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

PLoS One. 2021 May 21;16(5):e0251661. doi: 10.1371/journal.pone.0251661. eCollection 2021.

Abstract

Background: 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • COVID-19 Nucleic Acid Testing / methods
  • COVID-19 Nucleic Acid Testing / standards*
  • False Negative Reactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Random Allocation
  • Reagent Kits, Diagnostic / standards

Substances

  • Reagent Kits, Diagnostic

Grants and funding

This work was supported by Academy of Finland (ELKE, grant no 308913) and Doctoral Programme in Biomedicine, Faculty of Medicine, University of Helsinki (SJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.