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

Kortela, E.; Kirjavainen, V.; Ahava, M.; Jokiranta, S.; But, A.; Lindahl, A.; Jaaskelainen, A. E.; Jaaskelainen, A. J.; Jarvinen, A.; Jokela, P.; Kallio-Kokko, H.; Loginov, R.; Mannonen, L.; Ruotsalainen, E.; Sironen, T.; Vapalahti, O.; Lappalainen, M.; Kreivi, H.-R.; Jarva, H.; Kurkela, S.; Kekalainen, E.

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.