Real-life clinical sensitivity of SARS-CoV-2 RT-PCR test in symptomatic patients

  1. Elisa Kortela
  2. Vesa Kirjavainen
  3. Maarit J. Ahava
  4. Suvi T. Jokiranta
  5. Anna But
  6. Anna Lindahl
  7. Anu E. Jääskeläinen
  8. Annemarjut J. Jääskeläinen
  9. Asko Järvinen
  10. Pia Jokela
  11. Hannimari Kallio-Kokko
  12. Raisa Loginov
  13. Laura Mannonen
  14. Eeva Ruotsalainen
  15. Tarja Sironen
  16. Olli Vapalahti
  17. Maija Lappalainen
  18. Hanna-Riikka Kreivi
  19. Hanna Jarva
  20. Satu Kurkela
  21. Eliisa Kekäläinen

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Abstract

Understanding the false negative rates of SARS-CoV-2 RT-PCR testing is pivotal for the management of the COVID-19 pandemic and it has implications for patient management. Our aim was to determine the real-life clinical sensitivity of SARS-CoV-2 RT-PCR.

Methods

This population-based retrospective study was conducted in March–April 2020 in the Helsinki Capital Region, Finland. Adults who were clinically suspected of SARS-CoV-2 infection and underwent SARS-CoV-2 RT-PCR testing, with sufficient data in their medical records for grading of clinical suspicion were eligible. In addition to examining the first RT-PCR test of repeat-tested individuals, we also used high clinical suspicion for COVID-19 as the reference standard for calculating the sensitivity of SARS-CoV-2 RT-PCR.

Results

All 1,194 inpatients (mean [SD] age, 63.2 [18.3] years; 45.2% women) admitted to COVID-19 cohort wards during the study period were included. The outpatient cohort of 1,814 individuals (mean [SD] age, 45.4 [17.2] years; 69.1% women) was sampled from epidemiological line lists by systematic quasi-random sampling. The sensitivity (95% CI) for laboratory confirmed cases (repeat-tested patients) was 85.7% (81.5–89.1%) inpatients; 95.5% (92.2–97.5%) outpatients, 89.9% (88.2–92.1%) all. When also patients that were graded as high suspicion but never tested positive were included in the denominator, the sensitivity (95% CI) was: 67.5% (62.9–71.9%) inpatients; 34.9% (31.4–38.5%) outpatients; 47.3% (44.4–50.3%) all.

Conclusions

The clinical sensitivity of SARS-CoV-2 RT-PCR testing was only moderate at best. The relatively high false negative rates of SARS-CoV-2 RT-PCR testing need to be accounted for in clinical decision making, epidemiological interpretations, and when using RT-PCR as a reference for other tests.

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  1. Version published to 10.1371/journal.pone.0251661
  2. ScreenIT

    SciScore for 10.1101/2020.11.01.20223107: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study complies with the STARD reporting guidelines15, and it was approved by the local review board (HUS/157/2020-29).
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisThe clinical suspicion for COVID-19 disease was graded as follows: Sample size calculation: We estimated the minimum sample size needed for outpatients based on Bujang et al17, with a minimal statistical power of 80% and type I error <0.05.
    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:
    We sought to overcome this limitation by including a large cohort of outpatients. From an epidemiological point-of-view, understanding the clinical sensitivity for mild cases is important. A recent preprint reported an RT-PCR sensitivity of 64% for exposed family members systemically tested with serology.23 This is in line with our sensitivity estimation for inpatients. Our analysis was done in a low prevalence setting. Thus, the negative predictive value for the RT-PCR test was high (89%) for the outpatients even though the clinical sensitivity was low (35%), assuming all COVID-19 excluded cases were true negatives. In light of clinical judgement, false negative rate was high which could reduce the negative predictive value of testing. This is particularly problematic when the prevalence of the disease increases. In such settings, it will impair effective use of wide-spread testing. For health-care facilities the message of our data is different: a single negative result cannot be trusted to rule out COVID-19 in patients with suitable symptoms. Our data show that the sensitivity of the repeat-tested inpatients was high (86%), and in line with previous reports on repeated testing.9,22 When the sensitivity of the COVID-19 PCR test was judged based on the laboratory confirmed and high clinical suspicion patients the estimated sensitivity of the test dropped to around 68%. Our results emphasize the importance of repeated sampling but it also highlights the importance to evaluate...

    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 10.1101/2020.11.01.20223107v1 on medRxiv