COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Diagnosis Schulze-Hagen M, Hubel C, Meier-Schroers M, et al. Low-Dose Chest CT for the Diagnosis of COVID-19. Dtsch Arztebl Int. 2020 Jun 1;117(22-23):389-395. doi: 10.3238/arztebl.2020.0389.
Abstract

BACKGROUND: Only limited evidence has been available to date on the accuracy of systematic low-dose chest computed tomography (LDCT) use in the diagnosis of COVID-19 in patients with non-specific clinical symptoms.

METHODS: The COVID-19 Imaging Registry Study Aachen (COVID-19-Bildgebungs-Register Aachen, COBRA) collects data on imaging in patients with COVID-19. Two of the COBRA partner hospitals (RWTH Aachen University Hospital and Dueren Hospital) systematically perform reverse transcriptase polymerase chain reaction (RT-PCR) from nasopharyngeal swabs as well as LDCT in all patients presenting with manifestations that are compatible with COVID-19. In accordance with the COV-RADS protocol, the LDCT scans were prospectively evaluated before the RT-PCR findings were available in order to categorize the likelihood of COVID-19.

RESULTS: From 18 March to 5 May 2020, 191 patients with COVID-19 manifestations (117 male, age 65 ± 16 years) underwent RT-PCR testing and LDCT. The mean time from the submission of the sample to the availability of the RT-PCR findings was 491 minutes (interquartile range [IQR: 276-1066]), while that from the performance of the CT to the availability of its findings was 9 minutes (IQR: 6-11). A diagnosis of COVID-19 was made in 75/191 patients (39%). The LDCT was positive in 71 of these 75 patients and negative in 106 of the 116 patients without COVID-19, corresponding to 94.7% sensitivity (95% confidence interval [86.9; 98.5]), 91.4% specificity [84.7; 95.8], positive and negative predictive values of 87.7% [78.5; 93.9] and 96.4% [91.1; 98.6], respectively, and an AUC (area under the curve) of 0.959 [0.930; 0.988]. The initial RT-PCR test results were falsely negative in six patients, yielding a sensitivity of 92.0% [83.4; 97.0]; these six patients had positive LDCT findings. 47.4% of the LDCTs that were negative for COVID-19 (55/116) exhibited pathological pulmonary changes, including infiltrates, that were correctly distinguished from SARS-CoV-2 related changes.

CONCLUSION: In patients with symptoms compatible with COVID-19, LDCT can esablish the diagnosis of COVID-19 with comparable sensitivity to RT-PCR testing. In addition, it offers a high specificity for distinguishing COVID-19 from other diseases associated with the same or similar clinical symptoms. We propose the systematic use of LDCT in addition to RT-PCR testing because it helps correct false-negative RT-PCR results, because its results are available much faster than those of RT-PCRtesting, and because it provides additional diagnostic information useful for treatment planning regardless of the type of the infectious agent.

Ratings
Discipline / Specialty Area Score
Hospital Doctor/Hospitalists
Internal Medicine
Respirology/Pulmonology
General Internal Medicine-Primary Care(US)
Family Medicine (FM)/General Practice (GP)
Emergency Medicine
Infectious Disease
Comments from MORE raters

Emergency Medicine rater

The significant flaws in COVID-19 diagnostic research were recently highlighted by emergency medicine (https://onlinelibrary.wiley.com/doi/full/10.1111/acem.14048) and radiology (https://www.ajronline.org/doi/10.2214/AJR.20.23202). These previous studies discuss the implications of failure to adhere to STARD reporting standards (https://www.equator-network.org/reporting-guidelines/stard/). In addition, studies advocating for a CT-based approach to COVID-19 diagnostics (including the current study) neglect measurable harms of such an approach highlighted by both EM and radiology reviews.

Emergency Medicine rater

This study evaluates the use of low-dose computed tomography (LDCT) compared with RT-PCR. It included 191 patients, of which 75 were diagnosed with COVID-19. Sensitivity of LDCT was 94.7 (95% CI 86.9-98.5) and specificity was 91.4% (95% CI 84.7-95.8). Although this was similar overall to RT-PCR, inter-observer variability in CT interpretation was not evaluated, and follow-up of concordant negative results was not performed. Limited patient information was provided, preventing close evaluation of how "sick" the patients were. They predicted COVID-19 on imaging based on the COVRADs classification; however, one is left with the question of whether LDCT truly changes clinical management. A test that does not change management is likely unnecessary, even more so when associated with potential harms.

Emergency Medicine rater

Interesting and practical information, but the study design is unclear. This seems to be a retrospective study, which is subject to biases inherent to the design.

Emergency Medicine rater

It's not clear from this which is the index and which is the reference test as some of the RT-PCR test results were judged falsely negative based on the LDCT findings.

General Internal Medicine-Primary Care(US) rater

The data are compelling. Although it may take longer than 9 minutes for a low-dose CT to be read outside Germany, the images and/or interpretation may still compete favorably with the timing results for COVID-PCR.

Hospital Doctor/Hospitalists rater

With the current pandemic showing no signs of ceasing, it is becoming increasingly important to diagnose patients with active COVID-19 disease as soon as possible. We saw earlier in the diagnosis out of China, that patients presented with abnormal CT findings before showing seropositivity on PCR testing. These findings confirm the suspicion that many patients will have early pulmonary findings (confirmed by CDC stating that the order of symptoms are typically fever, cough, then shortness of breath). The limitation of CT machines needing to be de-contaminated, however, will likely decrease the ability to implement these findings.

Infectious Disease rater

This study suggests that low-dose chest CT is at least as sensitive as the current RT-PCR. Unfortunately, it doesn't give details on time from onset of symptoms, which diminishes its value.

Infectious Disease rater

Low-dose CT scans for diagnosis of COVID-19 continues to go back and forth. Although there's little question that it can be a sensitive test, as is described here, the feasibility and cost-effectiveness of the strategy remains questionable. Further, the specificity of this test, reported for late spring, hasn't really been adequately tested for the upcoming flu season, when a competing respiratory virus will need to be distinguished from COVID for public health and treatment purposes.

Internal Medicine rater

This literature is very mixed and I am not sure we can rely on this just yet. This also exposes more patients and staff when we have to send people for a CT scan.

Respirology/Pulmonology rater

In this study setting for Covid-19, low-dose chest CT scanning had better positive and negative predictive value with faster results than did nasal swab PCR. As with most testing procedures, the quality of the test site is key, so the results may not be generally applicable. Also, inter-reader comparability was not assessed in this study.

Respirology/Pulmonology rater

This study of diagnosis finds that low-dose CT was highly accurate for diagnosing COVID-19, compared with a reference standard of NP swab RT-PCR and clinical follow-up. They included only patients who had both NP swabs and CTs and it`s not clear how many patients with symptoms compatible with COVID-19 were excluded because they did not undergo one or the other test. To the extent that this happened, the study would exaggerate the observed accuracy of CT and it also makes generalizability unclear (e.g., what proportion of patients with non-respiratory presentations of COVID-19 got CTs?). Not clear how long patients were followed clinically to assess whether their RT-PCR was a false-negative, but these findings likely make the strongest case to date for the role of CT in the diagnosis of COVID-19.

Respirology/Pulmonology rater

A very interesting and well done study. The mechanism of comparing standard of care was robust (i.e., the RT-PCR for COVID-19 with LDCT scan). The evidence obtained from this study certainly behooves further studies to evaluate LDCT use. The concern for radiation exposure is explained by the authors as less than annual natural exposure. The time to answer with LDCT is faster than with RT-PCR, however, there is the question of cost that remains unanswered. How does LDCT compare with RT-PCR in terms of cost?