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.

Keywords: COVID-19; Diagnostic X-Ray; Diagnostic testing; Radiology; Real-time polymerase chain reaction; SARS-CoV-2; Sensitivity and specificity.

Fig. 1

Flowchart of included patients in study of SARS-CoV-2 PCR sensitivity^aClinical reasons for exclusion, representing alternative aetiologies for imaging findings reported as high probability of COVID-19 (n=15), comprised: pulmonary oedema due to cardiac failure (n=7), aspiration pneumonia (n=5), massive transfusion following haemorrhage (n=1), interstitial lung disease (n=1), anti-glomerular basement membrane lung disease (n=1).

Fig. 2

Clinical sensitivity of SARS-CoV-2 PCR relative to clinical and radiological reference standard, stratified by subgroups.

Fig. 3

: Predicted sensitivity of PCR test according to duration of symptoms^{a a}Prediction plot of PCR positivity using four-knot restricted cubic spline for duration of symptoms at time of PCR testing. Knots were introduced at 0, 5, 10 and 22 days. Shaded area represents 95% confidence intervals.