Thoracic imaging tests for the diagnosis of COVID-19

Cochrane COVID-19 Diagnostic Test Accuracy Group

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Abstract

BACKGROUND: Our March 2021 edition of this review showed thoracic imaging computed tomography (CT) to be sensitive and moderately specific in diagnosing COVID-19 pneumonia. This new edition is an update of the review.

OBJECTIVES: Our objectives were to evaluate the diagnostic accuracy of thoracic imaging in people with suspected COVID-19; assess the rate of positive imaging in people who had an initial reverse transcriptase polymerase chain reaction (RT-PCR) negative result and a positive RT-PCR result on follow-up; and evaluate the accuracy of thoracic imaging for screening COVID-19 in asymptomatic individuals. The secondary objective was to assess threshold effects of index test positivity on accuracy.

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 17 February 2021. We did not apply any language restrictions.

SELECTION CRITERIA: We included diagnostic accuracy studies of all designs, except for case-control, that recruited participants of any age group suspected to have COVID-19. Studies had to assess chest CT, chest X-ray, or ultrasound of the lungs for the diagnosis of COVID-19, use a reference standard that included RT-PCR, and report estimates of test accuracy or provide data from which we could compute estimates. We excluded studies that used imaging as part of the reference standard and studies that excluded participants with normal index test results.

DATA COLLECTION AND ANALYSIS: The review authors independently and in duplicate screened articles, extracted data and assessed risk of bias and applicability concerns using QUADAS-2. We presented sensitivity and specificity per study on paired forest plots, and summarized pooled estimates in tables. We used a bivariate meta-analysis model where appropriate.

MAIN RESULTS: We included 98 studies in this review. Of these, 94 were included for evaluating the diagnostic accuracy of thoracic imaging in the evaluation of people with suspected COVID-19. Eight studies were included for assessing the rate of positive imaging in individuals with initial RT-PCR negative results and positive RT-PCR results on follow-up, and 10 studies were included for evaluating the accuracy of thoracic imaging for imagining asymptomatic individuals. For all 98 included studies, risk of bias was high or unclear in 52 (53%) studies with respect to participant selection, in 64 (65%) studies with respect to reference standard, in 46 (47%) studies with respect to index test, and in 48 (49%) studies with respect to flow and timing. Concerns about the applicability of the evidence to: participants were high or unclear in eight (8%) studies; index test were high or unclear in seven (7%) studies; and reference standard were high or unclear in seven (7%) studies. Imaging in people with suspected COVID-19 We included 94 studies. Eighty-seven studies evaluated one imaging modality, and seven studies evaluated two imaging modalities. All studies used RT-PCR alone or in combination with other criteria (for example, clinical signs and symptoms, positive contacts) as the reference standard for the diagnosis of COVID-19. For chest CT (69 studies, 28285 participants, 14,342 (51%) cases), sensitivities ranged from 45% to 100%, and specificities from 10% to 99%. The pooled sensitivity of chest CT was 86.9% (95% confidence interval (CI) 83.6 to 89.6), and pooled specificity was 78.3% (95% CI 73.7 to 82.3). Definition for index test positivity was a source of heterogeneity for sensitivity, but not specificity. Reference standard was not a source of heterogeneity. For chest X-ray (17 studies, 8529 participants, 5303 (62%) cases), the sensitivity ranged from 44% to 94% and specificity from 24 to 93%. The pooled sensitivity of chest X-ray was 73.1% (95% CI 64. to -80.5), and pooled specificity was 73.3% (95% CI 61.9 to 82.2). Definition for index test positivity was not found to be a source of heterogeneity. Definition for index test positivity and reference standard were not found to be sources of heterogeneity. For ultrasound of the lungs (15 studies, 2410 participants, 1158 (48%) cases), the sensitivity ranged from 73% to 94% and the specificity ranged from 21% to 98%. The pooled sensitivity of ultrasound was 88.9% (95% CI 84.9 to 92.0), and the pooled specificity was 72.2% (95% CI 58.8 to 82.5). Definition for index test positivity and reference standard were not found to be sources of heterogeneity. Indirect comparisons of modalities evaluated across all 94 studies indicated that chest CT and ultrasound gave higher sensitivity estimates than X-ray (P = 0.0003 and P = 0.001, respectively). Chest CT and ultrasound gave similar sensitivities (P=0.42). All modalities had similar specificities (CT versus X-ray P = 0.36; CT versus ultrasound P = 0.32; X-ray versus ultrasound P = 0.89). Imaging in PCR-negative people who subsequently became positive For rate of positive imaging in individuals with initial RT-PCR negative results, we included 8 studies (7 CT, 1 ultrasound) with a total of 198 participants suspected of having COVID-19, all of whom had a final diagnosis of COVID-19. Most studies (7/8) evaluated CT. Of 177 participants with initially negative RT-PCR who had positive RT-PCR results on follow-up testing, 75.8% (95% CI 45.3 to 92.2) had positive CT findings. Imaging in asymptomatic PCR-positive people For imaging asymptomatic individuals, we included 10 studies (7 CT, 1 X-ray, 2 ultrasound) with a total of 3548 asymptomatic participants, of whom 364 (10%) had a final diagnosis of COVID-19. For chest CT (7 studies, 3134 participants, 315 (10%) cases), the pooled sensitivity was 55.7% (95% CI 35.4 to 74.3) and the pooled specificity was 91.1% (95% CI 82.6 to 95.7).

AUTHORS' CONCLUSIONS: Chest CT and ultrasound of the lungs are sensitive and moderately specific in diagnosing COVID-19. Chest X-ray is moderately sensitive and moderately specific in diagnosing COVID-19. Thus, chest CT and ultrasound may have more utility for ruling out COVID-19 than for differentiating SARS-CoV-2 infection from other causes of respiratory illness. The uncertainty resulting from high or unclear risk of bias and the heterogeneity of included studies limit our ability to confidently draw conclusions based on our results.

Original languageEnglish
Article numberCD013639
Number of pages242
JournalCochrane Database of Systematic Reviews
Volume5
Issue number5
DOIs
Publication statusPublished - 16 May 2022

Bibliographical note

Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.

Funding Information:
Jonathan Deeks is a UK National Institute for Health Research (NIHR) Senior Investigator Emeritus. Yemisi Takwoingi is supported by a NIHR Postdoctoral Fellowship. Jonathan Deeks, Jacqueline Dinnes, and Yemisi Takwoingi are supported by the NIHR Birmingham Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.

The CIDG editorial base is funded by UK aid from the UK government for the benefit of low-and middle-income countries (project number 300342-104). The views expressed do not necessarily reflect the UK government’s official policies.

Members of the Cochrane COVID-19 Diagnostic Test Accuracy Review Group include the following. The project team (Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Leeflang MMG, Spijker R, Hooft L, Van den Bruel A, McInnes MDF, Emperador D, Dittrich S); The systematic review teams for each review The project team (Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Leeflang MMG, Spijker R, Hooft L, Van den Bruel A, McInnes MDF, Emperador D, Dittrich S); The systematic review teams for each review Molecular, antigen, and antibody tests (Adriano A, Beese S, Dretzke J, Ferrante di Ruffano L, Harris I, Price M, Taylor-Phillips S) Signs and symptoms (Stuyf T, Domen J, Horn S) Routine laboratory markers (Yang B, Langendam M, Ochodo E, Guleid F, Holtman G, Verbakel J, Wang J, Stegeman I) Imaging tests (Islam N, Ebrahimzadeh S, Dawit H, Salameh JP, Kazi S, Fabiano N, Treanor L, Absi M, Ahmad F, Rooprai P, Al Khalil A, Harper K, Kamra N, Van Der Pol CB, Prager R, Hare SS, Dennie C, Jenniskens K, Korevaar DA, Cohen JF, van de Wijgert J, Wang J, Pena E, Sabongui S) Molecular, antigen, and antibody tests (Adriano A, Beese S, Dretzke J, Ferrante di Ruffano L, Harris I, Price M, Taylor-Phillips S) Signs and symptoms (Stuyf T, Domen J, Horn S) Routine laboratory markers (Yang B, Langendam M, Ochodo E, Guleid F, Holtman G, Verbakel J, Wang J, Stegeman I) Imaging tests (Islam N, Ebrahimzadeh S, Dawit H, Salameh JP, Kazi S, Fabiano N, Treanor L, Absi M, Ahmad F, Rooprai P, Al Khalil A, Harper K, Kamra N, Van Der Pol CB, Prager R, Hare SS, Dennie C, Jenniskens K, Korevaar DA, Cohen JF, van de Wijgert J, Wang J, Pena E, Sabongui S) The wider team of systematic reviewers from University of Birmingham, UK who assisted with title and abstract screening across the entire suite of reviews for the diagnosis of COVID-19 (Agarwal R, Baldwin S, Berhane S, Herd C, Kristunas C, Quinn L, Scholefield B). The wider team of systematic reviewers from University of Birmingham, UK who assisted with title and abstract screening across the entire suite of reviews for the diagnosis of COVID-19 (Agarwal R, Baldwin S, Berhane S, Herd C, Kristunas C, Quinn L, Scholefield B). We thank Dr Jane Cunningham (World Health Organization) for participation in technical discussions and comments on the manuscript. The Cochrane Infectious Diseases Group (CIDG) managed the editorial process on this review update version. The CIDG Editor was Professor Mical Paul, DTA Editor was Professor Gianni Virgili (Contact Editor), and the Sign-off Editor was Professor Paul Garner. We thank Heather Maxwell (Cochrane Copy Edit Support) who copyedited this review update version. For previous published review versions, we thank the Cochrane Central Editorial Service for managing the editorial process (Salameh 2020a; Islam 2020; Islam 2021). We thank Helen Wakeford and Anne-Marie Stephani (Managing Editors, Central Editorial Service, Cochrane); Gianni Virgili (Contact Editor), Sophie Beese and Bella Harris (Managing Editors) and Marta Roqué (statistical peer reviewer) from the Cochrane Diagnostic Test Accuracy Reviews Editorial Team; Robin Featherstone (Central Editorial Service, Cochrane) for search peer review; peer reviewers Paul Garner and Robert Walton; consumer referee Shirley Hall; and Denise Mitchell (Central Editorial Service, Cochrane). The CIDG editorial base is funded by UK aid from the UK government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed do not necessarily reflect the UK government’s official policies. Jonathan Deeks is a UK National Institute for Health Research (NIHR) Senior Investigator Emeritus. Yemisi Takwoingi is supported by a NIHR Postdoctoral Fellowship. Jonathan Deeks, Jacqueline Dinnes, and Yemisi Takwoingi are supported by the NIHR Birmingham Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.

Project number: 300342-104 National Institute for Health Research (NIHR), UK Government of Ontario Ministry of Health COVID-19 Rapid Response Research Grant program, Canada University of Ottawa Faculty of Medicine COVID-19 Pandemic Response Funding Program, Canada

Publisher Copyright:
Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.

Keywords

  • COVID-19/diagnostic imaging
  • Humans
  • SARS-CoV-2
  • Sensitivity and Specificity
  • Tomography, X-Ray Computed
  • Ultrasonography

ASJC Scopus subject areas

  • Pharmacology (medical)

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