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      Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle

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      1 , , 2 , 3 ,
      Journal of Medical Virology
      John Wiley and Sons Inc.

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          Abstract

          Since December 2019, a total of 41 cases of pneumonia of unknown etiology have been confirmed in Wuhan city, Hubei Province, China. Wuhan city is a major transportation hub with a population of more than 11 million people. Most of the patients visited a local fish and wild animal market last month. At a national press conference held today, Dr Jianguo Xu, an academician of the Chinese Academy of Engineering, who led a scientific team announced that a new‐type coronavirus, tentatively named by World Health Organization as the 2019‐new coronavirus (2019‐nCoV), had caused this outbreak. 1 The 2019‐nCoV has a different coronavirus‐specific nucleic acid sequence from known human coronavirus species, which are similar to some of the beta coronaviruses identified in bats. 2 , 3 The virus‐specific nucleic acid sequences were detected in lung fluid, blood and throat swab samples in 15 patients and the virus that was isolated showed a typical coronavirus appearance under electron microscopy. Further research will be conducted to better understand the new coronavirus to develop antiviral agents and vaccines. 4 We applauded the excellent job that has been done so far. The infection was first described in December. Within 9 days, a special team consisted of physicians, scientists and epidemiologists who ruled out several extremely contagious pathogens including SARS, which killed hundreds of people more than a decade ago, and MERS. This has surely alleviated environmental concerns as Hong Kong authorities had quickly stepped up the disinfection of trains and airplanes and checks of passengers due to this outbreak. Most of the patients visited the fish and wild animal market last month in Wuhan. This fish and wild animal market also sold live animals such as poultry, bats, marmots, and snakes. All patients received prompt supportive treatment in quarantine. Among them, seven patients were in serious condition and one patient died. All of the 42 patients so far confirmed were from China except one Thailand patient who was a traveler from Wuhan. Eight patients have been cured of the disease and were discharged from the hospital last week. The 2019‐nCoV now have been isolated from multiple patients and appears to be the culprit. But the mystery has not been completely solved yet. Until there is a formal published scientific manuscript, the facts can be argued, particularly regarding causality despite these facts having been officially announced. The data collected so far is not enough to confirm the causal relationship between the new‐type coronavirus and the respiratory disease based on classical Koch's postulates or modified ones as suggested by Fredricks and Relman. 5 The viral‐specific nucleic acids were only discovered in 15 patients, and successful virus culture was extremely limited to only a few patients. There remains considerable work to be done to differentiate between colonization, shedding, and infection. Additional strains of the 2019‐nCoV need to be isolated to study their homologies. It is expected that antigens and monoclonal antibodies will be developed so serology can be used to confirm previous and acute infection status. The episode demonstrates further the need for rapid and accurate detection and identification methods that can be used in the local hospitals and clinics bearing the burden of identifying and treating patients. Recently, the Clinical Laboratory Improvement Amendments (CLIA) of 1988 has waived highly sensitive and specific molecular devices known as CLIA‐waived devices so that these devices are gradually becoming available for point of care testing. Finally, the epidemiological similarity between this outbreak and that of SARS in 2002‐2003 6 is striking. SARS was then traced to animal markets 7 and eventually to palm civets. 8 Later bats were identified as animal reservoirs. 9 Could this novel coronavirus be originated from wild animals? The family Coronaviridae includes two subfamilies. 10 One, the subfamily Coronavirinae, contains a substantial number of pathogens of mammals that individually cause a remarkable variety of diseases, including pneumonia. In humans, coronaviruses are among the spectrum of viruses that cause the common cold as well as more severe respiratory disease—specifically SARS and MERS, which are both zoonoses. The second subfamily, Torovirinae, contains pathogens of both terrestrial and aquatic animals. The genus Torovirus includes the type species, equine torovirus (Berne virus), which was first isolated from a horse with diarrhea, and the Breda virus, which was first isolated from neonatal calves with diarrhea. White bream virus from fish is the type species of the genus Bafinivirus. However, there is no evidence so far that the seafood from the fish and animal market caused 2019‐nCoV‐associated pneumonia. This epidemiologic similarity clearly provides a starting point for the further investigation of this outbreak. In the meantime, this fish and animal market has been closed until the epidemiological work determines the animal host of this novel coronavirus. Only then will the miracle be complete.

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          Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

          The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society
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            Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China.

            Y Guan (2003)
            A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome (SARS). SCoV-like viruses were isolated from Himalayan palm civets found in a live-animal market in Guangdong, China. Evidence of virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the same market. All the animal isolates retain a 29-nucleotide sequence that is not found in most human isolates. The detection of SCoV-like viruses in small, live wild mammals in a retail market indicates a route of interspecies transmission, although the natural reservoir is not known.
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              Molecular evolution analysis and geographic investigation of severe acute respiratory syndrome coronavirus-like virus in palm civets at an animal market and on farms.

              Massive numbers of palm civets were culled to remove sources for the reemergence of severe acute respiratory syndrome (SARS) in Guangdong Province, China, in January 2004, following SARS coronavirus detection in market animals. The virus was identified in all 91 palm civets and 15 raccoon dogs of animal market origin sampled prior to culling, but not in 1,107 palm civets later sampled at 25 farms, spread over 12 provinces, which were claimed to be the source of traded animals. Twenty-seven novel signature variation residues (SNVs) were identified on the spike gene and were analyzed for their phylogenetic relationships, based on 17 sequences obtained from animals in our study and from other published studies. Analysis indicated that the virus in palm civets at the live-animal market had evolved to infect humans. The evolutionary starting point was a prototype group consisting of three viral sequences of animal origin. Initially, seven SNV sites caused six amino acid changes, at positions 147, 228, 240, 479, 821, and 1080 of the spike protein, to generate low-pathogenicity viruses. One of these was linked to the first SARS patient in the 2003-2004 period. A further 14 SNVs caused 11 amino acid residue changes, at positions 360, 462, 472, 480, 487, 609, 613, 665, 743, 765, and 1163. The resulting high-pathogenicity groups were responsible for infections during the so-called early-phase epidemic of 2003. Finally, the remaining six SNVs caused four amino acid changes, at positions 227, 244, 344, and 778, which resulted in the group of viruses responsible for the global epidemic.
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                Author and article information

                Contributors
                luhongzhou@fudan.edu.cn
                yi-wei.tang@cepheid.com
                Journal
                J Med Virol
                J. Med. Virol
                10.1002/(ISSN)1096-9071
                JMV
                Journal of Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                0146-6615
                1096-9071
                12 February 2020
                April 2020
                : 92
                : 4 , 2019 Novel Coronavirus Origin, Evolution, Disease, Biology and Epidemiology: Part‐I ( doiID: 10.1002/jmv.v92.4 )
                : 401-402
                Affiliations
                [ 1 ] Shanghai Public Health Clinical Center Fudan University Shanghai China
                [ 2 ] Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville Tennessee
                [ 3 ] Cepheid, Danaher Diagnostic Platform Shanghai China
                Author notes
                [*] [* ] Correspondence Hongzhou Lu, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.

                Email: luhongzhou@ 123456fudan.edu.cn (HL)

                Yi‐Wei Tang, Cepheid, Danaher Diagnostic Platform, Shanghai, China.

                Email: yi-wei.tang@ 123456cepheid.com (Y‐WT)

                Author information
                http://orcid.org/0000-0003-4888-6771
                Article
                JMV25678
                10.1002/jmv.25678
                7166628
                31950516
                a79fe1e9-afdd-41af-ae99-007447ca278f
                © 2020 Wiley Periodicals, Inc.

                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.

                History
                : 13 January 2020
                : 15 January 2020
                Page count
                Figures: 0, Tables: 0, Pages: 2, Words: 1116
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                April 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:16.04.2020

                Microbiology & Virology
                Microbiology & Virology

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