Recent studies analyze the sensitivity and specificity for RT-PCR and chest CT for diagnosing coronavirus.
Adam Sturts, MSIV
EDITOR'S NOTE: Based on new data and guidance that has emerged since this article was originally published, Adam Sturts, MSIV, has written a follow-up to this article urging against the use of CT alone for diagnosing COVID-19.
With a constant stream of new information and data surrounding the novel coronavirus (COVID-19), a set of new studies is offering perspective and guidance on the differences between using real time reverse transcriptase-polymerase chain reaction (RT-PCR)—the reference standard for definitive COVID-19 diagnosis—and chest CT diagnostics.
A JAMA study, which was published in the form of a research letter titled “Detections of SARS-CoV-2 in Different Types of Clinical Specimens,” analyzed the sensitivity of RT-PCR testing at various tissue sites. The letter examined 1070 specimens that were collected from 205 hospitalized patients with confirmed COVID-19 in China.
Of the specimens collected, bronchoalveolar lavage fluid specimens demonstrated the highest positive rates of at 93% (n = 14). This was followed by sputum at 72% (n = 75), nasal swabs at 63% (n = 5), fibrobronchoscope brush biopsy at 46% (6/13), pharyngeal swabs at 32% (n = 126), feces at 29% (n = 44) and blood at 1% (n = 3). The authors of that study pointed out that testing of specimens from multiple sites may improve the sensitivity and reduce false-negative test results.
In another study published in Radiology, which was titled “Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 in China,” investigators found chest CT achieved higher sensitivity for diagnosis of COVID-19 as compared with initial RT-PCR from pharyngeal swab samples. This retrospective study analyzed 1014 hospitalized patients with suspected COVID-19 in Wuhan, China—with patients undergoing both serial RT-PCR testing and chest CT.
Investigators noted positive chest CT images were identified by radiologists blinded to RT-PCR results. Additionally, patients with negative RT-PCR tests but positive CT results, follow-up chest CT images were re-reviewed to confirm the imaging diagnosis. The main chest CT findings were ground-glass opacities and consolidations—most patients had bilateral chest CT findings.
Results indicated 59% (n = 601) of the patients had positive RT-PCR results and 88% (n = 888) had positive chest CT scans. In patients with negative RT-PCR results, 75% (n = 308) had positive chest CT findings. Through analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was determined to be 5.1±1.5 days and the initial positive to subsequent negative RT-PCR result was 6.9±2.3 days.
Using RT-PCR results as reference standard, the sensitivity, specificity, and accuracy of chest CT in diagnosing COVID-19 were 97% (n = 580), 25% (n = 105), and 68% (n = 685), respectively. The positive predictive value was 65% (n = 580) and the negative predictive value was 83% (n = 105). Initial RT-PCR pharyngeal swab sensitivity ranged from 66%-80% depending on assumptions made about patients with conflicting diagnostic data.
The authors noted that the data was collected from Wuhan—site of the central outbreak—and, therefore, radiologists may have been more likely to make a diagnosis of COVID-19 when typical CT features were found.
A more recent study published in NEJM entitled “Clinical Characteristics of Coronavirus Disease 2019 in China” analyzed medical records and compiled data from 1099 hospitalized patients and outpatients with laboratory-confirmed COVID-19. In this study, confirmed cases of COVID-19 were defined as a positive result on high throughput sequencing or real time RT-PCR assay of nasal and pharyngeal swab specimens.
In the study, 86% (n = 840) of patients had CT findings suggesting infection. Positive CT findings included ground-glass opacity, local patchy shadowing, bilateral patchy shadowing, or interstitial abnormalities. Additionally, no radiographic or CT abnormality was found in 17.9% (n = 157) of patients with non-severe disease and in 2.9% (n = 5) of patients with severe disease.
Of note, CDC COVID-19 Guidelines for Clinical Specimens recommends physicians collect and test a single upper respiratory nasopharyngeal swab for patients who meet the criteria for testing.
Lastly, I feel it is important to note the sensitivity of RT-PCR testing, as described above, is less than optimal. A single negative RT-PCR should not exclude COVID-19, especially if clinical suspicion is high. The combination of clinical symptoms, exposure history, typical CT imaging features, and dynamic changes must be considered to identify COVID-19 with higher sensitivity.
Adam Sturts, MSIV is a fourth-year medical student at Rowan University School of Osteopathic Medicine.Notes from Rounds is a contributor platform from HCPLive® where aspiring medical students, fellows, and early career providers provide written insight and perspective for the medical community. Those interested in contributing to COVID-19 or our coverage of other topics can contact us here.