Clinical Characteristics of SARS-CoV-2 Infections Involving 325 Hospitalized Patients outside Wuhan

Background/Objective To date, the clinical features of SARS-CoV-2 infections were reported mainly based on cases in Wuhan. We aimed to report the clinical features of SARS-CoV-2 infections outside Wuhan. Methods We analyzed 325 SARS-COV-2 infection patients hospitalized in Shanghai Public Health Clinical Center. The epidemiological, demographic, and clinical data were compared between severe and non-severe cases. Results Of 325 patients, the median age was 51 years, 167 (51.4%) were men, and 107 (32.9%) had underlying diseases. 159 (48.9%) visited Wuhan or had contacted with people from Wuhan, but 57 (17.5%) had no clear epidemiological history. Compared with non-severe patients (n=299, 92%), severe patients (n=26, 8%) were older, had more common underlying disorder, more common lymphopenia, and higher D-dimer, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, creatinine, procalcitonin, C-reactive-protein, and troponin I level. The common complications included secondary infection (12.3%), acute cardiac injury (9.2%), ARDS (5.5%), acute kidney injury (5.8%), and shock (4.9%). To Mar 12, 311 (95.7%) patients were discharged, 3 (0.9%) died, and 11 (3.4%) still hospitalized. Conclusions The severity rate and fatality rate were low if the measures (early isolation, early diagnosis and early management) were undertaken at the early time of the outbreak. LDH, lactate dehydrogenase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; The P values indicate differences between severe and non-severe patients. P < 0.05 was considered statistically signicant.


Background
Since November 2019, the rapid outbreak of 2019 novel coronavirus disease (COVID-19), which caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global public health emergency. Human-to-human transmission has been con rmed for SARS-CoV-2 [1] . To date, the novel coronavirus has spread to different countries worldwide, and the number of con rmed cases and death cases has been quickly growing [2] . As of March 12th, 2020, there have been 118,326 con rmed cases and 4,292 deaths globally, among them, 80,955 con rmed cases and 3,162 deaths in China [2] .
The clinical features of SARS-CoV-2 infection have been studied in Wuhan, China. First, Huang et al reported the clinical characteristics and outcomes of 41 initial patients with SARS-CoV-2 infection who were linked to the Wuhan Hua-nan Seafood Market [3] . Subsequently, Chen et al reported the epidemiological and clinical characteristics of 99 cases of SARS-CoV-2 pneumonia in Wuhan Jinyintan Hospital [4] . After that, Wang et al reported the clinical characteristics of 138 hospitalized patients with SARS-CoV-2-infected pneumonia at Zhongnan Hospital of Wuhan University in Wuhan, China [5] . Recently, Guan et al reported the clinical characteristics of 1099 patients with con rmed SARS-CoV-2 infection, 71.8% came in contact with people from Wuhan, and 43.95% were local residents of Wuhan [6] . In a word, all these studies were based on cases in Wuhan, China. There is a lack of data outside Wuhan.
Although Chang et al reported the clinical features of 13 SARS-CoV-2 infection patients outside Wuhan [7] , it is limited by small sample sizes and lack of data in severe patients. To date, little is known about the clinical characteristics of SARS-CoV-2 infection outside Wuhan. Therefore, in this study, we report the clinical features of 325 con rmed SARS-CoV-2 infection patients hospitalized in Shanghai, China.

Patients
A total of 325 consecutive patients with con rmed SARS-CoV-2 infection hospitalized in Shanghai Public Health Clinical Center, a designated tertiary teaching hospital for the diagnosis and treatment of con rmed SARS-CoV-2 infection in Shanghai, China, from January 20th, 2020 to February 29th, 2020, were enrolled. The 325 SARS-CoV-2 infection patients were grouped into severe cases (n = 26) and nonsevere cases (n = 299). The clinical outcomes were monitored up to March 12, 2020, the nal date of follow-up.

Diagnostic criteria
Patients with possible SARS-CoV-2 infection were quarantined, and throat swab samples were sent to the Chinese Center for Disease Control and Prevention for detection of SARS-CoV-2. A con rmed case was de ned as a positive result with SARS-COV-2 nucleotides using real-time polymerase-chain-reaction assay according to the WHO guidance [8] . Severe patients were identi ed as any one of the followings: (1) Respiratory rates ≥ 30/min; (2) Oxygen saturation ≤ 93% in a resting state; (3) Oxygenation index (PaO2/FiO2) ≤ 300 mmHg; (4) Require mechanical ventilation; (5) Shock; (6) Combined with other organ failures and needed treatment in ICU.
Acute respiratory distress syndrome (ARDS) was de ned according to the Berlin de nition [9] . Acute cardiac injury was de ned as the serum troponin I was above the 99th percentile upper limit of normal [3] .
Acute kidney injury (AKI) was de ned according to the KDIGO clinical practice guidelines [10] . Secondary infection was de ned as the patients had clinical symptoms or signs of nosocomial infection, and a positive culture of a new pathogen from a lower respiratory tract specimen or blood samples taken ≥ 48 h after admission [11] .

Data collection
We reviewed the medical records including clinical charts, nursing records, laboratory ndings, and radiological tests for the 325 SARS-CoV-2 infection patients. The data about demographics, epidemiological histories, clinical characteristics, laboratory ndings, radiological manifestations, complications, and clinical outcomes were obtained with data collection forms.

Statistical analysis
The normality test was performed for continuous variables using the Kolmogorov-Smirnov test. Nonnormal distribution continuous variables were expressed as medians and interquartile ranges (IQR), and compared with the Mann-Whitney U test. Categorical variables were showed as the counts and percentage, and compared by chi-square test. All signi cance tests were two-tailed, and p < 0.05 was considered statistically signi cant. All statistical analyses were done using SPSS software version 15.0 (SPSS Inc. USA).

Demographics and Epidemiological Characteristics of Enrolled Patients
The demographics and epidemiological characteristics of enrolled patients were presented in Table 1. The median age was 51 years (IQR, 36-64 years), and 167 (51.4%) were men. 216 (66.5%) of patients were aged 15-59 years, 75 (23.1%) were aged 60-69 years, and 34 (10.5%) were aged ≥ 70 years. 26 and 299 patients were categorized into severe and non-severe subgroups, respectively. The median age was signi cantly higher in severe cases as compared with non-severe cases (65 vs 49 years, p < 0.001). The proportion of male patients in severe cases was signi cantly higher than that in non-severe cases (76.9% vs 49.2%, p = 0.007).

Clinical Features and Outcomes of SARS-CoV-2 Infection Patients
The clinical features and outcomes of patients were showed in  The P values indicate differences between severe and non-severe patients. P < 0.05 was considered statistically signi cant.

Laboratory Findings of SARS-CoV-2 Infection Patients
The laboratory ndings of patients were presented in Table 3.    In this study, most of the patients were aged 15-59 years, and only 34 patients were older than 70 years.

Discussion
This might be related to limited travel of older patients rather than decreased susceptibility. Fever (80.9%), cough (51.4%), and fatigue (19.1%) are the common clinical manifestations in this study, consistent with previous studies including Wuhan patients, which also showed fever (83-98.6%), cough (59.4-82%), and fatigue (69.6%) are the most common clinical manifestations [3][4][5] . There was no statistic difference was found in the symptoms between severe and non-severe cases, besides dyspnea (30.8% vs 6.7%, p < 0.001). Previous studies also found that patients treated in the ICU were more likely to have dyspnea (63.9% vs 19.6%, p < 0.05) compared with non-severe patients [3][4][5] .. The results suggested that dyspnea might be an early signal for disease severity progression.
13 (4.3%) patients in non-severe sub-group had no radiologic abnormality, and all patients in severe subgroup had radiologic abnormality. 18 (6.0%) patients in non-severe sub-group were asymptomatic, and all patients in severe sub-group had fever, cough, or fatigue. The 18 asymptomatic patients were potential transmission sources, and transfered SARS-CoV-2 to their close contacts. The ndings remained consistent with the latest reports, including pneumonia was not mandatory for SARS-CoV-2 infection [6] , and human-to-human transmission happened from asymptomatic individuals [14] . Our results advocate the focus that identifying and managing asymptomatic patients is important to stop the spread of SARS-CoV-2 outbreak.
In this study, for the 325 SARS-CoV-2 infection patients in Shanghai, China, the severity rate is 8%, and the fatality rate is 0.9%, which was lower than that reported from Wuhan. Huang et al included 41 SARS-CoV-2 infection patients in Wuhan Jinyintan Hospital, and reported 13 (32%) patients were admitted to an ICU and 6 (15%) died [3] . Chen et al included 99 SARS-CoV-2 pneumonia patients in Wuhan Jinyintan Hospital, and reported 17 (17%) patients developed ARDS, and 11 (11%) patients died [4] . Wang et al included 138 SARS-CoV-2-infected pneumonia patients at Zhongnan Hospital of Wuhan University in Wuhan, China, and reported 36 (26.1%) patients were transferred to the ICU and 6 (4.3%) died [5] . Our results outside Wuhan suggested that the severity rate and fatality rate of SARS-CoV-2 infection were low if the measures (early isolation, early diagnosis, and early management) were undertaken at the early time of the outbreak. The lack of health workers and delayed central diagnosis, treatment and isolation might have led to the increased severity rate and fatality rate in Wuhan, China.
The current SARS-CoV-2 outbreak is the third epidemic caused by coronavirus in the 21st century, following severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The fatality rate of SARS is more than 40% in patients over 60 years [12] , and the fatality rate of MERS is 30% [13] . The reported mortality rate of SARS-CoV-2 infection uctuated from a low of 4.3% to a high of 15% in Wuhan, China [3][4][5] , which is lower than that reported from SARS and MERS. The outbreak of SARS-CoV-2 infection may be attributable to relatively late identi cation of the etiologic agent, the highly contagious of SARS-CoV-2, and the relatively weak ability of the host to clear the virus while asymptomatic Our study has some limitations. Firstly, 11 (3.4%) patients were still hospitalized. Those patients need to be followed up, and further outcomes need to be noted. Secondly, this study is a single-center study.
Thirdly, there were no children patients in this study, because the SARS-CoV-2 infection children hospitalized at the Children's Hospital of Fudan University, a designated hospital for children in Shanghai.

Conclusion
In conclusion, SARS-CoV-2 caused a spread of outbreak with human-to-human transmission in Shanghai, a city outside Wuhan, with a median incubation period of 7 days. The common symptoms include fever, dry cough, and fatigue. The measures (early isolation, early diagnosis, and early management) were undertaken at the early time of the outbreak, contributed to the decreased transmission and a relatively low severe rate and fatality rate in Shanghai, China.