Predictors of negative first SARS-CoV-2 RT-PCR despite final diagnosis of COVID-19 and association with outcome

  1. Jean-Baptiste Lascarrou
  2. Gwenhael Colin
  3. Aurélie Le Thuaut
  4. Nicolas Serck
  5. Mickael Ohana
  6. Bertrand Sauneuf
  7. Guillaume Geri
  8. Jean-Baptiste Mesland
  9. Gaetane Ribeyre
  10. Claire Hussenet
  11. Anne Sophie Boureau
  12. Thomas Gille

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Abstract

Reverse transcriptase-polymerase chain reaction (RT-PCR) testing is an important tool for diagnosing coronavirus disease 2019 (COVID-19). However, performance concerns have emerged recently, notably regarding sensitivity. We hypothesized that the clinical, biological, and radiological characteristics of patients with a false-negative first RT-PCR test and a final diagnosis of COVID-19 might differ from those of patients with a positive first RT-PCR test. We conducted a multicenter matched case–control study in COVID-19 patients. Patients with a negative first RT-PCR test were matched to patients with a positive first RT-PCR test on age, sex, and initial admission unit (ward or intensive care). We included 80 cases and 80 controls between March 30, and June 22, 2020. Neither mortality at hospital discharge nor hospital stay length differed between the two groups ( P  = 0.80 and P  = 0.54, respectively). By multivariate analysis, two factors were independently associated with a lower risk of a first false-negative test, namely, headache (adjusted OR [aOR], 0.07; 95% confidence interval [95% CI], 0.01–0.49]; P  = 0.007) and fatigue/malaise (aOR, 0.16; 95% CI, 0.03–0.81; P  = 0.027); two other factors were independently associated with a higher risk of a first false-negative test, namely, platelets > 207·10 3  mm −3 (aOR, 3.81; 95% CI, 1.10–13.16]; P  = 0.034) and C-reactive protein > 79.8 mg·L −1 (aOR, 4.00; 95% CI, 1.21–13.19; P  = 0.023). Patients with suspected COVID-19 whose laboratory tests indicating marked inflammation were at higher risk of a first false-negative RT-PCR test. Strategies involving serial RT-PCR testing must be rigorously evaluated.

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  1. Version published to 10.1038/s41598-021-82192-6
  2. Version published to 10.1101/2020.09.14.20194001v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.09.14.20194001: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics: The study was approved by the appropriate ethics committees (For France: Comité d’éthique de la Société de Réanimation de Langue Française, #20–26; and for Belgium: Comité d’Ethique 045 Clinique Saint Pierre) which waived consent according to collected data.
    Consent: Ethics: The study was approved by the appropriate ethics committees (For France: Comité d’éthique de la Société de Réanimation de Langue Française, #20–26; and for Belgium: Comité d’Ethique 045 Clinique Saint Pierre) which waived consent according to collected data.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Some limitations of our study must be highlighted. First, negative RT-PCR testing can be related to other disease. However, 45 (59.96%) of cases were also negative for other pathogen research during their hospital length stay and final diagnosis of COVID-19 was performed according to multimodal strategy including chest CT-scans in 88.75% of cases. Second, some issues could occur during technical sampling of RT-PCR but all RT-PCR were performed in hospitals with trained nurses and dedicated protocol to ensure high adherence to methods of RT-PCR collection. Third, our sample size is limited, but we chose to restrain inclusion of patients with robust arguments for COVID-19 according to other diagnostic methods (especially chest CT-scans) with limited availability during epidemic wave in Europe. Last, we included patients from several centers with different RT-PCR detection kits. However, evidence suggest similar performance of available RT-PCR kits (22, 23).

    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.

  4. Version published to 10.1101/2020.09.14.20194001v1 on medRxiv