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

Figure 1:
Figure 1:
PRISMA flow diagram of the study selection process. CT = computed tomography; PRISMA = Preferred Reporting Items for Systematic Reviews and Metaanalyses; T-PCR = reverse transcriptase-polymerase chain reaction; WHO = World Health Organization.
Figure 2:
Figure 2:
Grouped bar charts for risk of bias and concerns regarding the applicability of the 68 included studies using QUADAS-2. QUADAS-2 = Quality Assessment of Diagnostic Accuracy Studies-2.
Figure 3:
Figure 3:
Forest plots of pooled sensitivity of (a) chest CT and (b) RT-PCR and pooled specificity of (c) chest CT. Univariate analyses were performed for sensitivity and specificity, respectively. CT = computed tomography; RT-PCR = reverse transcriptase-polymerase chain reaction.
Figure 4:
Figure 4:
Estimated positive predictive value and negative predictive value of (a) chest CT and (b) RT-PCR. The solid line indicates the positive predictive value, and the dotted line denotes the negative predictive value. The red dots indicate the predictive values for eight different countries and China (the right-most point; prevalence, 39%). CT = computed tomography; RT-PCR = reverse transcriptase-polymerase chain reaction.
Figure 5:
Figure 5:
Sensitivity analysis for the chest CT using studies with repeated RT-PCR assays as the reference standard. Forest plots of (a) pooled sensitivity and (b) pooled specificity. RTPCR = reverse transcriptase-polymerase chain reaction.
Figure 6:
Figure 6:
Funnel plots. The likelihood of publication bias was low for the studies on chest CT scans and RT-PCR. CT = computed tomography; RT-PCR = reverse transcriptase-polymerase chain reaction.

References

    1. World Health Organization . Coronavirus disease (COVID-19) outbreak. . Accessed March 27, 2020.
    1. World Health Organization . Coronavirus disease (COVID-19) pandemic. . Accessed April 8, 2020.
    1. 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
    1. 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
    1. 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
    1. The Wall Street Journal . Manufacturing defect in some early CDC test kits being probed. . Accessed March 4, 2020.
    1. Chung M, Bernheim A, Mei X, et al. . CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology 2020;295(1):202-207.
    1. STR/ASER COVID-19 position statement. . Accessed March 27, 2020.
    1. Loong TW. Understanding sensitivity and specificity with the right side of the brain. BMJ 2003;327(7417):716-719.
    1. 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.
    1. Chinese Center for Disease Control and Prevention . Specific primers and probes for detection 2019 novel coronavirus. . Accessed March 17, 2020.
    1. 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.
    1. 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.
    1. 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.
    1. 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
    1. 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
    1. 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
    1. 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.
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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.
    1. 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.
    1. 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
    1. 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.
    1. 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
    1. 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
    1. 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
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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
    1. 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.
    1. 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
    1. 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
    1. 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.
    1. 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
    1. 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
    1. Caruso D, Zerunian M, Polici M, et al. . Chest CT features of COVID-19 in Rome, Italy. Radiology 2020. doi: 10.1148/radiol.2020201237
    1. 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.
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. Lu X, Zhang L, Du H, et al. . SARS-CoV-2 infection in children. N Engl J Med 2020. doi: 10.1056/NEJMc2005073
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. Zhang J, Wang S, Xue Y. Fecal specimen diagnosis 2019 novel coronavirus-infected pneumonia. J Med Virol 2020. doi: 10.1002/jmv.25742
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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.
    1. 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.
    1. 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
    1. 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
    1. 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
    1. 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
    1. 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.
    1. 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.
    1. Mulherin SA, Miller WC. Spectrum bias or spectrum effect? Subgroup variation in diagnostic test evaluation. Ann Intern Med 2002;137(7):598-602.
    1. 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.
    1. 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

3
구독하다