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      A cross-sectional comparison of epidemiological and clinical features of patients with coronavirus disease (COVID-19) in Wuhan and outside Wuhan, China

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      Travel Medicine and Infectious Disease

      Elsevier Ltd.

      Coronavirus disease 2019, Severe acute respiratory syndrome-related coronavirus 2, Epidemiology, Clinical features, Virulence, Transmission, COVID-19, coronavirus disease 2019, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, CDC, Centre for Disease Control and Prevention, RNA, ribonucleic acid, ICU, intensive care unit, ESR, erythrocyte sedimentation rate, CRP, C-reaction protein, PCT, Procalcitonin, CT, computerized tomography

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          Abstract

          Background

          Coronavirus disease 2019 (COVID-19) has spread outside the initial epicenter of Wuhan. We compared cases in Guangzhou and Wuhan to illustrate potential changes in pathogenicity and epidemiological characteristics as the epidemic has progressed.

          Methods

          We studied 20 patients admitted to the Third Affiliated Hospital of Sun Yat-Sen University in Guangzhou, China from January 22 to February 12, 2020. Data were extracted from medical records. These cases were compared with the 99 cases, previously published in Lancet, from Wuhan Jinyintan Hospital from January 1 to January 20, 2020.

          Results

          Guangzhou patients were younger and had better prognosis than Wuhan patients. The Wuhan patients were more likely to be admitted to the ICU (23% vs 5%) and had a higher mortality rate (11% vs 0%). Cases in Guangzhou tended to be more community clustered. Diarrhea and vomiting were more common among Guangzhou patients and SARS-CoV-2 RNA was found in feces. Fecal SARA-CoV-2 RNA remained positive when nasopharyngeal swabs turned negative in some patients.

          Conclusions

          This study indicates possible diminishing virulence of the virus in the process of transmission. Yet persistent positive RNA in feces after negative nasopharyngeal swabs suggests a possible prolonged transmission period that challenges current quarantine practices.

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          Most cited references 6

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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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            Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications

            Summary Background Since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea was reported on 20th May 2015, there have been 186 confirmed cases, 38 deaths and 16,752 suspected cases. Previously published research on South Korea's MERS outbreak was limited to the early stages, when few data were available. Now that the outbreak has ended, albeit unofficially, a more comprehensive review is appropriate. Methods Data were obtained through the MERS portal by the Ministry for Health and Welfare (MOHW) and Korea Centres for Disease Control and Prevention, press releases by MOHW, and reports by the MERS Policy Committee of the Korean Medical Association. Cases were analysed for general characteristics, exposure source, timeline and infection generation. Sex, age and underlying diseases were analysed for the 38 deaths. Findings Beginning with the index case that infected 28 others, an in-depth analysis was conducted. The average age was 55 years, which was a little higher than the global average of 50 years. As in most other countries, more men than women were affected. The case fatality rate was 19.9%, which was lower than the global rate of 38.7% and the rate in Saudi Arabia (36.5%). In total, 184 patients were infected nosocomially and there were no community-acquired infections. The main underlying diseases were respiratory diseases, cancer and hypertension. The main contributors to the outbreak were late diagnosis, quarantine failure of ‘super spreaders’, familial care-giving and visiting, non-disclosure by patients, poor communication by the South Korean Government, inadequate hospital infection management, and ‘doctor shopping’. The outbreak was entirely nosocomial, and was largely attributable to infection management and policy failures, rather than biomedical factors.
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              Spread of MERS to South Korea and China

              The recent report 1 of the first case of the Middle East respiratory syndrome (MERS) coronavirus infection from Seoul, South Korea, on May 20, 2015, has attracted global media attention. The patient was a man aged 68 years who had travelled to the Middle East (Bahrain, United Arab Emirates, Saudi Arabia, and Qatar) from April 18, to May 3, 2015, and developed symptoms on his return to South Korea on May 11, 2015. This case could have passed unnoticed, since individual cases of MERS have been reported from all continents without major subsequent secondary spread. However, the subsequent major outbreak in Seoul, with 30 MERS cases (two deaths) reported as of June 3, is the largest case cluster of MERS outside the Middle East and a major cause for concern. This outbreak gives us an opportunity to reflect on progress on global efforts being made to control MERS coronavirus since it was first detected in a patient who had died from a severe respiratory illness in June, 2012, in Jeddah, Saudi Arabia. 2 While the source of infection in the index MERS patient during his stay in the Middle East is under investigation, deficiencies in control measures and in prevention of hospital infection in South Korea are most likely to have resulted in the Seoul nosocomial outbreak. This outbreak includes at least 27 secondary cases and two tertiary cases (family members of the index case, other patients who were in the same ward and their family members, and health-care workers who had attended the index patient). Inadequate implementation of a quarantine protocol and poor public health surveillance seem to have allowed a business trip to be made by a symptomatic man aged 44 years, who was in close contact with the index patient, which consisted of travel by air from Seoul to Hong Kong on May 26, 2015, and then by bus from Hong Kong to Huizhou in southern China. He was subsequently confirmed to have MERS coronavirus infection on May 29, 2015, in Huizhou, leading to intensive contact tracing by local public health authorities and panic in the communities in mainland China and Hong Kong. 3 Previous major nosocomial outbreaks of MERS coronavirus infection in Saudi Arabia in April and May, 2013, in Al-Hasa province, 4 and in several Jeddah hospitals in April and May, 2014, 5 were attributed to poor hospital infection control measures and showed no evidence of major viral mutations. The Korean hospital cluster 2 and the export of an active case to China 3 emphasises the importance of maintaining stringent hospital infection control and prevention measures. These measures include isolation of the index patient in a negative-pressure room or a well ventilated room, droplet and contact precaution with eye protection when caring for probable or confirmed cases of MERS coronavirus infection, and airborne precautions when performing aerosol generating procedures. 6 For the hospital infection control and isolation system to function effectively, it is important to maintain administrative controls (such as careful triage of patients, separation of potentially infectious cases from other patients in waiting rooms in the emergency area), environmental controls (such as ensuring a clean environment with adequate ventilation and spatial separation), and compliance with appropriate personal protection equipment (such as gloves, gowns, eye protection, surgical masks, and respirators). 7 MERS had captured global attention and the media spotlight since its discovery in 2012, until it was overshadowed by the epidemic of Ebola virus disease in west Africa. 8 Over the past 3 years, MERS cases have continued to increase and, as of May 31, 2015, 1187 laboratory-confirmed cases have been recorded, with 485 deaths (40% mortality). 9 Although the great majority of MERS cases have been reported in Saudi Arabia and the United Arab Emirates, people with a history of travel to the Middle East have exported cases to Europe, the USA, north Africa, and Asia. Of major concern is that the first case of MERS was reported almost 3 years ago, and yet the disease remains a serious health threat to the global community, with many basic questions remaining unanswered. 10 Phylogenetic analysis of MERS coronavirus isolates from human beings show that camels and bats are reservoirs for MERS coronavirus, but the exact mode of transmission to human beings remains unknown and only a few people infected with MERS have had contact with camels. The absence of such crucial information has made it difficult to develop effective interventions to reduce the risk of disease transmission, define the epidemiology of the disease, and develop effective public health control measures. Importantly, the natural history, risk factors, pathogenesis, viral virulence, viral kinetics, duration of infectiousness, protective immune responses, optimum management, and prognostic factors remain unknown. This information is required for the development and evaluation of new biomarkers, diagnostics, drugs, adjunct therapies, and vaccines.9, 10 Similarly to other coronaviruses, MERS coronavirus is prone to mutations and can acquire an enhanced ability to be transmitted to human beings and between human beings. Such mutations would increase the risk of a pandemic, especially since several million pilgrims travel throughout the year from all continents to Saudi Arabia, with much of this travel associated with the Hajj and Umrah. Fortunately, no increase in MERS cases related to the Hajj has been reported. 11 As with Ebola virus disease, no specific or effective drug treatment or vaccine exists for MERS. Infection prevention and control measures remain crucial to prevent spread of MERS coronavirus during the mass gathering religious events 12 and to avoid secondary outbreaks in contacts. Although Ebola virus disease arose in west Africa and MERS coronavirus in the Middle East, threats of infectious diseases with epidemic potential can arise from any other continent, as witnessed by severe acute respiratory syndrome (SARS), swine-origin influenza A H1N1, and avian influenza A H7N9. The persistence of MERS coronavirus infections in the Middle East and its continuing spread to other countries 3 years after it was first detected points to a global failure by governments and public health systems to adequately assess and respond to such threats. Proper risk assessment and communication procedures necessary to define and control the outbreaks are inadequate, and a coordinated action plan to tackle MERS is sorely needed. With increasing numbers of novel and re-emerging infectious diseases which threaten global health security,13, 14 the time has now come for governments and global public health bodies to show bold leadership by establishing national, regional and pan-continental capacities for rapid conduct of research based on equitable partnerships to generate the best evidence base for formulating effective public health, infection control and treatment interventions 14 required to effectively tackle these infections. © 2015 AMI IMAGES/Science Photo Library 2015 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.
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                Author and article information

                Contributors
                Journal
                Travel Med Infect Dis
                Travel Med Infect Dis
                Travel Medicine and Infectious Disease
                Elsevier Ltd.
                1477-8939
                1873-0442
                9 April 2020
                9 April 2020
                Affiliations
                [a ]Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
                [b ]GuangDong Provincial Key Laboratory of Liver Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
                [c ]Nuffield Department of Women's and Reproductive Health, University of Oxford, UK
                Author notes
                []Corresponding author. Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, China. linbingl@ 123456mail.sysu.edu.cn
                [1]

                Bing-Liang Lin, Jian-Rong He and Zhiliang Gao contributed equally to this work.

                [2]

                Ziying Lei, Huijuan Cao and Yusheng Jie contributed equally to this work.

                Article
                S1477-8939(20)30132-0 101664
                10.1016/j.tmaid.2020.101664
                7194579
                32278758
                © 2020 Elsevier Ltd. 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.

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