Diagnostic Performance of CT and Reverse Transcriptase Polymerase Chain Reaction for Coronavirus Disease 2019: A Meta-Analysis
Hyungjin Kim, Hyunsook Hong, Soon Ho Yoon, Hyungjin Kim, Hyunsook Hong, Soon Ho Yoon
Abstract
Background Recent studies have suggested that chest CT scans could be used as a primary screening or diagnostic tool for coronavirus disease 2019 (COVID-19) in epidemic areas. Purpose To perform a meta-analysis to evaluate diagnostic performance measures, including predictive values of chest CT and initial reverse transcriptase polymerase chain reaction (RT-PCR). Materials and Methods Medline and Embase were searched from January 1, 2020, to April 3, 2020, for studies on COVID-19 that reported the sensitivity, specificity, or both of CT scans, RT-PCR assays, or both. The pooled sensitivity and specificity were estimated by using random-effects models. The actual prevalence (ie, the proportion of confirmed patients among those tested) in eight countries was obtained from web sources, and the predictive values were calculated. Meta-regression was performed to reveal the effect of potential explanatory factors on the diagnostic performance measures. Results The pooled sensitivity was 94% (95% confidence interval [CI]: 91%, 96%; I2 = 95%) for chest CT and 89% (95% CI: 81%, 94%; I2 = 90%) for RT-PCR. The pooled specificity was 37% (95% CI: 26%, 50%; I2 = 83%) for chest CT. The prevalence of COVID-19 outside China ranged from 1.0% to 22.9%. For chest CT scans, the positive predictive value (PPV) ranged from 1.5% to 30.7%, and the negative predictive value (NPV) ranged from 95.4% to 99.8%. For RT-PCR, the PPV ranged from 47.3% to 96.4%, whereas the NPV ranged from 96.8% to 99.9%. The sensitivity of CT was affected by the distribution of disease severity, the proportion of patients with comorbidities, and the proportion of asymptomatic patients (all P < .05). The sensitivity of RT-PCR was negatively associated with the proportion of elderly patients (P = .01). Conclusion Outside of China where there is a low prevalence of coronavirus disease 2019 (range, 1%-22.9%), chest CT screening of patients with suspected disease had low positive predictive value (range, 1.5%-30.7%). © RSNA, 2020 Online supplemental material is available for this article.
Figures
References
- World Health Organization . Coronavirus disease (COVID-19) outbreak. . Accessed March 27, 2020.
- World Health Organization . Coronavirus disease (COVID-19) pandemic. . Accessed April 8, 2020.
- Ai T, Yang Z, Hou H, et al. . Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology 2020. doi: 10.1148/radiol.2020200642
- Fang Y, Zhang H, Xie J, et al. . Sensitivity of chest CT for COVID-19: comparison to RTPCR. Radiology 2020. doi: 10.1148/radiol.2020200432
- Xie X, Zhong Z, Zhao W, Zheng C, Wang F, Liu J. Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR testing. Radiology 2020. doi: 10.1148/radiol.2020200343
- The Wall Street Journal . Manufacturing defect in some early CDC test kits being probed. . Accessed March 4, 2020.
- Chung M, Bernheim A, Mei X, et al. . CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology 2020;295(1):202-207.
- STR/ASER COVID-19 position statement. . Accessed March 27, 2020.
- Loong TW. Understanding sensitivity and specificity with the right side of the brain. BMJ 2003;327(7417):716-719.
- National Administration of Traditional Chinese Medicine . Notice on the issuance of a programme for the diagnosis and treatment of novel coronavirus (2019-nCoV) infected pneumonia (trial fifth edition) . Accessed March 17, 2020.
- Chinese Center for Disease Control and Prevention . Specific primers and probes for detection 2019 novel coronavirus. . Accessed March 17, 2020.
- Diaz M. Performance measures of the bivariate random effects model for meta-analyses of diagnostic accuracy. Comput Stat Data Anal 2015;83(C):82–90.
- Our World in Data Based on the Oxford Martin Programme on Global Development . How many tests for COVID-19 are being performed around the world? . Accessed April 7, 2020.
- Hunter JP, Saratzis A, Sutton AJ, Boucher RH, Sayers RD, Bown MJ. In meta-analyses of proportion studies, funnel plots were found to be an inaccurate method of assessing publication bias. J Clin Epidemiol 2014;67(8):897-903.
- Bai HX, Hsieh B, Xiong Z, et al. . Performance of radiologists in differentiating COVID-19 from viral pneumonia on chest CT. Radiology 2020. doi: 10.1148/radiol.2020200823
- Bernheim A, Mei X, Huang M, et al. . Chest CT findings in coronavirus disease-19 (COVID-19): relationship to duration of infection. Radiology 2020. doi: 10.1148/radiol.2020200463
- Chan JF, Yip CC, To KK, et al. . Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-polymerase chain reaction assay validated in vitro and with clinical specimens. J Clin Microbiol 2020. doi: 10.1128/JCM.00310-20
- Feng K, Yun YX, Wang XF, et al. . Analysis of CT features of 15 children with 2019 novel coronavirus infection. Zhonghua Er Ke Za Zhi 2020;58(0):E007.
- Guan WJ, Ni ZY, Hu Y, et al. . Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020. doi: 10.1056/NEJMoa2002032
- Hu Z, Song C, Xu C, et al. . Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China. Sci China Life Sci 2020. doi: 10.1007/s11427-020-1661-4
- Li K, Wu J, Wu F, et al. . The clinical and chest CT features associated with severe and critical COVID-19 pneumonia. Invest Radiol 2020. doi: 10.1097/RLI.0000000000000672
- Li W, Cui H, Li K, Fang Y, Li S. Chest computed tomography in children with COVID-19 respiratory infection. Pediatr Radiol 2020. doi: 10.1007/s00247-020-04656-7
- Liu K, Fang YY, Deng Y, et al. . Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei province. Chin Med J (Engl) 2020. doi: 10.1097/CM9.0000000000000744
- Liu Y, Yang Y, Zhang C, et al. . Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci 2020;63(3):364-374.
- Shi H, Han X, Jiang N, et al. . Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 2020;20(4):425-434.
- Wang D, Hu B, Hu C, et al. . Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020. doi: 10.1001/jama.2020.1585
- Wang D, Ju XL, Xie F, et al. . Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China. Zhonghua Er Ke Za Zhi 2020;58(4):E011.
- Wang L, Gao YH, Lou LL, Zhang GJ. The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China. Eur Respir J 2020. doi: 10.1183/13993003.00398-2020
- Wu C, Chen X, Cai Y, et al. . Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020. doi: 0.1001/jamainternmed.2020.0994
- Wu J, Liu J, Zhao X, et al. . Clinical characteristics of imported cases of COVID-19 in Jiangsu province: a multicenter descriptive study. Clin Infect Dis 2020. doi: 10.1093/cid/ciaa199
- Xie C, Jiang L, Huang G, et al. . Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests. Int J Infect Dis 2020;93:264-267.
- Xu XW, Wu XX, Jiang XG, et al. . Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ 2020;368:m606.
- Xu YH, Dong JH, An WM, et al. . Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2. J Infect 2020;80(4):394-400.
- Yang W, Cao Q, Qin L, et al. . Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China. J Infect 2020;80(4):388-393.
- Yoon SH, Lee KH, Kim JY, et al. . Chest radiographic and CT findings of the 2019 novel coronavirus disease (COVID-19): analysis of nine patients treated in Korea. Korean J Radiol 2020;21(4):494-500.
- Zhang JJ, Dong X, Cao YY, et al. . Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy 2020. doi: 10.1111/all.14238
- Zhang MQ, Wang XH, Chen YL, et al. . Clinical features of 2019 novel coronavirus pneumonia in the early stage from a fever clinic in Beijing. Zhonghua Jie He He Hu Xi Za Zhi 2020;43(3):215-218.
- Zhao D, Yao F, Wang L, et al. . A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias. Clin Infect Dis 2020. doi: 10.1093/cid/ciaa247
- Zhu W, Xie K, Lu H, Xu L, Zhou S, Fang S. Initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of Hubei, China. J Med Virol 2020. doi: 10.1002/jmv.25763
- Zhu ZW, Tang JJ, Chai XP, et al. . Comparison of heart failure and 2019 novel coronavirus pneumonia in chest CT features and clinical characteristics. Zhonghua Xin Xue Guan Bing Za Zhi 2020;48(0):E007.
- Zhao W, Zhong Z, Xie X, Yu Q, Liu J. Relation between chest CT findings and clinical conditions of coronavirus disease (COVID-19) pneumonia: a multicenter study. AJR Am J Roentgenol 2020. doi: 10.2214/AJR.20.22976
- Agostini A, Floridi C, Borgheresi A, et al. . Proposal of a low-dose, long-pitch, dual-source chest CT protocol on third-generation dual-source CT using a tin filter for spectral shaping at 100 kVp for coronavirus disease 2019 (COVID-19) patients: a feasibility study. Radiol Med 2020. doi: 10.1007/s11547-020-01179-x
- Caruso D, Zerunian M, Polici M, et al. . Chest CT features of COVID-19 in Rome, Italy. Radiology 2020. doi: 10.1148/radiol.2020201237
- Chan JF, Yuan S, Kok KH, et al. . A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020;395(10223):514-523.
- Chen J, Qi T, Liu L, et al. . Clinical progression of patients with COVID-19 in Shanghai, China. J Infect 2020. doi: 10.1016/j.jinf.2020.03.004
- Chen Z, Fan H, Cai J, et al. . High-resolution computed tomography manifestations of COVID-19 infections in patients of different ages. Eur J Radiol 2020. doi: 10.1016/j.ejrad.2020.108972
- Cheng Z, Lu Y, Cao Q, et al. . Clinical features and chest CT manifestations of coronavirus disease 2019 (COVID-19) in a single-center study in Shanghai, China. AJR Am J Roentgenol 2020. doi: 10.2214/AJR.20.22959
- Guan CS, Lv ZB, Yan S, et al. . Imaging features of coronavirus disease 2019 (COVID-19): evaluation on thin-section CT. Acad Radiol 2020. doi: 10.1016/j.acra.2020.03.002
- Han R, Huang L, Jiang H, Dong J, Peng H, Zhang D. Early clinical and CT manifestations of coronavirus disease 2019 (COVID-19) pneumonia. AJR Am J Roentgenol 2020. doi: 10.2214/AJR.20.22961
- Himoto Y, Sakata A, Kirita M, et al. . Diagnostic performance of chest CT to differentiate COVID-19 pneumonia in non-high-epidemic area in Japan. Jpn J Radiol 2020. doi: 10.1007/s11604-020-00958-w
- Huang G, Gong T, Wang G, et al. . Timely diagnosis and treatment shortens the time to resolution of coronavirus disease (COVID-19) pneumonia and lowers the highest and last CT scores from sequential chest CT. AJR Am J Roentgenol 2020. doi: 10.2214/AJR.20.23078
- Iwasawa T, Sato M, Yamaya T, et al. . Ultra-high-resolution computed tomography can demonstrate alveolar collapse in novel coronavirus (COVID-19) pneumonia. Jpn J Radiol 2020. doi: 10.1007/s11604-020-00956-y
- Li C, Ji F, Wang L, et al. . Asymptomatic and human-to-human transmission of SARSCoV-2 in a 2-family cluster, Xuzhou, China. Emerg Infect Dis 2020. doi: 10.3201/eid2607.200718
- Li K, Fang Y, Li W, et al. . CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19). Eur Radiol 2020. doi: 10.1007/s00330-020-06817-6
- Li P, Fu JB, Li KF, et al. . Transmission of COVID-19 in the terminal stage of incubation period: a familial cluster. Int J Infect Dis 2020. doi: 10.1016/j.ijid.2020.03.027
- Ling Z, Xu X, Gan Q, et al. . Asymptomatic SARS-CoV-2 infected patients with persistent negative CT findings. Eur J Radiol 2020. doi: 10.1016/j.ejrad.2020.108956
- Liu K, Chen Y, Lin R, Han K. Clinical features of COVID-19 in elderly patients: a comparison with young and middle-aged patients. J Infect 2020. doi: 10.1016/j.jinf.2020.03.005
- Liu KC, Xu P, Lv WF, et al. . CT manifestations of coronavirus disease-2019: a retrospective analysis of 73 cases by disease severity. Eur J Radiol 2020. doi: 10.1016/j.ejrad.2020.108941
- Liu M, Song Z, Xiao K. High-resolution computed tomography manifestations of 5 pediatric patients with 2019 novel coronavirus. J Comput Assist Tomogr 2020. doi: 10.1097/RCT.0000000000001023
- Long C, Xu H, Shen Q, et al. . Diagnosis of the coronavirus disease (COVID-19): rRTPCR or CT? Eur J Radiol 2020. doi: 10.1016/j.ejrad.2020.108961
- Lu X, Zhang L, Du H, et al. . SARS-CoV-2 infection in children. N Engl J Med 2020. doi: 10.1056/NEJMc2005073
- Qiu H, Wu J, Hong L, Luo Y, Song Q, Chen D. Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. Lancet Infect Dis 2020. doi: doi: 10.1016/S1473-3099(20)30198-5
- Sun Q, Xu X, Xie J, Li J, Huang X. Evolution of computed tomography manifestations in five patients who recovered from coronavirus disease 2019 (COVID-19) pneumonia. Korean J Radiol 2020. doi: 10.3348/kjr.2020.0157
- Wang K, Kang S, Tian R, Zhang X, Zhang X, Wang Y. Imaging manifestations and diagnostic value of chest CT of coronavirus disease 2019 (COVID-19) in the Xiaogan area. Clin Radiol 2020. doi: 10.1016/j.crad.2020.03.004
- Wang Y, Liu Y, Liu L, Wang X, Luo N, Ling L. Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavirus-2 in Shenzhen, China. J Infect Dis 2020. doi: 10.1093/infdis/jiaa119
- Wong HYF, Lam HYS, Fong AH, et al. . Frequency and distribution of chest radiographic findings in COVID-19 positive patients. Radiology 2020. doi: 10.1148/radiol.2020201160
- Xu T, Chen C, Zhu Z, et al. . Clinical features and dynamics of viral load in imported and non-imported patients with COVID-19. Int J Infect Dis 2020. doi: 10.1016/j.ijid.2020.03.022
- Zhang J, Wang S, Xue Y. Fecal specimen diagnosis 2019 novel coronavirus-infected pneumonia. J Med Virol 2020. doi: 10.1002/jmv.25742
- Zhang S, Li H, Huang S, You W, Sun H. High-resolution CT features of 17 cases of corona virus disease 2019 in Sichuan province, China. Eur Respir J 2020. doi: 10.1183/13993003.00334-2020
- Zhao X, Liu B, Yu Y, et al. . The characteristics and clinical value of chest CT images of novel coronavirus pneumonia. Clin Radiol 2020. doi: 10.1016/j.crad.2020.03.002
- Zheng F, Liao C, Fan QH, et al. . Clinical characteristics of children with coronavirus disease 2019 in Hubei, China. Curr Med Sci 2020. doi: 10.1007/s11596-020-2172-6
- Zhou Y, Zhang Z, Tian J, Xiong S. Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. Ann Palliat Med 2020. doi: 10.21037/apm.2020.03.26
- Zhou Z, Guo D, Li C, et al. . Coronavirus disease 2019: initial chest CT findings. Eur Radiol 2020. doi: 10.1007/s00330-020-06816-7
- Inui S, Fujikawa A, Jitsu M, et al. . Chest CT findings in cases from the cruise ship “Diamond Princess” with coronavirus disease 2019 (COVID-19). Radiology: Cardiothoracic Imaging 2020;2(2):e200110.
- Zhang W, Du RH, Li B, et al. . Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect 2020;9(1):386-389.
- Lescure FX, Bouadma L, Nguyen D, et al. . Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis 2020. doi: 10.1016/S1473-3099(20)30200-0
- Li Y, Yao L, Li J, et al. . Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19. J Med Virol 2020. doi: 10.1002/jmv.25786
- Wolfel R, Corman VM, Guggemos W, et al. . Virological assessment of hospitalized patients with COVID-2019. Nature 2020. doi: 10.1038/s41586-020-2196-x
- Young BE, Ong SWX, Kalimuddin S, et al. . Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA 2020. doi: 10.1001/jama.2020.3204
- American College of Radiology . ACR recommendations for the use of chest radiography and computed tomography (CT) for suspected COVID-19 infection. . Accessed March 30, 2020.
- Leeflang MM, Rutjes AW, Reitsma JB, Hooft L, Bossuyt PM. Variation of a test's sensitivity and specificity with disease prevalence. CMAJ 2013;185(11):E537-544.
- Mulherin SA, Miller WC. Spectrum bias or spectrum effect? Subgroup variation in diagnostic test evaluation. Ann Intern Med 2002;137(7):598-602.
- Indian Council of Medical Research . Guidelines for use of commercial kits for nasal/throat swab based diagnosis of COVID-19 in India, 2 April, 2020. . Accessed April 8, 2020.
- Irwig L, Macaskill P, Glasziou P, Fahey M. Meta-analytic methods for diagnostic test accuracy. J Clin Epidemiol 1995;48(1):119-130.
Source: PubMed