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      Coronavirus Disease 2019: Initial Detection on Chest CT in a Retrospective Multicenter Study of 103 Chinese Subjects

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          Abstract

          Background

          Coronavirus disease 2019 (COVID-19) is a new viral respiratory disease that has recently emerged from China, becoming a pandemic. However, few studies have analyzed data regarding the clinical performance of chest computed tomography (CT) obtained in subjects with suspected COVID-19 at the initial presentation to medical facilities.

          Objective

          The purpose of the present study was to evaluate the performance of chest CT the initial presentation of patients with suspected COVID-19.

          Methods

          Data from 103 patients who were under investigation for COVID-19 based on inclusion criteria according to WHO Interim Guidance were retrospectively collected from January 21, 2020 to February 14, 2020. All patients underwent chest CT scanning and reverse transcription polymerase chain reaction testing (RT-PCR) for COVID-19 at hospital presentation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) (with 95% confidence intervals) were calculated to evaluate the performance of CT. Subgroup analyses were also performed based on the geographical distribution of these cases in the province of Henan, China.

          Results

          There were 88 /103 (85%) patients with COVID-19 confirmed by RT-PCR. The overall sensitivity, specificity, PPV, and NPV were 93% (85-97%), 53% (27-77%), 92% (83-96%), and 42% (18-70%), respectively. Similar results were shown in both geographic regions. The respective sensitivity, specificity, PPV, and NPV for chest CT in the districts of Xinyang and Zhumadian (n = 56) were 92% (80-97%), 63% (26-90%), 93% (81-98%), and 56% (23-85%), while these indicators in the district of Anyang (n = 47) were 95% (81-99%), 43% (12-80%), 90% (76-97%), and 60% (17-93%). There were no significant differences in the prevalence of positive exams in the two geographic subgroups for CT ( P=0.423) or RT-PCR ( P=0.931).

          Conclusion

          Although initial chest CT obtained at hospital presentation showed high sensitivity in patients under investigation for COVID-19 in the two geographic regions in Henan province, the NPV was only modest, suggesting low value of CT as a screening tool.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

            Background Chest CT is used for diagnosis of 2019 novel coronavirus disease (COVID-19), as an important complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests. Purpose To investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19. Methods From January 6 to February 6, 2020, 1014 patients in Wuhan, China who underwent both chest CT and RT-PCR tests were included. With RT-PCR as reference standard, the performance of chest CT in diagnosing COVID-19 was assessed. Besides, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative, respectively) was analyzed as compared with serial chest CT scans for those with time-interval of 4 days or more. Results Of 1014 patients, 59% (601/1014) had positive RT-PCR results, and 88% (888/1014) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95%CI, 95-98%, 580/601 patients) based on positive RT-PCR results. In patients with negative RT-PCR results, 75% (308/413) had positive chest CT findings; of 308, 48% were considered as highly likely cases, with 33% as probable cases. By analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was 5.1 ± 1.5 days; the initial positive to subsequent negative RT-PCR result was 6.9 ± 2.3 days). 60% to 93% of cases had initial positive CT consistent with COVID-19 prior (or parallel) to the initial positive RT-PCR results. 42% (24/57) cases showed improvement in follow-up chest CT scans before the RT-PCR results turning negative. Conclusion Chest CT has a high sensitivity for diagnosis of COVID-19. Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas. A translation of this abstract in Farsi is available in the supplement. - ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.
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              The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China

              The city of Wuhan in China is the focus of global attention due to an outbreak of a febrile respiratory illness due to a coronavirus 2019-nCoV. In December 2019, there was an outbreak of pneumonia of unknown cause in Wuhan, Hubei province in China, with an epidemiological link to the Huanan Seafood Wholesale Market where there was also sale of live animals. Notification of the WHO on 31 Dec 2019 by the Chinese Health Authorities has prompted health authorities in Hong Kong, Macau, and Taiwan to step up border surveillance, and generated concern and fears that it could mark the emergence of a novel and serious threat to public health (WHO, 2020a, Parr, 2020). The Chinese health authorities have taken prompt public health measures including intensive surveillance, epidemiological investigations, and closure of the market on 1 Jan 2020. SARS-CoV, MERS-CoV, avian influenza, influenza and other common respiratory viruses were ruled out. The Chinese scientists were able to isolate a 2019-nCoV from a patient within a short time on 7 Jan 2020 and perform genome sequencing of the 2019-nCoV. The genetic sequence of the 2019-nCoV has become available to the WHO on 12 Jan 2020 and this has facilitated the laboratories in different countries to produce specific diagnostic PCR tests for detecting the novel infection (WHO, 2020b). The 2019-nCoV is a β CoV of group 2B with at least 70% similarity in genetic sequence to SARS-CoV and has been named 2019-nCoV by the WHO. SARS is a zoonosis caused by SARS-CoV, which first emerged in China in 2002 before spreading to 29 countries/regions in 2003 through a travel-related global outbreak with 8,098 cases with a case fatality rate of 9.6%. Nosocomial transmission of SARS-CoV was common while the primary reservoir was putatively bats, although unproven as the actual source and the intermediary source was civet cats in the wet markets in Guangdong (Hui and Zumla, 2019). MERS is a novel lethal zoonotic disease of humans endemic to the Middle East, caused by MERS-CoV. Humans are thought to acquire MERS-CoV infection though contact with camels or camel products with a case fatality rate close to 35% while nosocomial transmission is also a hallmark (Azhar et al., 2019). The recent outbreak of clusters of viral pneumonia due to a 2019-nCoV in the Wuhan market poses significant threats to international health and may be related to sale of bush meat derived from wild or captive sources at the seafood market. As of 10 Jan 2020, 41 patients have been diagnosed to have infection by the 2019-nCoV animals. The onset of illness of the 41 cases ranges from 8 December 2019 to 2 January 2020. Symptoms include fever (>90% cases), malaise, dry cough (80%), shortness of breath (20%) and respiratory distress (15%). The vital signs were stable in most of the cases while leucopenia and lymphopenia were common. Among the 41 cases, six patients have been discharged, seven patients are in critical care and one died, while the remaining patients are in stable condition. The fatal case involved a 61 year-old man with an abdominal tumour and cirrhosis who was admitted to a hospital due to respiratory failure and severe pneumonia. The diagnoses included severe pneumonia, acute respiratory distress syndrome, septic shock and multi-organ failure. The 2019-nCoV infection in Wuhan appears clinically milder than SARS or MERS overall in terms of severity, case fatality rate and transmissibility, which increases the risk of cases remaining undetected. There is currently no clear evidence of human to human transmission. At present, 739 close contacts including 419 healthcare workers are being quarantined and monitored for any development of symptoms (WHO, 2020b, Center for Health Protection and HKSAR, 2020). No new cases have been detected in Wuhan since 3 January 2020. However the first case outside China was reported on 13th January 2020 in a Chinese tourist in Thailand with no epidemiological linkage to the Huanan Seafood Wholesale Market. The Chinese Health Authorities have carried out very appropriate and prompt response measures including active case finding, and retrospective investigations of the current cluster of patients which have been completed; The Huanan Seafood Wholesale Market has been temporarily closed to carry out investigation, environmental sanitation and disinfection; Public risk communication activities have been carried out to improve public awareness and adoption of self-protection measures. Technical guidance on novel coronavirus has been developed and will continue to be updated as additional information becomes available. However, many questions about the new coronavirus remain. While it appears to be transmitted to humans via animals, the specific animals and other reservoirs need to be identified, the transmission route, the incubation period and characteristics of the susceptible population and survival rates. At present, there is however very limited clinical information of the 2019-nCoV infection and data are missing in regard to the age range, animal source of the virus, incubation period, epidemic curve, viral kinetics, transmission route, pathogenesis, autopsy findings and any treatment response to antivirals among the severe cases. Once there is any clue to the source of animals being responsible for this outbreak, global public health authorities should examine the trading route and source of movement of animals or products taken from the wild or captive conditions from other parts to Wuhan and consider appropriate trading restrictions or other control measures to limit. The rapid identification and containment of a novel coronavirus virus in a short period of time is a re-assuring and a commendable achievement by China’s public health authorities and reflects the increasing global capacity to detect, identify, define and contain new outbreaks. The latest analysis show that the Wuhan CoV cluster with the SARS CoV.10 (Novel coronavirus - China (01): (HU) WHO, phylogenetic tree Archive Number: 20200112.6885385). This outbreak brings back memories of the novel coronavirus outbreak in China, the severe acute respiratory syndrome (SARS) in China in 2003, caused by a novel SARS-CoV-coronavirus (World Health Organization, 2019a). SARS-CoV rapidly spread from southern China in 2003 and infected more than 3000 people, killing 774 by 2004, and then disappeared – never to be seen again. However, The Middle East Respiratory Syndrome (MERS) Coronavirus (MERS-CoV) (World Health Organization, 2019b), a lethal zoonotic pathogen that was first identified in humans in the Kingdom of Saudi Arabia (KSA) in 2012 continues to emerge and re-emerge through intermittent sporadic cases, community clusters and nosocomial outbreaks. Between 2012 and December 2019, a total of 2465 laboratory-confirmed cases of MERS-CoV infection, including 850 deaths (34.4% mortality) were reported from 27 countries to WHO, the majority of which were reported by KSA (2073 cases, 772 deaths. Whilst several important aspects of MERS-CoV epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, have been defined, there remain many unanswered questions, including source, transmission and epidemic potential. The Wuhan outbreak is a stark reminder of the continuing threat of zoonotic diseases to global health security. More significant and better targeted investments are required for a more concerted and collaborative global effort, learning from experiences from all geographical regions, through a ‘ONE-HUMAN-ENIVRONMENTAL-ANIMAL-HEALTH’ global consortium to reduce the global threat of zoonotic diseases (Zumla et al., 2016). Sharing experience and learning from all geographical regions and across disciplines will be key to sustaining and further developing the progress being made. Author declarations All authors have a specialist interest in emerging and re-emerging pathogens. FN, RK, OD, GI, TDMc, CD and AZ are members of the Pan-African Network on Emerging and Re-emerging Infections (PANDORA-ID-NET) funded by the European and Developing Countries Clinical Trials Partnership the EU Horizon 2020 Framework Programme for Research and Innovation. AZ is a National Institutes of Health Research senior investigator. All authors declare no conflicts of interest.
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                Author and article information

                Contributors
                Journal
                Radiol Cardiothorac Imaging
                Radiol Cardiothorac Imaging
                cardiothoracic
                Radiology. Cardiothoracic Imaging
                Radiological Society of North America
                2638-6135
                06 April 2020
                : 2
                : 2
                : e200092
                Affiliations
                [1]Department of Radiology, The First Affiliated Hospital of Henan University of CM, Zhengzhou 450000, Henan Province, China (Z.W., J.C., L.C., D.W.); Department of Radiology, The Fifth Hospital of Anyang, Anyang 455000, Henan Province, China (Y.C.); Department of Radiology, Zhumadian Central Hospital, Zhumadian 463000, Henan Province, China (L.Z.); GE Healthcare, Shanghai, 201203, China (H.L.); Department of Radiology, XinYang Central Hospital, Xinyang 464000, Henan Province, China (K.D.); Department of Radiology, Xinxian People's Hospital, Xinxin 465550, Henan Province, China (Z.L.)
                Author notes
                Address correspondence to D.W. (e-mail: wangdaoqing1215@ 123456126.com )
                Author information
                https://orcid.org/0000-0002-0270-6694
                https://orcid.org/0000-0002-0136-4143
                https://orcid.org/0000-0003-3769-6016
                https://orcid.org/0000-0003-2111-5985
                https://orcid.org/0000-0003-3194-9895
                https://orcid.org/0000-0002-0551-2051
                https://orcid.org/0000-0002-8445-7766
                https://orcid.org/0000-0003-0032-7575
                Article
                200092
                10.1148/ryct.2020200092
                7194021
                fadbc137-8bb7-47ed-a859-e9b8b1b95a23
                2020 by the Radiological Society of North America, Inc.

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