Sensitivity of SARS-CoV-2 RNA polymerase chain reaction using a clinical and radiological reference standard

Abstract

Objectives Diagnostic tests for SARS-CoV-2 are important for epidemiology, clinical management, and infection control. Limitations of oro-nasopharyngeal real-time PCR sensitivity have been described based on comparisons of single tests with repeated sampling. We assessed SARS-CoV-2 PCR clinical sensitivity using a clinical and radiological reference standard. Methods Between March-May 2020, 2060 patients underwent thoracic imaging and SARS-CoV-2 PCR testing. Imaging was independently double- or triple-reported (if discordance) by blinded radiologists according to radiological criteria for COVID-19. We excluded asymptomatic patients and those with alternative diagnoses that could explain imaging findings. Associations with PCR-positivity were assessed with binomial logistic regression. Results 901 patients had possible/probable imaging features and clinical symptoms of COVID-19 and 429 patients met the clinical and radiological reference case definition. SARS-CoV-2 PCR sensitivity was 68% (95% confidence interval 64-73), was highest 7-8 days after symptom onset (78% (68-88)) and was lower among current smokers (adjusted odds ratio 0.23 (0.12-0.42) p<0.001). Conclusions In patients with clinical and imaging features of COVID-19, PCR test sensitivity was 68%, and was lower among smokers; a finding that could explain observations of lower disease incidence and that warrants further validation. PCR tests should be interpreted considering imaging, symptom duration and smoking status.

When to test for COVID-19 using real-time reverse transcriptase polymerase chain reaction: a systematic review

“…On the other hand, the studies representing larger populations demonstrated means similar those identified in our review ( Buonafine et al, 2020 ;Xia et al, 2020 ;Chen et al, 2021 ;Flores-Silva et al, 2021 ;Gu et al, 2021 ;Ji et al, 2021 ;Stockdale et al, 2021 ;˙I ¸s lek and Balcı, 2022 ). A cross-sectional study of 1072 patients ( Flores-Silva et al, 2021 ) found that the median time from symptom onset to diagnosis was 7 days, but the time varied from 6 to 10 days.…”

Current tobacco use and COVID-19 diagnoses in a cohort of adult clients of public dental clinics in Sweden

“…Another possibility for a non-causal negative association between smoking and COVID-19 diagnoses may be a relatively lower sensitivity of the test of choice (SARS-CoV-2 RNA polymerase chain reaction) among current smokers 31 .…”

Swab and Sputum SARS-CoV-2 RNA-Negative, CT-Positive, Symptomatic Contacts of COVID-19 Cases: A Hypothesis-Generating Prospective Population-Based Cohort Study of Eight Clusters

“…SARS-CoV-2 RNA test is the golden standard and the most commonly used method for diagnosing COVID-19 across guidelines and regulations, and in this study, all suspected cases and the contacts immediately underwent SARS-CoV-2 RNA testing by rRT-PCR assays of respiratory (throat swab and sputum) specimens, which are the most commonly recommended specimens across guidelines and regulations and which are more easily obtainable and more practicable. A Finland population-based study showed that the clinical sensitivity of SARS-CoV-2 RT-PCR testing was only moderate at best, with relatively high false-negative rates (26), and a single swab test might not be sufficient (27); the sensitivity was even lower among smokers (28). Test sensitivity increased with more test times, and were 72.4, 89.8, 97.3, and 100.0% for the first, second, third, and seventh tests, respectively (22).…”