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      The COVID‐19 epidemic


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          The current outbreak of the novel coronavirus SARS‐CoV‐2 (coronavirus disease 2019; previously 2019‐nCoV), epi‐centred in Hubei Province of the People’s Republic of China, has spread to many other countries. On 30. January 2020, the WHO Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations. The case detection rate is changing daily and can be tracked in almost real time on the website provided by Johns Hopkins University 1 and other forums. As of midst of February 2020, China bears the large burden of morbidity and mortality, whereas the incidence in other Asian countries, in Europe and North America remains low so far. Coronaviruses are enveloped, positive single‐stranded large RNA viruses that infect humans, but also a wide range of animals. Coronaviruses were first described in 1966 by Tyrell and Bynoe, who cultivated the viruses from patients with common colds 2. Based on their morphology as spherical virions with a core shell and surface projections resembling a solar corona, they were termed coronaviruses (Latin: corona = crown). Four subfamilies, namely alpha‐, beta‐, gamma‐ and delta‐coronaviruses exist. While alpha‐ and beta‐coronaviruses apparently originate from mammals, in particular from bats, gamma‐ and delta‐viruses originate from pigs and birds. The genome size varies between 26 kb and 32 kb. Among the seven subtypes of coronaviruses that can infect humans, the beta‐coronaviruses may cause severe disease and fatalities, whereas alpha‐coronaviruses cause asymptomatic or mildly symptomatic infections. SARS‐CoV‐2 belongs to the B lineage of the beta‐coronaviruses and is closely related to the SARS‐CoV virus 3, 4. The major four structural genes encode the nucleocapsid protein (N), the spike protein (S), a small membrane protein (SM) and the membrane glycoprotein (M) with an additional membrane glycoprotein (HE) occurring in the HCoV‐OC43 and HKU1 beta‐coronaviruses 5. SARS‐CoV‐2 is 96% identical at the whole‐genome level to a bat coronavirus 4. SARS‐CoV‐2 apparently succeeded in making its transition from animals to humans on the Huanan seafood market in Wuhan, China. However, endeavours to identify potential intermediate hosts seem to have been neglected in Wuhan and the exact route of transmission urgently needs to be clarified. The initial clinical sign of the SARS‐CoV‐2‐related disease COVID‐19 which allowed case detection was pneumonia. More recent reports also describe gastrointestinal symptoms and asymptomatic infections, especially among young children 6. Observations so far suggest a mean incubation period of five days 7 and a median incubation period of 3 days (range: 0–24 days) 8. The proportion of individuals infected by SARS‐CoV‐2 who remain asymptomatic throughout the course of infection has not yet been definitely assessed. In symptomatic patients, the clinical manifestations of the disease usually start after less than a week, consisting of fever, cough, nasal congestion, fatigue and other signs of upper respiratory tract infections. The infection can progress to severe disease with dyspnoea and severe chest symptoms corresponding to pneumonia in approximately 75% of patients, as seen by computed tomography on admission 8. Pneumonia mostly occurs in the second or third week of a symptomatic infection. Prominent signs of viral pneumonia include decreased oxygen saturation, blood gas deviations, changes visible through chest X‐rays and other imaging techniques, with ground glass abnormalities, patchy consolidation, alveolar exudates and interlobular involvement, eventually indicating deterioration. Lymphopenia appears to be common, and inflammatory markers (C‐reactive protein and proinflammatory cytokines) are elevated. Recent investigations of 425 confirmed cases demonstrate that the current epidemic may double in the number of affected individuals every seven days and that each patient spreads infection to 2.2 other individuals on average (R0) 6. Estimates from the SARS‐CoV outbreak in 2003 reported an R0 of 3 9. A recent data‐driven analysis from the early phase of the outbreak estimates a mean R0 range from 2.2 to 3.58 10. Dense communities are at particular risk and the most vulnerable region certainly is Africa, due to dense traffic between China and Africa. Very few African countries have sufficient and appropriate diagnostic capacities and obvious challenges exist to handle such outbreaks. Indeed, the virus might soon affect Africa. WHO has identified 13 top‐priority countries (Algeria, Angola, Cote d’Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Kenya, Mauritius, Nigeria, South Africa, Tanzania, Uganda, Zambia) which either maintain direct links to China or a high volume of travel to China. Recent studies indicate that patients ≥60 years of age are at higher risk than children who might be less likely to become infected or, if so, may show milder symptoms or even asymptomatic infection 7. As of 13. February 2020, the case fatality rate of COVID‐19 infections has been approximately 2.2% (1370/60363; 13. February 2020, 06:53 PM CET); it was 9.6% (774/8096) in the SARS‐CoV epidemic 11 and 34.4% (858/2494) in the MERS‐CoV outbreak since 2012 12. Like other viruses, SARS‐CoV‐2 infects lung alveolar epithelial cells using receptor‐mediated endocytosis via the angiotensin‐converting enzyme II (ACE2) as an entry receptor 4. Artificial intelligence predicts that drugs associated with AP2‐associated protein kinase 1 (AAK1) disrupting these proteins may inhibit viral entry into the target cells 13. Baricitinib, used in the treatment of rheumatoid arthritis, is an AAK1 and Janus kinase inhibitor and suggested for controlling viral replication 13. Moreover, one in vitro and a clinical study indicate that remdesivir, an adenosine analogue that acts as a viral protein inhibitor, has improved the condition in one patient 14, 15. Chloroquine, by increasing the endosomal pH required for virus‐cell fusion, has the potential of blocking viral infection 15 and was shown to affect activation of p38 mitogen‐activated protein kinase (MAPK), which is involved in replication of HCoV‐229E 16. A combination of the antiretroviral drugs lopinavir and ritonavir significantly improved the clinical condition of SARS‐CoV patients 17 and might be an option in COVID‐19 infections. Further possibilities include leronlimab, a humanised monoclonal antibody (CCR5 antagonist), and galidesivir, a nucleoside RNA polymerase inhibitor, both of which have shown survival benefits in several deadly virus infections and are being considered as potential treatment candidates 18. Repurposing these available drugs for immediate use in treatment in SARS‐CoV‐2 infections could improve the currently available clinical management. Clinical trials presently registered at ClinicalTrials.gov focus on the efficacy of remdesivir, immunoglobulins, arbidol hydrochloride combined with interferon atomisation, ASC09F+Oseltamivir, ritonavir plus oseltamivir, lopinavir plus ritonavir, mesenchymal stem cell treatment, darunavir plus cobicistat, hydroxychloroquine, methylprednisolone and washed microbiota transplantation 19. Given the fragile health systems in most sub‐Saharan African countries, new and re‐emerging disease outbreaks such as the current COVID‐19 epidemic can potentially paralyse health systems at the expense of primary healthcare requirements. The impact of the Ebola epidemic on the economy and healthcare structures is still felt five years later in those countries which were affected. Effective outbreak responses and preparedness during emergencies of such magnitude are challenging across African and other lower‐middle‐income countries. Such situations can partly only be mitigated by supporting existing regional and sub‐Saharan African health structures.

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          Is Open Access

          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

            Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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              A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster

              Summary Background An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. Methods In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. Findings From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6–10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. Interpretation Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. Funding The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).

                Author and article information

                Trop Med Int Health
                Trop. Med. Int. Health
                Tropical Medicine & International Health
                John Wiley and Sons Inc. (Hoboken )
                16 February 2020
                March 2020
                : 25
                : 3 ( doiID: 10.1111/tmi.v25.3 )
                : 278-280
                [ 1 ] Institute of Tropical Medicine Universitätsklinikum Tübingen Germany
                [ 2 ] Vietnamese German Center for Medical Research Hanoi Vietnam
                [ 3 ] Faculty of Medicine Duy Tan University Da Nang Vietnam
                Author notes
                [*] [* ] Corresponding Author Thirumalaisamy P. Velavan, Institute of Tropical Medicine, Wilhelmstr 27, 72074 Tübingen, Germany. E‐mail: velavan@ 123456medizin.uni-tuebingen.de


                Both authors contributed equally. TPV is a member of the Pan African Network for Rapid Research, Response, and Preparedness for Infectious Diseases Epidemics consortium (PANDORA‐ID‐NET; RIA2016E‐1609).

                © 2020 John Wiley & Sons Ltd

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                Page count
                Figures: 0, Tables: 0, Pages: 3, Words: 1660
                Custom metadata
                March 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                covid‐19, epidemic, sars‐cov2, wuhan, 2019‐ncov


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