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bioRxiv preprint 2 Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly 25 pathogenic influenza present a major threat to public health 1-3 . Despite intense research 26 effort, how, when and where novel diseases appear are still the source of considerable 27 uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, 28 Hubei province, China. At the time of writing, at least 62 suspected cases have been 29 reported since the first patient was hospitalized on December 12 nd 2019. Epidemiological 30 investigation by the local Center for Disease Control and Prevention (CDC) suggested 31 that the outbreak was associated with a sea food market in Wuhan. We studied seven 32 patients who were workers at the market, and collected bronchoalveolar lavage fluid 33 (BALF) from one patient who exhibited a severe respiratory syndrome including fever, 34 dizziness and cough, and who was admitted to Wuhan Central Hospital on December 35 26 th 2019. Next generation metagenomic RNA sequencing 4 identified a novel RNA virus 36 from the family Coronaviridae designed WH-Human-1 coronavirus (WHCV). 37 Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that 38 WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of 39 Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genus Betacoronavirus, 40 subgenus Sarbecovirus) previously sampled from bats in China and that have a history 41 of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-42 over from animals to cause severe disease in humans. 43 44 Seven patients, comprising five men and two women, were hospitalized at the Central 45 : bioRxiv preprint 3 patients was 43, ranging from 31 to 70 years old. The clinical characteristics of the patients 47 are shown in Table 1. Fever and cough were the most common symptoms. All patients had 48 fever with body temperatures ranging from 37.2 o C to 40 o C. Patients 1, 2, 5, 6 and 7 had 49 cough, while patients 1, 2 and 7 presented with severe cough with phlegm at onset of illness. 50 Patients 4 and 5 also complained of chest tightness and dyspnea. Patients 1, 3, 4 and 6 51 experienced dizziness and patient 3 felt weakness. No neurological symptoms were observed 52 in any of the patients. Bacterial culture revealed the presence of Streptococcus bacteria in 53 throat swabs from patients 3, 4 and 7. Combination antibiotic, antiviral and glucocorticoid 54 therapy were administered. Unfortunately, patient 1 and 4 showed respiratory failure: patient 55 1 was given high flow noninvasive ventilation, while patient 4 was provided with nasal/face 56 mask ventilation (Table 1) . Epidemiological investigation by the Wuhan CDC revealed that all the suspected cases 58 were linked to individuals working in a local indoor seafood market. Notably, in addition to 59 fish and shell fish, a variety of live wild animals including hedgehogs, badgers, snakes, and 60 birds (turtledoves) were available for sale in the market before the outbreak began, as well as 61 animal carcasses and animal meat. No bats were available for sale. While the patients might 62 have had contact with wild animals in the market, none recalled exposure to live poultry. Patient 1 was a 41-year-old man with no history of hepatitis, tuberculosis or diabetes. He was admitted and hospitalized in Wuhan Central Hospital 6 days after the onset of illness. The patient reported fever, chest tightness, unproductive cough, pain and weakness for one 66 week on presentation. Physical examination of cardiovascular, abdominal and neurologic 67 examination was normal. Mild lymphopenia (less than 900 cells per cubic milli-meter) was

Complete genome characterisation of a novel coronavirus 4 associated with severe human respiratory disease in Wuhan