Clinical Characteristics of 107 Patients with COVID-19 in Ningbo, China: Single Center Experience Outside Hubei

Background Since December 2019, there has be an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China. Nowadays, it rapidly spread across the country and then the worldwide. We aimed to investigate the clinical characteristics of patients with COVID-19. Methods The patients with conrmed COVID-19 admitted between January 25 and February 10, 2020, were enrolled. Epidemiological, demographic, clinical, laboratory, radiological data, and antivirus therapies, were retrospectively collected and analyzed. The 90-day follow-up of these patients was also performed. Results A total of 107 patients were included. The median age was 55.0 years (range from 18.0 to 85.0 years), and 72 (67.3%) were female. Ninety-three (86.9%) of the patients had a history of contacting with residents from Wuhan (n=31), or contacting with conrmed COVID-19 patients (n=62) within 2 weeks. Fifty-eight (54.2%) had a family cluster onset. Fever and cough were the most common symptoms. Only two patients had diarrhea. The most common underlying disease was hypertension. Lymphopenia was observed in 26 patients. Fifty-two patients with an elevated level of IL-6. On admission, bilateral patchy shadowing and ground-glass opacity were the typical radiological ndings on chest computed tomography. Six patients had an intensive care unit (ICU) stay. Antivirus therapy was performed to all patients. 105 patients discharged with an improved condition, and no death was occurred during our 90-day follow-up for these patients. Conclusions Patients with COVID-19 in our hospital had relatively mild symptoms, and good prognosis. This study also highlights the importance of human-to-human transmission in COVID-19.


Introduction
Since December 2019, a novel coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged in Wuhan city, Hubei province, China, and rapidly spread across the country and then the worldwide. Due to its fast transmission, outbreak of SARS-Co-2 has raised a global public health concern and attracted a wide attention.
SARS-CoV-2 could cause different clinical conditions, which named coronavirus disease 2019 (COVID-19) by the WHO. Among COVID-19, pneumonia is a common clinical manifestation, and can progress to severe acute respiratory syndrome, and even death. SARS-CoV-2 related pneumonia has been characterized, as well as the difference between the severe and non-severe cases [1][2][3][4]. Very recently, limited studies demonstrated the clinical characteristics of patients with COVID-19 [2,3,[5][6][7][8]. Increasing evidence indicated the presence of person-to-person transmission of SARS-CoV-2. To date, although speci c therapeutic drugs or vaccines for COVID-19 are not available, multi-center clinical trials to explore the e cacy and safety of antivirus agents are in progress. However, with its globally continuously evolving and expansion, it is urgent to unravel more about SARS-CoV-2 and COVID-19. Moreover, to the best of our knowledge, nowadays, rare studies presented the follow-up of patients with COVID-19. The aims of this study are to describe the epidemiological and clinical features of 107 inpatients with laboratory-con rmed COVID-19 outside Wuhan, and the 90-day follow-up of these patients.

Patients
All hospitalized patients with laboratory-con rmed COVID-19, admitted to Hwa Mei Hospital from January 25 to February 10, were enrolled. Hwa Mei Hospital, located in Ningbo, Zhejiang province, is a tertiary teaching hospital and is designated for patients with COVID-19. This study was approved by the institutional ethics board of Hwa Mei Hospital, University of Chinese Academy of Sciences (PJ-NBEY -KY-2020-047-01). Oral consent was obtained from patients due to emerging infectious diseases.

Data Collection
The medical records of patients with COVID-19 were retrospectively reviewed by the attending physicians of our team. Clinical data, such as clinical manifestations, laboratory tests, imaging examinations, antivirus therapies, and epidemiological history, were extracted from the electronic records. The incubation period was de ned as described previously [5]. The day of disease onset was de ned as the time when the rst symptom occurred. The time gap between disease onset and admission was noted.
Patient with COVID-19 was con rmed when a positive result was recorded by real-time reversetranscriptase polymerase-chain-reaction (RT-PCR) test for throat swab, or sputum specimens [2], and only these con rmed hospitalized patients were included for further analysis. The patients with COVID-19 were classi ed as non-severe (including uncomplicated illness and mild pneumonia) and severe according to the World Health Organization interim guidance [9]. Patients discharged when following criteria were met: a) body temperature normal for over 3 days, b) respiratory symptoms markedly improved, c) chest imaging suggesting in ammation alleviated remarkably, and d) ≥ 2 consecutively negative tests for respiratory sample for SARS-CoV-2 RNA with an interval over 24 h. The 90-day follow-up was carried out by the physicians communicating with the patients.

Statistical analysis
Categorical variables were recorded as frequencies rates and percentages, and continuous variables were noted by median, and interquartile range (IQR) values. SPSS (version 19.0) was used for analyzing the data.

Clinical characteristics
A total of 107 patients with con rmed COVID-19 were enrolled. The demographic and clinical data are summarized in Table 1. Of the 107 patients, the median age was 55.0 years (range from 18.0 to 85.0 years, IQR, 39.0 to 64.0), and 72 (67.3%) were female. Ninety-three (86.9%) patients had a history of contacting with residents from Wuhan (n = 31), or contacting with patients with con rmed COVID-19 (n = 62) within 2 weeks. Fifty-eight (54.2%) of the 107 patients had a family cluster onset. Of the 107 patients, the median incubation period was 6 days (range from 1.0 to 17.0 days, IQR, 2.0 to 7.0), and the median duration between disease onset and admission were 6 days (range from 1 to 14 days, IQR, 4 to 9). No healthcare workers were infected by SARS-CoV-2 in this study, and all the cases were domestic.   There were four patients without symptoms had a positive throat swab for SARS-CoV-2 by RT-PCR. Among the 103 remaining patients, on admission the most common symptoms were fever (n = 79, 73.8%), cough (n = 44,41.1%), following by expectoration (n = 13, 12.2%) and fatigue (n = 7, 6.5%) ( Table 1). Of the 79 patients with fever, most patients (n = 73, 92.4%) had a body temperature less than 39℃. Only one (0.9%), two (1.9%), and three (2.8%) patients presented with poor appetite, diarrhea, and nausea, respectively.

Clinical Outcomes
The median length of hospitalization weas 14.0 days (IQR, 10.0 to 18.0, range from 2.0 to 31.0 days). Thirteen (12.1%) patients progressed to severe pneumonia, and 6 of them had an ICU stay due to the presence of organ dysfunction. However, 105 of the 107 patients discharged with an improved condition. The remaining two patients who transferred to another hospital still stayed in ICU (one underwent liver transplant before infected by SARS-CoV-2, and another underwent lung transplant due to severe COVID-19). As of May 19, 2020, 90-day follow-up for the discharged 105 patients with con rmed COVID-19 was completed, and no death was occurred during our follow-up.

Discussion
This study rstly reported the 90-day follow-up of patients with COVID-19, and all the cases survived during our follow-up. The median duration between disease onset and admission were 6 days in this study, which was shorter than those cases reported from Wuhan [2,3]. In addition, all of the patients received an antivirus treatment in this study. Actually, to explore the e cacy of antivirus agents for SARS-  [7,8]. On the other hand, studies from Wuhan reported relative high rates of patients who had an ICU stay [1,3]. No death happened in our study, while the mortality rate of COVID-19 ranged from 0 to 15% in previous studies [1,2,[4][5][6][7][8]. These discrepancies may result from the various sample sizes, inclusion criteria, and different stages of the disease. Taken together, early detection and early intervention likely contributes to improve the prognosis of COVID-19.
Currently, the con rmed origin of SARS-CoV-2 is yet unknown. However, increasing evidence demonstrates it could spread effectively among human beings [8,10,11]. Most (86.9%) patients had a history of contacting with residents of Wuhan or the patients with COVID-19 in the present study, which is in agreement with previous studies [4,5,8]. Surprisingly, over 50% of the patients had a family cluster onset in this study. These results indicated that the importance of human-to-human transmission in SARS-CoV-2. The main transmission routes of SARS-CoV-2 are considered to be respiratory droplets and direct contact [5]. Gastrointestinal tract and urine are potential transmission routes of SARS-CoV-2, which needs to be con rmed. To date, with the threat of COVID-19 worldwide, effective measures to block the transmission routes are urgent.
A few patients were without any symptoms after being infected by SARS-CoV-2. However, fever (mainly mild to moderate) and cough were the most common symptoms of our patients with COVID-19 in this study, which was in agreement with recent studies [2,3,5,6]. Gastrointestinal symptoms were not common in COVID-19. The most common underlying disease was hypertension in this study. These were in accordance with previous studies [1,2,5,6,12].
Approximately a quarter of the patients had a lymphopenia in this study, which was lower than those reported in recent studies [2,[5][6][7][8]. Different disease stages might result in this. Increased levels of in ammatory factors CRP and ESR were frequently occurred in the present study, while upregulated levels of PCT were uncommonly observed in patients with COVID-19. The level of LDH was increased in a relative high rate of patients in this study. These results were similar with recent publications [2,5,7].
As showing in this study, chest CT scan of patients with COVID-19 could be normal, lung consolidation, ground-glass opacity, and bilateral patchy shadowing, and the latter two were most common. These ndings were consistent with published studies [1,5,[13][14][15]. Different stages of COVID-19 may result in various radiological manifestations [16].
This study has limitations. First, respiratory samples were used to con rm the presence of COVID-19 by RT-PCR. Due to newly emerging of SARS-CoV-2, the false negative may be inevitably existed, which would in uence the ndings of the study. Second, no pediatric patients included in the present study, because Hwa Mei Hospital is an adult hospital, and pediatric patients with COVID-19 were designated to a children hospital. Third, cases were all from one hospital in this study.

Conclusions
In the present study, among the 107 domestic hospitalized patients with con rmed COVID-19 in Ningbo, China, most (89%) had a history of contacting with residents in Wuhan or patients with COVID-19. Further, more than half of patients had a family cluster. A 90-day follow-up of the discharged patients with COVID-19 revealed a satisfactory prognosis, which may be attributed to early detection and early intervention.

Consent for publication
Not applicable.
Availability of data and materials