIT

    SciScore for 10.1101/2020.08.09.20171355: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Ethical clearance: The study protocol was approved by the pertinent Ethical Committee (Comitato Etico per la Sperimentazione clinica delle Province di Verona e Rovigo, Protocol N. 19408, 2nd April 2020 and following amendment, protocol N. 33102, approved on 10th June 2020).
    Consent: All the patients included gave their consent to the storage of biological samples in the “Tropica Biobank” and use of related results for research purposes, as per routine procedure in our hospital.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data analysis were performed using SAS software, version 9.4 (SAS Institute, Inc., Cary, NC, USA).
    SAS
    suggested: (SASqPCR, RRID:SCR_003056)
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)
    Protocol registration: The protocol has been registered at http://www.isrctn.com/ with the ID ISRCTN13990999.
    http://www.isrctn.com/
    suggested: (ISRCTN Registry, RRID:SCR_006087)

    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:
    Limitations: The sample size was slightly lower than the calculated number of 376 patients, due to the sharply decreasing number of new cases in the last period of the investigation. However, samples from almost all patients recruited were subsequently analyzed as there were no altered or invalid specimens, reaching a final final number of 346 patients, which was close to the planned sample size. Despite the longitudinal study design, some clinical data were missing for a number of patients, which also reflects the inherent difficulties in performing clinical studies in emergency situations. However, for most variables included in the model the data set was sufficiently complete.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    ISRCTN13990999NANA

    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 10.1101/2020.08.09.20171355v1 on medRxiv