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      Chest CT Accuracy in Diagnosing COVID-19 During the Peak of the Italian Epidemic: A Retrospective Correlation with RT-PCR Testing and Analysis of Discordant Cases

      research-article
      a , * , 1 , a , 1 , a , a , a , a , a , a , b , a , a
      European Journal of Radiology
      Elsevier B.V.
      Sars-Cov-2, severe acute respiratory syndrome coronavirus 2, COVID-19, Coronavirus Disease 2019, RT-PCR, real-time reverse-transcriptase-polymerase chain reaction, ED, emergency department, PPV, positive predictive value, NPV, negative predictive value, TP, true positives, FP, false positives, TN, true negatives, FN, false negatives, COPD, chronic obstructive pulmonary disease, CHF, congestive heart failure, COVID-19, Sars-CoV-2, Tomography, X-Ray Computed, Diagnostic X-Ray Radiology

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          Highlights

          • In our experience chest CT had a significantly higher specificity and accuracy in detecting COVID-19 pneumonia than previously reported.

          • Chest CT and RT-PCR positive rates were 485/773 (62.7%) and 462/773 (59.7%), respectively.

          • CT sensitivity, specificity, PPV, NPV, and accuracy for SARS-CoV-2 infection with RT-PCR as reference were 90.7% [95% IC, 87.7% to 93.2%], 78.8% [95% IC, 73.8-83.2%], 86.4% [95% IC, 76.1% - 88.9%], 85.1% [95% IC, 81.0% - 88.4] and 85.9% [95% IC 83.2-88.3%], respectively.

          Abstract

          Objectives

          The goal of this study was to assess chest computed tomography (CT) diagnostic accuracy in clinical practice using RT-PCR as standard of reference.

          Methods

          From March 4th to April 9th 2020, during the peak of the Italian COVID-19 epidemic, we enrolled a series of 773 patients that performed both non-contrast chest CT and RT-PCR with a time interval no longer than a week due to suspected SARS-CoV-2 infection. The diagnostic performance of CT was evaluated according to sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy, considering RT-PCR as the reference standard. An analysis on the patients with discrepant CT scan and RT-PCR result and on the patient with both negative tests was performed.

          Results

          RT-PCR testing showed an overall positive rate of 59.8%. CT sensitivity, specificity, PPV, NPV, and accuracy for SARS-CoV-2 infection were 90.7% [95% IC, 87.7% to 93.2%], 78.8% [95% IC, 73.8-83.2%], 86.4% [95% IC, 76.1% - 88.9%], 85.1% [95% IC, 81.0% - 88.4] and 85.9% [95% IC 83.2-88.3%], respectively. Twenty-five/66 (37.6%) patients with positive CT and negative RT-PCR results and 12/245 (4.9%) patients with both negative tests were nevertheless judged as positive cases by the clinicians based on clinical and epidemiological criteria and consequently treated.

          Conclusions

          In our experience, in a context of high pre-test probability, CT scan shows good sensitivity and a consistently higher specificity for the diagnosis of COVID-19 pneumonia than what reported by previous studies, especially when clinical and epidemiological features are taken into account.

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          Most cited references26

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          Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

          Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.
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            The species Severe acute respiratory syndrome-related coronavirus : classifying 2019-nCoV and naming it SARS-CoV-2

            The present outbreak of a coronavirus-associated acute respiratory disease called coronavirus disease 19 (COVID-19) is the third documented spillover of an animal coronavirus to humans in only two decades that has resulted in a major epidemic. The Coronaviridae Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the classification of viruses and taxon nomenclature of the family Coronaviridae, has assessed the placement of the human pathogen, tentatively named 2019-nCoV, within the Coronaviridae. Based on phylogeny, taxonomy and established practice, the CSG recognizes this virus as forming a sister clade to the prototype human and bat severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus, and designates it as SARS-CoV-2. In order to facilitate communication, the CSG proposes to use the following naming convention for individual isolates: SARS-CoV-2/host/location/isolate/date. While the full spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined, the independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance. This will improve our understanding of virus–host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
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              SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

              To the Editor: The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, and has been declared a public health emergency of international concern by the World Health Organization, may progress to a pandemic associated with substantial morbidity and mortality. SARS-CoV-2 is genetically related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries in 2002–2003. 1 The epidemic of SARS-CoV was successfully contained through public health interventions, including case detection and isolation. Transmission of SARS-CoV occurred mainly after days of illness 2 and was associated with modest viral loads in the respiratory tract early in the illness, with viral loads peaking approximately 10 days after symptom onset. 3 We monitored SARS-CoV-2 viral loads in upper respiratory specimens obtained from 18 patients (9 men and 9 women; median age, 59 years; range, 26 to 76) in Zhuhai, Guangdong, China, including 4 patients with secondary infections (1 of whom never had symptoms) within two family clusters (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The patient who never had symptoms was a close contact of a patient with a known case and was therefore monitored. A total of 72 nasal swabs (sampled from the mid-turbinate and nasopharynx) (Figure 1A) and 72 throat swabs (Figure 1B) were analyzed, with 1 to 9 sequential samples obtained from each patient. Polyester flock swabs were used for all the patients. From January 7 through January 26, 2020, a total of 14 patients who had recently returned from Wuhan and had fever (≥37.3°C) received a diagnosis of Covid-19 (the illness caused by SARS-CoV-2) by means of reverse-transcriptase–polymerase-chain-reaction assay with primers and probes targeting the N and Orf1b genes of SARS-CoV-2; the assay was developed by the Chinese Center for Disease Control and Prevention. Samples were tested at the Guangdong Provincial Center for Disease Control and Prevention. Thirteen of 14 patients with imported cases had evidence of pneumonia on computed tomography (CT). None of them had visited the Huanan Seafood Wholesale Market in Wuhan within 14 days before symptom onset. Patients E, I, and P required admission to intensive care units, whereas the others had mild-to-moderate illness. Secondary infections were detected in close contacts of Patients E, I, and P. Patient E worked in Wuhan and visited his wife (Patient L), mother (Patient D), and a friend (Patient Z) in Zhuhai on January 17. Symptoms developed in Patients L and D on January 20 and January 22, respectively, with viral RNA detected in their nasal and throat swabs soon after symptom onset. Patient Z reported no clinical symptoms, but his nasal swabs (cycle threshold [Ct] values, 22 to 28) and throat swabs (Ct values, 30 to 32) tested positive on days 7, 10, and 11 after contact. A CT scan of Patient Z that was obtained on February 6 was unremarkable. Patients I and P lived in Wuhan and visited their daughter (Patient H) in Zhuhai on January 11 when their symptoms first developed. Fever developed in Patient H on January 17, with viral RNA detected in nasal and throat swabs on day 1 after symptom onset. We analyzed the viral load in nasal and throat swabs obtained from the 17 symptomatic patients in relation to day of onset of any symptoms (Figure 1C). Higher viral loads (inversely related to Ct value) were detected soon after symptom onset, with higher viral loads detected in the nose than in the throat. Our analysis suggests that the viral nucleic acid shedding pattern of patients infected with SARS-CoV-2 resembles that of patients with influenza 4 and appears different from that seen in patients infected with SARS-CoV. 3 The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients. These findings are in concordance with reports that transmission may occur early in the course of infection 5 and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV. How SARS-CoV-2 viral load correlates with culturable virus needs to be determined. Identification of patients with few or no symptoms and with modest levels of detectable viral RNA in the oropharynx for at least 5 days suggests that we need better data to determine transmission dynamics and inform our screening practices.
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                Author and article information

                Contributors
                Journal
                Eur J Radiol
                Eur J Radiol
                European Journal of Radiology
                Elsevier B.V.
                0720-048X
                1872-7727
                25 July 2020
                25 July 2020
                : 109192
                Affiliations
                [a ]Department of Diagnosis and Treatment Services, Radiodiagnostics, Azienda Ospedaliero Universitaria Maggiore della Carità, Novara, Italy
                [b ]Direzione sanitaria, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
                Author notes
                [* ]Corresponding author at: Department of Diagnosis and Treatment Services, Radiodiagnostics, “Azienda Ospedaliero Universitaria Maggiore della Carità”, Corso Mazzini 18, 28100, Novara, Italy. zenofalaschi@ 123456gmail.com
                [1]

                These authors contributed equally to this work.

                Article
                S0720-048X(20)30381-8 109192
                10.1016/j.ejrad.2020.109192
                7382359
                32738464
                6319f9be-8d56-4490-8d57-a48eb03c0d21
                © 2020 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 12 May 2020
                : 4 July 2020
                : 14 July 2020
                Categories
                Article

                Radiology & Imaging
                sars-cov-2, severe acute respiratory syndrome coronavirus 2,covid-19, coronavirus disease 2019,rt-pcr, real-time reverse-transcriptase-polymerase chain reaction,ed, emergency department,ppv, positive predictive value,npv, negative predictive value,tp, true positives,fp, false positives,tn, true negatives,fn, false negatives,copd, chronic obstructive pulmonary disease,chf, congestive heart failure,covid-19,sars-cov-2,tomography,x-ray computed,diagnostic x-ray radiology

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