BMJ

Confidential: For Review Only Clinical findings of second-generation patients with 2019 novel coronavirus: a multicenter, retrospective, observational study

Journal: BMJ

Manuscript ID BMJ-2020-054741

Article Type: Research

BMJ Journal: BMJ

Date Submitted by the 31-Jan-2020 Author:

Complete List of Authors: , - ; University First Affiliated Hospital State Key Laboratory for Diagnosis and Treatment of Infectious Diseases , Xiao-Xin ; First Affiliated Hospital State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Jiang, Xian-Gao; Medical College Ding- Clinical College Xu, Kai-Jin ; Zhejiang University First Affiliated Hospital State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Ying, Ling-Jun ; Ma, Chun-Lian; First People's Hospital of Li, Shi-Bo ; Zhejiang University Hospital Wang, Hua-Ying ; University Medical School Zhang, Sheng ; Taizhou Hospital of Zhejiang Province Gao, Hainv; Zhejiang Shuren University Sheng, -Fang ; Zhejiang University First Affiliated Hospital State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Cai, -Liu ; Zhejiang University First Affiliated Hospital State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Qiu, Yun-Qing ; Zhejiang University First Affiliated Hospital State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Li, Lanjuan; Zhejiang University First Affiliated Hospital State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

2019-novel coronavirus, clinical characteristics, human transmission, Keywords: second-generation patients

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1 2 3 4 1 Clinical findings of second-generation patients with 2019 novel coronavirus: a 5 6 7 2 multicenter, retrospective, observational study 8 9 3 Xiao-Wei Xu 1#, Xiao-Xin Wu1#, Xian-Gao Jiang2, Kai-Jin Xu1, Ling-Jun Ying3, Chun-Lian 10 11 12 4 Ma4, Shi-BoConfidential: Li5, Hua-Ying Wang6, Sheng For Zhang 7Review, Hai-Nv Gao8, Ji-Fang Only Sheng1, Hong-Liu 13 14 5 Cai1, Yun-Qing Qiu1, Lan-Juan Li1* 15 16 17 6 1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National 18 19 20 7 Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for 21 22 8 Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang 23 24 25 9 University, 310003, . 26 27 10 2. Department of Infectious Disease, Wenzhou Sixth People's Hospital, Wenzhou Medical 28 29 30 11 College Dingli Clinical College, Wenzhou, Zhejiang Province, 325000, China. 31 32 33 12 3. Department of Infectious Disease, Taizhou Enze Medical Center(Group) Enze Hospital, 34 35 13 Taizhou University, Taizhou, Zhejiang Province, 318050, China. 36 37 38 14 4. Department of Infectious Disease, First People's Hospital of Wenling, WenLing, Zhejiang 39 40 15 Province, 317500, China. 41 42 43 16 5. Department of Infectious Disease, Zhejiang University ZhouShan Hospital, ZhouShan, 44 45 46 17 Zhejiang Province 316004, China. 47 48 18 6. Department of Respiratory and Critical Care Medicine, Yinzhou People’s Hospital, 49 50 51 19 Affiliated Yinzhou Hospital, College of Medicine, , 251 East Baizhang 52 53 20 Road, Ningbo City, Zhejiang Province, 315040, China 54 55 56 21 7. Department of Infectious Disease, TaiZhou Hospital, Taizhou, Zhejiang Province, 317000, 57 58 59 22 China. 60 1

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1 2 3 4 23 8. Department of Infectious Disease, ShuLan（Hangzhou) Hospital affiliated to Zhejiang 5 6 7 24 Shuren University Shulan International Medical College, Hangzhou 310000, China 8 9 25 10 11 12 26 # Xiao-WeiConfidential: Xu and Xiao-Xin Wu contributed For equally Review to this article. Only 13 14 27 15 16 17 28 *Corresponding author: Lan-Juan Li 18 19 20 29 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical 21 22 30 Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and 23 24 25 31 Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University, 26 27 32 Hangzhou 310003, China. Telephone: +8613906514210; Fax: +86 -571-87236459; Email 28 29 30 33 address: [email protected] 31 32 33 34 34 35 35 36 37 36 38 39 40 37 41 42 38 43 44 39 45 46 47 40 48 49 41 50 51 42 52 53 54 43 55 56 44 57 58 45 59 60 2

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1 2 3 4 46 Abstract: 5 6 7 47 Objective: To study the clinical characteristics of the imported 2019-novel coronavirus 8 9 48 patients in Zhejiang Province. 10 11 12 49 Design: Confidential:Multicenter, retrospective, observational For studyReview Only 13 14 50 Setting: The study covering eight hospitals which located in the different part of Zhejiang 15 16 17 51 province. 18 19 20 52 Participants: Since January 2020, we collected data of 62 patients with laboratory-confirmed 21 22 53 2019-nCoV in designated hospitals of Zhejiang province. 23 24 25 54 Main outcome measures: We used a standardized case-report form to collect clinical data. If 26 27 55 information was not clear, the working group in Hangzhou contacted the physician 28 29 30 56 responsible for the treatment of the patient for clarification. 31 32 33 57 Results: Of the 62 patients studied, only one patient was admitted to the intensive care unit 34 35 58 (ICU), no patient died until the submission time. According to our research, none of the 36 37 38 59 infection cases in Zhejiang had ever been exposed to the Huanan seafood marker, all the 39 40 60 patients were infected by human transmission. The most common symptoms at onset of 41 42 43 61 illness were fever (48 [77.4 %]), cough (50 [80.6%]), expectoration (35 [56.5%]), headache 44 45 46 62 (21 [33.9%]), myalgia or fatigue (32 [51.6%]), diarrhoea (3 [8.1%]), and hemoptysis (2 47 48 63 [3.2%]). Rare of patients (2 [3.2%]) developed shortness of breath. The median time from 49 50 51 64 exposure to infections to illness onset was 4 days (IQR: 3-5 days), from onset of symptoms to 52 53 65 first hospital admission was 2 days (IQR: 1-4.3 days). 54 55 56 66 Conclusions: The 2019-nCoV could be easily transmitted from human to human. At present, 57 58 59 67 the symptoms of secondary infection patients are relatively mild. 60 3

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1 2 3 4 68 Introduction 5 6 7 69 In December, 2019, a group of patients with pneumonia of unknown reason were confirmed 8 9 70 to be infected with 2019 novel coronavirus (2019-nCoV) in , , China, which had 10 11 12 71 not beenConfidential: detected in humans and animals For before.1 ReviewEpidemiological evidence Only suggested that 13 14 72 most of those patients had been presented in a local seafood market in Wuhan2 and the virus 15 16 17 73 gene sequence of patients was highly similar to that of bats and snakes.3,4 The viral 18 19 20 74 2019-nCoV was a kind of coronavirus that was very similar to the severe acute respiratory 21 22 75 syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus 23 24 25 76 (MERS-CoV) which had caused more than 10000 cases and 1632 deaths across the globe.5-7 26 27 77 Some researchers found that the 2019-nCoV has good affinity to human respiratory receptor,8 28 29 30 78 which indicated that 2019-nCoV may have the potential to pose a global public health threat. 31 32 33 79 At the beginning, nearly all of the patients were related to the Huanan seafood market 34 35 80 and the cases were concentrated in Wuhan.9 Global attention was soon attracted on the 36 37 38 81 situation because of the increasing number of new cases.2 The new type of coronavirus 39 40 82 infection is mainly transmitted from animals to humans, and by January 2020, the main 41 42 43 83 infection cases was suspected to be transmitted from human to human.10 Since January 2020, 44 45 46 84 the spread of 2019-nCoV starts to escalate at an alarming rate and the virus quickly expand to 47 48 85 most parts of China and even other countries. Up to 25 January 2020, there were a total of 49 50 51 86 1320 confirmed cases, including 1297 cases from China and 23 oversea cases from 9 52 53 87 countries.11 These figures update every day and are expected to increase in the further. 54 55 56 88 Despite the increasing number of confirmed cases, the clinical investigation of patients 57 58 59 89 was still limited in the literature. A previous study has reported the clinical characteristics of 60 4

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1 2 3 4 90 initial 41 patients in Wuhan area, which contributes to our epidemiological, clinical, 5 6 7 91 laboratory, and radiological characteristics and treatment and clinical outcomes of those 8 9 92 initial patients.9 Another study conducted by Chan et al. revealed a familial cluster of 10 11 12 93 2019-nCoVConfidential: and clearly suggested person-to-person For Review transmission in familyOnly homes or hospital, 13 14 94 and intercity spread of this novel coronavirus are possible.10 At present, as large number of 15 16 17 95 people were returning home from Wuhan during the Chinese Lunar New Year travel rush, 18 19 20 96 more second-generation or later-generations cases are expected to emerge all over the country 21 22 97 and even all over the world. We found that the characteristics of the imported patients were 23 24 25 98 different from those initial patients in Wuhan reported by Bin Cao.10 It is very important to 26 27 99 study the clinical characteristics of the imported patients in Zhejiang Province. 28 29 30 100 Through the analysis of the characteristics of these people, we aim to provide the 31 32 33 101 experiences for prevention and treatment of new coronavirus infection all over the country 34 35 102 and abroad. In this article, we described clinical characteristics and laboratory abnormalities 36 37 38 103 in 62 cases of second generation patients infected with 2019 novel coronavirus in Zhejiang, 39 40 104 China. 41 42 43 105 44 45 46 106 Method 47 48 107 Data sources 49 50 51 108 We conducted a retrospective study focusing on the clinical characteristics of confirmed 52 53 109 cases of the 2019-nCoV infection in Zhejiang Province. All suspected cases with fever and 54 55 56 110 dry cough, especial those with travel history to Wuhan or history of exposure to infected 57 58 59 111 person within 2 weeks before the onset of illness, were transferred to designated hospitals 60 5

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1 2 3 4 112 since January, 2020. The case definitions of confirmed human infection with the 2019-nCoV 5 6 1 7 113 have been described by Zhu et al. Only patients with laboratory-confirmed infection were 8 9 114 enrolled in this study. 10 11 12 115 TheConfidential: medical records of patients were For extracted Review and sent to the Onlydata-collection center in 13 14 116 Hangzhou. A team of physicians who had been taking care of patients with 2019-nCoV 15 16 17 117 infection collected and reviewed the data. This study was approved by the Ethics Committee 18 19 20 118 of the First Affiliated Hospital, Zhejiang University School of Medicine. Because of the 21 22 119 urgent need to collect data on this emerging pathogen, the requirement for informed consent 23 24 25 120 was waived. We used a standardized case-report form to collect clinical data. If information 26 27 121 was not clear, the working group in Hangzhou contacted the physician responsible for the 28 29 30 122 treatment of the patient for clarification. 31 32 33 123 34 35 124 Laboratory confirmation and treatment 36 37 38 125 Laboratory confirmation of the 2019-nCoV was performed with real-time PCR described by 39 40 126 Huang et al.9 The virus detection was repeated for two times with 24 hours apart. 41 42 43 127 . Basic tests were conducted including complete blood count, serum biochemical test and 44 45 46 128 so on. Most of patients received anti-virus treatment including interferon beta-1b inhalation 47 48 129 (5MU/bid) or Lopina veletonavir (400mg/100mg bid). When the resting respiratory rate of 49 50 51 130 patient is more than 30 times per minute at rest, or the oxygen saturation of the patient is 52 53 131 below 93% without oxygen, or the multiple pulmonary lobes of patients were involved with 54 55 56 132 more than 50% progress in 48 hours, the corticosteroid therapy and gamma globulin therapy 57 58 59 133 were given to the patients. The probiotics therapy was performed in most cases. Antibiotics 60 6

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1 2 3 4 134 (oral and intravenous) were administered if the fever lasted longer than 7 days or CRP ≥ 30. 5 6 7 135 Suspected patients have no access to hospital discharge or discontinuation of isolation until 8 9 136 2019-nCoV clearance. 10 11 12 137 Confidential: For Review Only 13 14 138 Statistical analysis 15 16 17 139 Since Huang et al.9 have shown that patients would get worse on the 10th day after onset, we 18 19 20 140 compared the whole cohort with the ones with the course of longer than 10 days. Continuous 21 22 141 variables were summarized as either means and standard deviations or medians with 23 24 25 142 interquartile ranges. For categorical variables, the percentages of patients in each category 26 27 143 were calculated. All analyses were done with SPSS software, version 22.0 28 29 30 144 31 32 33 145 Results 34 35 146 Epidemiologic characteristics 36 37 38 147 By Jan 23, 2020, the clinical data of 62 patients identified as laboratory-confirmed 39 40 148 2019-nCoV infection were collected in Zhejiang. Twenty-five (40.3%) of the 41 42 43 149 2019-nCoV-infected patients were aged 19-40 years, and 33 (53.2%) were aged 41-65 years, 44 45 46 150 2 (3.2%) were children and 2 (3.2%) were elderly. The median age of the patients was 41 47 48 151 years (IQR 32–52; table 1). In our cohort of the 62 patients as of January 23, more than half 49 50 51 152 of the infected patients were men (36 [58.1%]); no patients had a history of Huanan seafood 52 53 153 market exposure, all patients (62/62) had exposure to confirmed 2019-nCoV infected patients. 54 55 56 154 Among 62 patients, 23(37.1%) patients had long term residence in Wuhan. Other 39(62.9%) 57 58 59 155 patients had short term trip to Wuhan before onset. These patients who had short term trip to 60 7

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1 2 3 4 156 Wuhan were concluded to calculate the incubation period. At the same time, we selected the 5 6 7 157 patients (n=33) with course longer than 10 days. Among these patients, 10 (30.3%) of the 8 9 158 2019-nCoV-infected patients were aged 19-40 years, and 22 (66.7%) were aged 41-65 years, 10 11 12 159 and 1 (3%)Confidential: were elderly. The median age For of the patients Review was 45 years Only (IQR 37–54.5; table 1). 13 14 160 15 16 17 161 Clinical features 18 19 20 162 Among the group of 62 patients, one third of patients had underlying diseases (20 [32.3%]), 21 22 163 including liver disease (7 [11.3%]), hypertension (5 [8.1%]), chronic obstructive pulmonary 23 24 25 164 disease diabetes (1 [1.6%]), renal diseases (1 [1.6%]) and cardiovascular disease (1 [1.6%]). 26 27 165 More than one third were found to be associated with familial clusters (21 [33.9%]). At the 28 29 30 166 same time, we selected the patients (n=33) with course longer than 10 days. More than one 31 32 33 167 third patients had underlying diseases (13 [39.4%]), including liver disease (4 [12.1%]), 34 35 168 hypertension (4 [12.1%]), chronic obstructive pulmonary disease diabetes (1 [3%]), and 36 37 38 169 cardiovascular disease (1 [1.6%]). Less than one third were found to be associated with 39 40 170 familial clusters (21 [33.9%]). 41 42 43 171 Among the group of 62 patients, we found that the median time of incubation period 44 45 46 172 from exposure was 4 days (IQR 3-5). The median time from onset of symptoms to first 47 48 173 hospital admission was 2 days (IQR 1-4.3). The most common symptoms at onset of illness 49 50 51 174 were fever (48 [77.4 %]), cough (50 [80.6%]), expectoration (35 [56.5%]), headache (21 52 53 175 [33.9%]), myalgia or fatigue (32 [51.6%]), diarrhoea (3 [8.1%]), and hemoptysis (2 [3.2%]). 54 55 56 176 Only 2 patients (2 [3.2%]) developed shortness of breath. Among those patients who have 57 58 59 177 disease course over 10 days. We found that the median time of incubation period from 60 8

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1 2 3 4 178 exposure was 3 days (IQR 3-4). The median time from onset of symptoms to first hospital 5 6 7 179 admission was 6.5 days (IQR 5.0-9.0). The most common symptoms at onset of illness were 8 9 180 cough (27 [81.8 %]), fever (26 [78.8%]), expectoration (19 [57.6%]), myalgia or fatigue (19 10 11 12 181 [57.6%])Confidential: , headache (15 [45.5%]), diarrhea For (3 [9.1%]), Review and hemoptysis Only (2 [6.1%]). Only 1 13 14 182 patient (1 [3.0%]) developed shortness of breath. 15 16 17 183 On admission, among the group of 62 patients, the blood counts of patients showed 18 19 20 184 leucopenia (white blood cell count less than 4 × 10⁹/L; 19 [30.6%]) and lymphopenia 21 22 185 (lymphocyte count <1.0 × 10⁹/L; 26 [41.9%]; table 2). The D-dimer level were higher 23 24 25 186 (median D-dimer level 0.2 mg/L [IQR 0.2-0.5]). Levels of aspartate aminotransferase 26 27 187 increased in 10 patients (16.1%). Most patients had normal serum levels of procalcitonin 28 29 30 188 (procalcitonin <0.1 ng/mL; 55 [88.7%] patients). Abnormalities in chest CT images or X ray 31 32 33 189 were detected among all patients. Of the 62 patients, 52 (83.9%) had bilateral involvement 34 35 190 (table 2). The typical findings of chest CT images of infection patients on admission were 36 37 38 191 bilateral or multiple lobular or subsegmental areas of consolidation or bilateral ground-glass 39 40 192 opacity (Figure 1). Only 1 patient didn’t have pneumonia. Among the 62 patients, only 1 41 42 43 193 patient transferred to intensive care unit for acute respiratory distress syndrome and received 44 45 46 194 (Table 3). Of all the patients, 88.7% (55/62) received antiviral therapy, 47 48 195 45.2% (28/62) were administered with empirical antibiotic treatment. Besides, 25.8% (16/62) 49 50 51 196 patients were given systematic corticosteroids and gamma globulin therapy. One (1.6%) 52 53 197 patients have been discharged and no patients died up to now. Fitness for discharge was 54 55 56 198 based on abatement of fever for at least 3 days, with improvement of chest radiographic 57 58 59 199 evidence and viral clearance in respiratory samples from lower respiratory tract. 60 9

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1 2 3 4 200 5 6 7 201 Discussion 8 9 202 As of January 27, 2020, more than 2000 laboratory-confirmed 2019-nCoV infections were 10 11 12 203 reportedConfidential: in China.12 The number of infections For is increasingReview quickly. ItOnly is possible that a larger 13 14 204 number of patients with infections were not diagnosed because their symptoms were less 15 16 17 205 severe and the infection has a period of incubation. Thousands of suspected patients might be 18 19 20 206 diagnosed in the next few days. The clinical features of 2019-nCoV cases in Wuhan were not 21 22 207 same as that in other areas in China. According to our data, none of the infection cases in 23 24 25 208 Zhejiang had ever been exposed to the Huanan seafood marker, all the patients were infected 26 27 209 by human transmission. In addition, there are a large part of family clusters in Zhejiang 28 29 30 210 infected cases, which is consistent with Professor 's article and more effectively proves 31 32 10 33 211 the view of human to human transmission. This would stress on the importance of air 34 35 212 prevention. 36 37 38 213 The large part of Zhejiang patients were male patients, but the age range is larger, as 39 40 214 the 2019-nCoV also infected children and the elderly.9 There is not much difference between 41 42 43 215 the initial clinical symptoms of the Zhejiang cases and those in Wuhan. But most of the 44 45 46 216 patients in Zhejiang Province are of mild to moderate symptoms, and only a small part of 47 48 217 them have dyspnea. Only one patient developed to acute respiratory distress syndrome and 49 50 51 218 admitted to the ICU. From the laboratory test indicators, the illness of the second-generation 52 53 219 of patients are also mild. In particular, there were less patients with abnormal renal function, 54 55 56 220 lactate dehydrogenase and procalcitonin. Through media and national advocacy, the patients 57 58 59 221 with fever, cough, expectoration and other upper respiratory symptoms were asked to go to 60 10

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1 2 3 4 222 hospital at an earlier stage. Even those with the contact with other patients or suspected 5 6 7 223 patients were asked to go to hospital. We selected some patients with a course of more than 8 9 224 10 days for analysis. However, after comparing the clinical features of our patient (with 10 11 12 225 course longerConfidential: than 10 days) with Wuhan For patients, Review we found that theOnly secondary-generation 13 14 226 cases in Zhejiang Province are less severe than the primary cases in Wuhan9 (Table 4). This 15 16 17 227 phenomenon had also appeared in during the transmission of MERS-CoV. The global case 18 19 20 228 mortality of MERS-CoV was about 40%, while the mortality of second generation of 21 22 229 MERS-CoV was about 20%.13,14 23 24 25 230 There was not much differences in the antivirus therapy between Zhejiang and Wuhan. 26 27 231 However, the antibiotic treatment usage rate and corticosteroid usage rate were different. 28 29 30 232 Less than half patients received antibiotic therapy in Zhejiang Province. Whether the use of 31 32 33 233 antibiotics and steroids affects the prognosis of patients remains unknown. Till now, we have 34 35 234 no death patient in Zhejiang province and one patient has recovered after 7 days of treatment 36 37 38 235 in hospital. 39 40 236 Given that most infections in Zhejiang were secondary-generation infections, our 41 42 43 237 finding will provide valuable information to understand the clinical features of the 44 45 46 238 increasingly second-generation and later-generation patients. The clinical characteristics of 47 48 239 our study population can represent most of the patient’s infection since January 2020. Many 49 50 51 240 proposals should be administrated by the government, such as sealing off the city from all 52 53 241 outside contact of Wuhan; forbidding gathering of more than 100 persons; efficient daily 54 55 56 242 public education of 2019-nCoV precaution; encouraging people to cancel the traditional 57 58 59 243 family gathering during Chinese Lunar New Year and extending the New Year holiday to 60 11

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1 2 3 4 244 prevent large-scale spreading. 5 6 7 245 Our study has several limitations. Firstly, there are only 62 cases were included in our 8 9 246 study. During the period of data collection, a large number of patients showed up So we just 10 11 12 247 collectedConfidential: most but not all of the patients withFor laboratory Review confirmed illness Only in Zhejiang 13 14 248 Province in that time. Secondly, the patients were only from Zhejiang province which may 15 16 17 249 not be able to fully reveal the clinical features of secondary infection patients. Thirdly, at the 18 19 20 250 time of submission of the manuscript, most patients were still not discharged, so we were 21 22 251 unable to estimate either the case fatality rate or predictors of fatality. Moreover, the course 23 24 25 252 of some of our patients may be shorter than 10 days of observation period, which may cause 26 27 253 the bias of clinical observation characteristics. 28 29 30 254 In conclusion, 2019-nCoV was easily transmitted from human to human At present, the 31 32 33 255 symptoms of secondary-generation patients are relatively mild. At present, there is no 34 35 256 effective drug treatment and vaccine. It is still necessary to strengthen virus monitoring in 36 37 38 257 time and to develop drugs and vaccines for 2019-nCoV as soon as possible. 39 40 258 41 42 43 259 Acknowledgments. We thank Dr. Song-Jia Tang for the help of English polishing. 44 45 46 260 47 48 261 Footnotes 49 50 51 262 Contributors: XW Xu and LJ Li conceptualized the paper. XX Wu analyzed the data with 52 53 263 input from JF Sheng, KJ Xu, XG Jiang, LJ Ying, CL Ma, SB Li, HY Wang, S Zhang, HN 54 55 264 Gao, HL Cai and YQ Qiu. XW Xu and XX Wu wrote the initial draft with all authors 56 57 58 265 providing critical feedback and edits to subsequent revisions. All authors approved the final 59 60 266 draft of the manuscript. The corresponding author attests that all listed authors meet 12

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1 2 3 4 267 authorship criteria and that no others meeting the criteria have been omitted. 5 6 268 7 8 9 269 Funding: No funding. 10 11 12 270 Confidential: For Review Only 13 14 271 Competing interests. The authors declared no conflicts 15 16 17 272 18 19 273 Ethical approval: This study was approved by the Ethics Committee of the First Affiliated 20 21 22 274 Hospital, Zhejiang University School of Medicine (2020IIT A0001). 23 24 25 275 26 27 276 28 29 30 277 31 32 278 33 34 35 279 36 37 38 280 39 40 281 41 42 43 282 44 45 283 46 47 48 284 49 50 51 285 52 53 286 54 55 56 287 57 58 288 59 60 13

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1 2 3 4 289 References: 5 6 7 290 01. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in 8 9 291 China, 2019. N Engl J Med 2020; published online Jan 24. doi: 10.1056/NEJMoa2001017. 10 11 12 292 02. H,Confidential: Stratton CW, Tang YW. Outbreak For of PneumoniaReview of Unknown Only Etiology in Wuhan 13 14 293 China: the Mystery and the Miracle. J Med Virol 2020; published online Jan 16. doi: 15 16 17 294 10.1002/jmv.25678. 18 19 20 295 03. Ji W, Wang W, Zhao X, Zai J, Li X. Homologous recombination within the spike 21 22 296 glycoprotein of the newly identified coronavirus may boost cross-species transmission from 23 24 25 297 snake to human. J Med Virol 2020; published online Jan 22. doi: 10.1002/jmv.25682. 26 27 298 04. Zhou P, Yang X-L, Wang X-G, et al. Discovery of a novel coronavirus associated with 28 29 30 299 the recent pneumonia outbreak in 2 humans and its potential bat origin. bioRxiv preprint first 31 32 33 300 posted online Jan 23, 2020; doi: http://dx.doi.org/10.1101/2020.01.22.914952 34 35 301 05. de Groot RJ, Baker SC, Baric RS, et al. Middle East respiratory syndrome coronavirus 36 37 38 302 (MERS-CoV): announcement of the Coronavirus Study Group. Journal of virology 39 40 303 2013;87:7790-2. 41 42 43 304 06. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a 44 45 46 305 novel coronavirus from a man with pneumonia in Saudi Arabia. The New England journal of 47 48 306 medicine 2012;367:1814-20. 49 50 51 307 07. WHO. Middle East respiratory syndrome coronavirus (MERS-CoV). November, 2019. 52 53 308 http://www.who.int/emergencies/mers-cov/en/ (accessed Jan 19, 2020). 54 55 56 309 08. Xu XT, P, Wang JF et al. Evolution of the novel coronavirus from the ongoing 57 58 59 310 Wuhan outbreak and modeling of its spike protein for risk of human transmission. SCIENCE 60 14

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1 2 3 4 311 CHINA Life Sciences; doi: 10.1007/s11427-020-1637-5. 5 6 7 312 09. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel 8 9 313 coronavirus in Wuhan, China. The Lancet 2020; Published Online January 24. 10 11 12 314 https://doi.org/10.1016/Confidential: S0140-6736(20)30183-5. For Review Only 13 14 315 10. Chan JF-W, Yuan S, Kok K-H, et al. A familial cluster of pneumonia associated with the 15 16 17 316 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. 18 19 20 317 The Lancet 2020; Published Online January 24. https://doi.org/10.1016/ 21 22 318 S0140-6736(20)30154-9. 23 24 25 319 11.https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200125-sitrep-5 26 27 320 -2019-ncov.pdf?sfvrsn=429b143d_4. 28 29 30 321 12.http://www.chinacdc.cn/jkzt/crb/zl/szkb_11803/jszl_11811/202001/P02020012754464842 31 32 33 322 0736.pdf (In Chinese). 34 35 323 13. Kim KH, Tandi TE, Choi JW, et al. Middle East respiratory syndrome coronavirus 36 37 38 324 (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health 39 40 325 implications. J Hosp Infect 2017;95:207-213. 41 42 43 326 14. WHO. Middle East respiratory syndrome coronavirus (MERS-CoV). 44 45 46 327 https://www.who.int/emergencies/mers-cov/en/.(accessed Jan 27, 2020) 47 48 328 49 50 51 329 52 53 330 54 55 56 331 57 58 59 332 60 15

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1 2 3 4 333 Table 1. Demographic and Epidemiologic Characteristics of 62 Patients Infected with 2019-nCoV in 5 6 7 334 Zhejiang, China. 8 9 Patients with course 10 11 12 CharacteristicsConfidential:All For patients (n=Review 62) longer thanOnly 10 days 13 14 (n= 33) 15 16 17 Age yr 41 (32-52) 45 (37-54.5) 18 19 20 18 and younger 2 (3.2) 0 (0) 21 22 19-40 25 (40.3) 10 (30.3) 23 24 25 41-65 33 (53.2) 22 (66.7) 26 27 66 and above 2 (3.2) 1 (3.0) 28 29 30 Sex 31 32 33 Men 36 (58.1) 19 (57.6) 34 35 Women 27 (43.5) 14 (42.4) 36 37 38 Coexisting condition 39 40 Any 20 (32.3) 13 (39.4) 41 42 43 Hypertension 5 (8.1) 4 (12.1) 44 45 46 Diabetes 1 (1.6) 1 (3.0) 47 48 Chronic obstructive pulmonary 49 50 1 (1.6) 1 (3.0) 51 disease 52 53 Cerebrovascular disease 1 (1.6) 1 (3.0) 54 55 56 Renal diseases 1 (1.6) 0 (0) 57 58 59 Liver disease 7 (11.3) 4 (12.1) 60 16

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1 2 3 4 Familial cluster 21 (33.9) 9 (27.3) 5 6 7 signs and symptoms 8 9 Fever 48 (77.4) 26 (78.8) 10 11 12 HighestConfidential: temperature (℃) For Review Only 13 14 < 37.3 14 (22.6) 9 (27.3) 15 16 17 37.3-38.0 22 (35.5） 10 (30.3) 18 19 20 38.01-39.0 18 (29.0) 9 (27.3) 21 22 > 39.0 8 (12.9) 5 (15.2) 23 24 25 Cough 50 (80.6) 27 (81.8) 26 27 Myalgia or fatigue 32 (51.6) 19 (57.6) 28 29 30 Expectoration 35 (56.5) 19 (57.6) 31 32 33 Hemoptysis 32 (3.2) 2 (6.1) 34 35 Headache 21 (33.9) 15 (45.5) 36 37 38 Diarrhoea 3 (8.1) 3 (9.1) 39 40 Incubation period 4 (3-5) 3.0 (3.0-4.0) 41 42 43 Respiratory rate >24 breaths per min 2 (3.2) 1(3.0) 44 45 46 Duration from illness onset to first 47 2 (1-4.3) 6.5 (5.0-9.0) 48 admission 49 50 51 335 Data are median (IQR) or n/N (%), where N is the total number of patients with available data. 52 53 336 54 55 56 337 57 58 59 338 60 17

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1 2 3 4 339 Table 2: Laboratory findings and chest radiographs of patients infected with 2019-nCoV on admission to 5 6 7 340 hospital 8 9 341 10 11 12 Confidential: For ReviewPatients Only with course longer 13 All patients (n= 62) 14 than 10 days (n= 33) 15 16 17 White blood cell count, x109/L 4.7 (3.5-5.8) 4.5 (3.1-6.1) 18 19 20 <4 19 (30.6) 13 (39.4) 21 22 4-10 42 (67.7) 20 (60.6) 23 24 25 >10 1 (1.6) 0 (0) 26 27 Neutrophil count 2.9 (2.0-3.7) 2.8 (1.7-3.9) 28 29 30 Lymphocyte count 1.0 (0.8-1.5) 1.0 (0.7-1.4) 31 32 33 <1.0 26 (41.9) 15 (45.5) 34 35 ≧1.0 36 (58.1) 18 (54.5) 36 37 38 Haemoglobin, g/L 137.0 (128.8-152.3) 137.5 (129.0-149.5) 39 40 Platelet count, 176.0 (135.8-215.5) 172.5 (128.8-202.8) 41 42 43 <100 3 (4.8) 3 (9.1) 44 45 46 ≧100 59 (95.2) 30 (90.9) 47 48 D-dimer, mg/L 0.2 (0.2-0.5) 0.2 (0.2-0.6) 49 50 51 Alanine aminotansferase, U/L 22 (14-34) 22.5 (13.6-35.1) 52 53 Aspartate aminotansferase, U/L 26 (20-32) 27.5 (18.5-34.7) 54 55 56 <40 52 (83.9) 28 (84.8) 57 58 59 ≧40 10 (16.1) 5 (15.2) 60 18

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1 2 3 4 Potassium, mmol/L 3.7 (3.5-3.9) 3.6 (3.5-3.9) 5 6 7 Sodium, mmol/L 139 (127-141) 138.6 (136.9-140.6) 8 9 Creatine, umol/L 72.0 (61.0-84.0) 71.5 (61.0-82.2) 10 11 12 ≦133 Confidential:59 For(95.2) Review33 Only(100) 13 14 >133 3 (4.8) 0 (0) 15 16 17 Creatine kinase, U/L 69.0 (40.5-101.0) 60.0 (40.0-106.8) 18 19 20 ≦185 57 (91.9) 31 (93.9) 21 22 >185 5 (8.1) 2 (6.1) 23 24 25 Lactate dehydrogenase, U/L 205.0 (184.0-260.5) 233.5 (198.0-312.3) 26 27 ≦245 45 (72.6) 19 (57.6) 28 29 30 >245 17 (27.4) 14 (42.4) 31 32 33 Procalcitonin, ng/mL 0.04 (0.03-0.06) 0.4 (0.035-0.06) 34 35 <0.1 55 (88.7) 31 (93.9) 36 37 38 ≧0.1 7 (11.3) 2 (6.1) 39 40 Bilateral involvement of chest 41 42 52 (83.9) 32 (97.0) 43 radiographs 44 45 46 Pneumonia 61 (98.4) 33 (100) 47 48 342 Data are median (IQR) or n/N (%), where N is the total number of patients with available data. 49 50 51 343 52 53 344 54 55 56 345 57 58 59 346 60 19

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1 2 3 4 347 Table 3. Treatments and outcomes of patients infected with 2019-nCoV 5 6 7 All patients (n= Patients with course 8 9 62) longer than 10 days (n= 33) 10 11 12 AdmissionConfidential: to Intensive Care Unit 1 (1.6)For Review1 (3.0) Only 13 14 Acute respiratory distress syndrome 1 (1.6) 1 (3.0) 15 16 17 Treatment 18 19 20 Antiviral therapy 55 (88.7) 31 (93.9) 21 22 Antibiotic therapy 28 (45.2) 16 (48.5) 23 24 25 Corticosteroid and gamma globulin 26 16 (25.8) 11 (33.3) 27 therapy 28 29 30 Prognosis 31 32 33 Hospitalization 61 (98.4) 32 (97.0) 34 35 Discharge 1 (1.6) 1 (3.0) 36 37 38 Death 0 0 39 40 41 348 42 43 349 Data are median (IQR) or n/N (%), where N is the total number of patients with available data. 44 45 46 350 47 48 351 49 50 51 352 52 53 54 353 55 56 354 57 58 59 355 60 20

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1 2 3 4 356 Table 4 The compare of the clinical features between our with NO ICU care patients reported by Bin Cao 5 6 7 NO ICU care Patients with course 8 All patients 9 10 Characteristics patients longer than 10 days 11 (n= 62) 12 Confidential: For Review Only (n=28) (n= 33) 13 14 15 Fever 27(96%) 48 (77.4) 26 (78.8) 16 17 18 Highest temperature 19 20 < 37.3 1(4.0) 14 (22.6) 9 (27.3) 21 22 23 37.3-38.0 5(18.0) 22 (35.5） 10 (30.3) 24 25 38.01-39.0 11(39.0) 18 (29.0) 9 (27.3) 26 27 28 > 39.0 11(39.0) 8 (12.9) 5 (15.2) 29 30 31 Respiratory rate >24 32 33 breaths per min 4(14.0) 2 (3.2) 1(3.0) 34 35 36 Bilateral involvement of 37 38 chest radiographs 27(96%) 52 (83.9) 32 (97.0) 39 40 41 357 42 43 44 358 45 46 359 47 48 49 360 50 51 52 361 53 54 362 55 56 57 363 58 59 364 60 21

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1 2 3 4 365 Figure 1: Transverse chest CT images of the patient. Transverse chest CT images from a 5 6 7 366 32-year-old man showing ground-glass opacity and consolidation of lower lobe of right lung 8 9 367 near the pleura on day 1 after symptom onset (A), and bilateral ground-glass opacity and 10 11 12 368 consolidationConfidential: on day 7 after symptom onset For (B). Review Only 13 14 369 15 16 17 370 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 22

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1 2 3 4 5 6 7 8 9 10 11 Confidential: For Review Only 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 Transverse chest CT images of the patient. Transverse chest CT images from a 32-year-old man showing 46 ground-glass opacity and consolidation of lower lobe of right lung near the pleura on day 1 after symptom 47 onset (A), and bilateral ground-glass opacity and consolidation on day 7 after symptom onset (B). 48 159x250mm (96 x 96 DPI) 49 50 51 52 53 54 55 56 57 58 59 60 https://mc.manuscriptcentral.com/bmj