s u m m a r y Results: Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2-7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12-20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8-11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P < 0.0 0 01). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10-12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU ( P < 0.0 0 01). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. Conclusions: The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.

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In the Acknowledgements section of this Article, the grant number 'SQ2019FY010009' should have been '2019FY101500'; this has been corrected online.

COVID‐19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID‐19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID‐19‐infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue‐specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN‐I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID‐19‐infected patients experiencing milder disease symptoms showed robust T‐cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS‐CoV‐2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID‐19.

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). 57Epidemiological 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 th...