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

Importance 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 practical implications for patient management in healthcare facilities. Objective To determine the real-life clinical sensitivity of SARS-CoV-2 RT-PCR testing. Design A retrospective study on case series from 4 March – 15 April 2020. Setting A population-based study conducted in primary and tertiary care in the Helsinki Capital Region, Finland. Participants Adults who were clinically suspected of SARS-CoV-2 infection and underwent SARS-CoV-2 RT-PCR testing, and who had sufficient data for grading of clinical suspicion of COVID-19 in their medical records were eligible. All 1,194 inpatients admitted to COVID-19 cohort wards during the study period were included. The outpatient cohort of 1,814 individuals was sampled from epidemiological line lists by systematic quasi-random sampling. Altogether 83 eligible outpatients (4.6%) and 3 inpatients (0.3%) were excluded due to insufficient data for grading of clinical suspicion. Exposures High clinical suspicion for COVID-19 was used as the reference standard for the RT-PCR test. Patients were considered to have high clinical suspicion of COVID-19 if the physician in charge recorded the suspicion on clinical grounds, or the patient fulfilled specifically defined clinical and exposure criteria. Main measures Sensitivity of SARS-CoV-2 RT-PCR by using manually curated clinical characteristics as the gold standard. Results The study population included 1,814 outpatients (mean [SD] age, 45.4 [17.2] years; 69.1% women) and 1,194 inpatients (mean [SD] age, 63.2 [18.3] years; 45.2% women). The sensitivity (95% CI) for laboratory confirmed cases, i.e. repeatedly tested patients were as follows: 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 following sensitivity values (95% CI) were observed: 67.5% (62.9–71.9%) inpatients; 34.9% (31.4–38.5%) outpatients; 47.3% (44.4–50.3%) all. Conclusions and relevance 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. Key Points Question What is the clinical sensitivity of SARS-CoV-2 RT-PCR test? Findings In this population-based retrospective study on medical records of 1,814 outpatients and 1,194 inpatients, the clinical sensitivity of SARS-CoV-2 RT-PCR was 47.3–89.9%. Meaning The 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.