Nayaar Islam1,2, Jean-Paul Salameh1, Mariska Mg Leeflang3, Lotty Hooft4, Trevor A McGrath1, Christian B van der Pol5, Robert A Frank1, Sakib Kazi1, Ross Prager6, Samanjit S Hare7, Carole Dennie1,8, René Spijker4,9, Jonathan J Deeks10,11, Jacqueline Dinnes10,11, Kevin Jenniskens4, Daniël A Korevaar12, Jérémie F Cohen13, Ann Van den Bruel14, Yemisi Takwoingi10,11, Janneke van de Wijgert4,15, Junfeng Wang16, Matthew Df McInnes1,2. 1. Department of Radiology, University of Ottawa, Ottawa, Canada. 2. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada. 3. Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands. 4. Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. 5. Department of Radiology, McMaster University, Hamilton, Canada. 6. Department of Medicine, University of Ottawa, Ottawa, Canada. 7. Department of Radiology, Royal Free London NHS Trust, London, UK. 8. Department of Medical Imaging, The Ottawa Hospital, Ottawa, Canada. 9. Medical Library, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Amsterdam, Netherlands. 10. NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK. 11. Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK. 12. Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 13. Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS), Inserm UMR1153, Université de Paris, Paris, France. 14. Academic of Primary Care, KU Leuven, Leuven, Belgium. 15. Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, UK. 16. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
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.
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-19participants. 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-19participants (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-19participants 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-19participants (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-19participants (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.
Authors: Jacqueline Dinnes; Pawana Sharma; Sarah Berhane; Susanna S van Wyk; Nicholas Nyaaba; Julie Domen; Melissa Taylor; Jane Cunningham; Clare Davenport; Sabine Dittrich; Devy Emperador; Lotty Hooft; Mariska Mg Leeflang; Matthew Df McInnes; René Spijker; Jan Y Verbakel; Yemisi Takwoingi; Sian Taylor-Phillips; Ann Van den Bruel; Jonathan J Deeks Journal: Cochrane Database Syst Rev Date: 2022-07-22
Authors: Sanam Ebrahimzadeh; Nayaar Islam; Haben Dawit; Jean-Paul Salameh; Sakib Kazi; Nicholas Fabiano; Lee Treanor; Marissa Absi; Faraz Ahmad; Paul Rooprai; Ahmed Al Khalil; Kelly Harper; Neil Kamra; Mariska Mg Leeflang; Lotty Hooft; Christian B van der Pol; Ross Prager; Samanjit S Hare; Carole Dennie; René Spijker; Jonathan J Deeks; Jacqueline Dinnes; Kevin Jenniskens; Daniël A Korevaar; Jérémie F Cohen; Ann Van den Bruel; Yemisi Takwoingi; Janneke van de Wijgert; Junfeng Wang; Elena Pena; Sandra Sabongui; Matthew Df McInnes Journal: Cochrane Database Syst Rev Date: 2022-05-16
Authors: Fabian F Fay; Carlos Arturo Alvarez-Moreno; Pablo E Bonvehi; Carolina Cucho Espinoza; Marco Luis Herrera Hidalgo; Marcel Marcano-Lozada; Carlos M Perez; Alvaro Pulchinelli; Klever Vinicio Sáenz-Flor; Antonio Condino-Neto Journal: Int J Infect Dis Date: 2021-05-20 Impact factor: 12.074
Authors: Thomas Struyf; Jonathan J Deeks; Jacqueline Dinnes; Yemisi Takwoingi; Clare Davenport; Mariska Mg Leeflang; René Spijker; Lotty Hooft; Devy Emperador; Julie Domen; Sebastiaan R A Horn; Ann Van den Bruel Journal: Cochrane Database Syst Rev Date: 2021-02-23
Authors: Nayaar Islam; Sanam Ebrahimzadeh; Jean-Paul Salameh; Sakib Kazi; Nicholas Fabiano; Lee Treanor; Marissa Absi; Zachary Hallgrimson; Mariska Mg Leeflang; Lotty Hooft; Christian B van der Pol; Ross Prager; Samanjit S Hare; Carole Dennie; René Spijker; Jonathan J Deeks; Jacqueline Dinnes; Kevin Jenniskens; Daniël A Korevaar; Jérémie F Cohen; Ann Van den Bruel; Yemisi Takwoingi; Janneke van de Wijgert; Johanna Aag Damen; Junfeng Wang; Matthew Df McInnes Journal: Cochrane Database Syst Rev Date: 2021-03-16
Authors: Jacqueline Dinnes; Jonathan J Deeks; Ada Adriano; Sarah Berhane; Clare Davenport; Sabine Dittrich; Devy Emperador; Yemisi Takwoingi; Jane Cunningham; Sophie Beese; Janine Dretzke; Lavinia Ferrante di Ruffano; Isobel M Harris; Malcolm J Price; Sian Taylor-Phillips; Lotty Hooft; Mariska Mg Leeflang; René Spijker; Ann Van den Bruel Journal: Cochrane Database Syst Rev Date: 2020-08-26