COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

Diagnosis Islam N, Salameh JP, Leeflang MM, et al. Thoracic imaging tests for the diagnosis of COVID-19. Cochrane Database Syst Rev. 2020 Nov 26;11:CD013639. doi: 10.1002/14651858.CD013639.pub3.
Abstract

BACKGROUND: The respiratory illness caused by SARS-CoV-2 infection continues to present diagnostic challenges. Early research showed thoracic (chest) imaging to be sensitive but not specific in the diagnosis of coronavirus disease 2019 (COVID-19). However, this is a rapidly developing field and these findings need to be re-evaluated in the light of new research. This is the first update of this 'living systematic review'. This update focuses on people suspected of having COVID-19 and excludes studies with only confirmed COVID-19 participants.

OBJECTIVES: To evaluate the diagnostic accuracy of thoracic imaging (computed tomography (CT), X-ray and ultrasound) in people with suspected COVID-19.

SEARCH METHODS: We searched the COVID-19 Living Evidence Database from the University of Bern, the Cochrane COVID-19 Study Register, The Stephen B. Thacker CDC Library, and repositories of COVID-19 publications through to 22 June 2020. We did not apply any language restrictions.

SELECTION CRITERIA: We included studies of all designs that recruited participants of any age group suspected to have COVID-19, and which reported estimates of test accuracy, or provided data from which estimates could be computed. When studies used a variety of reference standards, we retained the classification of participants as COVID-19 positive or negative as used in the study.

DATA COLLECTION AND ANALYSIS: We screened studies, extracted data, and assessed the risk of bias and applicability concerns using the QUADAS-2 domain-list independently, in duplicate. We categorised included studies into three groups based on classification of index test results: studies that reported specific criteria for index test positivity (group 1); studies that did not report specific criteria, but had the test reader(s) explicitly classify the imaging test result as either COVID-19 positive or negative (group 2); and studies that reported an overview of index test findings, without explicitly classifying the imaging test as either COVID-19 positive or negative (group 3). We presented the results of estimated sensitivity and specificity using paired forest plots, and summarised in tables. We used a bivariate meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs).

MAIN RESULTS: We included 34 studies: 30 were cross-sectional studies with 8491 participants suspected of COVID-19, of which 4575 (54%) had a final diagnosis of COVID-19; four were case-control studies with 848 cases and controls in total, of which 464 (55%) had a final diagnosis of COVID-19. Chest CT was evaluated in 31 studies (8014 participants, 4224 (53%) cases), chest X-ray in three studies (1243 participants, 784 (63%) cases), and ultrasound of the lungs in one study (100 participants, 31 (31%) cases). Twenty-six per cent (9/34) of all studies were available only as preprints. Nineteen studies were conducted in Asia, 10 in Europe, four in North America and one in Australia. Sixteen studies included only adults, 15 studies included both adults and children and one included only children. Two studies did not report the ages of participants. Twenty-four studies included inpatients, four studies included outpatients, while the remaining six studies were conducted in unclear settings. The majority of included studies had a high or unclear risk of bias with respect to participant selection, index test, reference standard, and participant flow. For chest CT in suspected COVID-19 participants (31 studies, 8014 participants, 4224 (53%) cases) the sensitivity ranged from 57.4% to 100%, and specificity ranged from 0% to 96.0%. The pooled sensitivity of chest CT in suspected COVID-19 participants was 89.9% (95% CI 85.7 to 92.9) and the pooled specificity was 61.1% (95% CI 42.3 to 77.1). Sensitivity analyses showed that when the studies from China were excluded, the studies from other countries demonstrated higher specificity compared to the overall included studies. When studies that did not classify index tests as positive or negative for COVID-19 (group 3) were excluded, the remaining studies (groups 1 and 2) demonstrated higher specificity compared to the overall included studies. Sensitivity analyses limited to cross-sectional studies, or studies where at least two reverse transcriptase polymerase chain reaction (RT-PCR) tests were conducted if the first was negative, did not substantively alter the accuracy estimates. We did not identify publication status as a source of heterogeneity. For chest X-ray in suspected COVID-19 participants (3 studies, 1243 participants, 784 (63%) cases) the sensitivity ranged from 56.9% to 89.0% and specificity from 11.1% to 88.9%. The sensitivity and specificity of ultrasound of the lungs in suspected COVID-19 participants (1 study, 100 participants, 31 (31%) cases) were 96.8% and 62.3%, respectively. We could not perform a meta-analysis for chest X-ray or ultrasound due to the limited number of included studies.

AUTHORS' CONCLUSIONS: Our findings indicate that chest CT is sensitive and moderately specific for the diagnosis of COVID-19 in suspected patients, meaning that CT may have limited capability in differentiating SARS-CoV-2 infection from other causes of respiratory illness. However, we are limited in our confidence in these results due to the poor study quality and the heterogeneity of included studies. Because of limited data, accuracy estimates of chest X-ray and ultrasound of the lungs for the diagnosis of suspected COVID-19 cases should be carefully interpreted. Future diagnostic accuracy studies should pre-define positive imaging findings, include direct comparisons of the various modalities of interest on the same participant population, and implement improved reporting practices. Planned updates of this review will aim to: increase precision around the accuracy estimates for chest CT (ideally with low risk of bias studies); obtain further data to inform accuracy of chest X-rays and ultrasound; and obtain data to further fulfil secondary objectives (e.g. 'threshold' effects, comparing accuracy estimates across different imaging modalities) to inform the utility of imaging along different diagnostic pathways.

Ratings
Discipline / Specialty Area Score
Emergency Medicine
Hospital Doctor/Hospitalists
Internal Medicine
Infectious Disease
Pediatric Hospital Medicine
Pediatric Emergency Medicine
Respirology/Pulmonology
Pediatrics (General)
Comments from MORE raters

Emergency Medicine rater

The findings in this review show extreme heterogeneity, making the estimates of diagnostic accuracy very suspect. CT may have a reasonably high sensitivity, but in mild cases it would likely yield many false-negatives. Specificity ranged in different studies from 0% to 96%. Chest X-ray probably performed even worse, although no meta-analysis was done due to the small number of studies. The clinical bottom line is that chest imaging should not be relied on to diagnose or exclude COVID-19.

Emergency Medicine rater

Based on early COVID-19 research, both emergency medicine (https://onlinelibrary.wiley.com/doi/full/10.1111/acem.14048) and radiology (https://www.ajronline.org/doi/10.2214/AJR.20.23202) highlighted the limitations and potential harms of routine CT to augment rRT-PCR testing. Balancing COVID-19 CT-imaging potential diagnostic biases with the potential imaging risks (for radiology personnel and downstream patients awaiting CT imaging for non-COVID reasons who may become infected with COVID from the CT scanner), and uncertainties around the impact on clinical decision-making for COVID-19 amidst influenza season, I am uncertain how clinicians should use this Cochrane review to allocate imaging and avoid indication creep.

Infectious Disease rater

Unfortunately this review has pooled studies with very different designs, so the high degree of heterogeneity is not surprising. However the relatively high sensitivity was more or less a uniform finding, therefore a negative chest imaging test argues strongly against the diagnosis of COVID-19.

Internal Medicine rater

I don't see the relevance of this. This is just not how we make a diagnosis of Covid at our institution. We rely on history of exposure, symptoms, and a constellation of lab findings (prominently a PCR test, of course, but also things like D-dimer that are elevated in most patients, ABG, etc). No one single thing, or absence of a single thing, is 100% sensitive and specific. I don't think chest CT figures into this.

Internal Medicine rater

Moderately useful only. Still problems with "gold" standard, I think.

Pediatric Emergency Medicine rater

This Cochrane review looks at sensitivity and specificity of imaging modalities for diagnosis of COVID. Although about 50% of the included studies involve pediatric patients, they do not give an answer to what is the best imaging test in children, or the settings in which the recommendations apply.