The rapid spread of coronavirus disease 2019 (COVID-19) has become a focus of public health concern since November 2019. According to the World Health Organization report with data updated on 6 November 2020, the COVID-19 pandemic has caused over 48.5 million confirmed cases and over 1.23 million deaths worldwide.1 The 2019 novel coronavirus has been designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses. The Law on Prevention and Control of Infectious Diseases, China categorises COVID-19 as a Category B infectious disease, but it is supervised as Category A in China.

During the early stage of the COVID-19 outbreak, especially before the lockdowns of Wuhan City and then Hubei Province, some people who had been infected by the virus travelled back to Hangzhou from Wuhan. Then the disease was disseminated by person-to-person transmission within the Hangzhou community. A familial cluster of the disease occurred during the self-isolation and home quarantine period because of intrafamilial transmission. The XiXi Hospital of Hangzhou was immediately designated by the government as the only municipal hospital for diagnosis and therapy of patients with COVID-19 in Hangzhou City. We reviewed and analysed the hospital’s medical records to determine the epidemiological and clinical characteristics of these cases.

This retrospective observational study was performed on the records of patients who were treated from 15 January 2020 to 30 March 2020 at the XiXi Hospital of Hangzhou. The study adhered to the ethical principles of medical research involving human subjects of the World Medical Association Declaration of Helsinki and was approved by the Ethics Committee of the XiXi Hospital of Hangzhou. Informed consent was waived because of the retrospective nature of this study.

The following instruments and materials were used in the study: a blood gas analyser (Radiometer ABL90, Denmark), an automatic haematology analyser (SYSMEX XE-5000, Japan), an automatic coagulation analyser (SYSMEX CS5100, Japan), an automatic biochemistry analyser (Beckman Coulter AU5831, US), and a vacuum blood collection tube (BD Vacutainer containing lithium heparin anticoagulant, US). Body surface temperature was detected by a non-contact infrared thermometer (JXB-178, Berrcom, Guangzhou). A fever was defined as a body temperature >37.0°C. Chest computed tomography (CT) scans (GE Revolution EVO, US) were conducted on every patient. Standard nucleic acid detection for SARS-CoV-2 was conducted at the Hangzhou Municipal Center for Disease Control and Prevention by the way of qualitative polymerase chain reaction (PCR). The diagnostic criteria were based on the recommendation of the National Institute for Viral Disease Control and Prevention, China (http://ivdc.chinacdc.cn/kyjz/202001/ t20200121_211337.html).

Epidemiological and demographic information about patients with COVID-19 was collected and reviewed, including age, gender, height, weight, co-morbidities like hypertension and type 2 diabetes mellitus, history of smoking, drinking and surgery, and recent travel and residence history. The clinical features and symptoms were recorded and reviewed during hospital visits. The results of the first laboratory tests performed on hospital admission were analysed. During hospitalisation, clinical and laboratory characteristics including SARS-CoV-2 nucleic acid test results were evaluated. Radiological manifestations on chest CT scan were examined. The outcomes of treatment were checked, and the patients received follow-up.

Two attending doctors were responsible for the diagnosis and treatment of all patients with COVID-19 according to the clinical diagnosis guideline and treatment protocol for COVID-19 released by the National Health Commission & National Administration of Traditional Chinese Medicine, China and the Zhongnan Hospital of Wuhan University Novel Coronavirus Management and Research Team.2 3 The radiological diagnosis of chest CT scans was decided by two attending radiologists and another two attending clinical doctors independently.

The laboratory-confirmed cases were classified according to severity as mild (ie, mild symptoms without pneumonia), moderate (ie, respiratory symptoms and fever with pneumonia), severe (ie, respiratory distress, respiratory frequency ≥30/min, blood oxygen saturation ≤93%, ratio of partial pressure of arterial oxygen to fraction of inspired oxygen <300 mm Hg, and/or lung infiltration >50% within 24-48 hours), and critical (ie, respiratory failure, shock, and/or multiple organ dysfunction or failure).

The discharge criteria were normalisation of body temperature for more than 3 days, obvious improvement of respiratory symptoms, pulmonary imaging showing distinct inflammation absorption, and two consecutive negative nucleic acid tests on respiratory tract samples such as sputum or nasopharyngeal swab (with a sampling interval of at least 24 hours). Patients with COVID-19 who met the above criteria could be discharged.

We used SPSS (Windows version 19.0; IBM Corp, Armonk [NY], US) for all statistical analyses. One-way analysis of variance was performed to compare continuous, normally distributed numeric variables, which were presented as means and 95% confidence intervals. The Mann-Whitney U non-parametric test was used to compare continuous numeric variables with skewed distributions, which were shown as medians and 95% confidence intervals. The Pearson χ² test was employed to compare categorical variables, which were presented as frequencies and proportions (percentages). A stratified analysis by age was also conducted. Comparative analysis between early and late discharge was implemented to explore potentially associated factors. A P value of <0.05 was considered to be statistically significant.

Among these 96 patients with COVID-19, six were aged 0 to 18 years and 14 were aged >60 years (Table 1). Most (79.2%) patients were aged between 19 and 60 years. No significant sex difference was discovered. All patients had basically normal body mass index values. Half of patients aged >60 years had a history of hypertension. Eight adult patients had a surgical history involving pituitary tumour, pulmonary abscess, coronary artery bypass grafting because of coronary heart disease, gallbladder stone, ovarian cyst, Caesarean section, or splenectomy because of trauma. Other co-morbidities were exclusively observed in patients aged >40 years, including type 2 diabetes mellitus, fatty liver, hepatitis B, liver cirrhosis, and bronchiectasis. A history of smoking or drinking was reported by nine (9.4%) and 10 (10.4%) patients, respectively.

Among 96 patients with confirmed infection, 28 (29.2%) had travelled from Wuhan City, and 51 cases were acquired via close contact. However, a few patients had no definitive contact history, even after rigorous tracing. Familial clusters of the disease accounted for 48 of this study’s cases, and 11 patients who had travelled from Wuhan City presented in familial clusters. In most familial clusters, two members were attacked, however, six family members were also found to be infected in two separate familial clusters.

The mean time from symptom onset to the first visit was 3.7 days, and the time to hospital admission was 4.5 days. The period from symptom onset to definitive diagnosis based on positive viral nucleic acid test was 5.2 days. The mean incubation time was 7.0 days. The mean time with fever before admission was 3.3 days, and the maximum body temperature before admission was 37.9°C.

The laboratory-confirmed patients’ main symptoms were fever, cough, fatigue, sore throat, chills, expectoration, shortness of breath, headache, dizziness, decreased appetite, diarrhoea, nausea, and vomiting (Table 2). These symptoms essentially involved the respiratory system, in addition to the alimentary and central nervous systems. The symptoms were basically similar across different age-groups, except that shortness of breath occurred more commonly among patients aged >60 years.

As presented in Table 3, the mean white blood cell count was not elevated. Besides white blood cells, the levels of haemoglobin, eosinophil, and platelets were basically within normal ranges. Lymphocytopenia was observed predominantly in patients aged >60 years. The concentrations of blood electrolytes, glucose, lactate, triglycerides, and free fatty acids were largely normal. Injury to the liver, kidney, heart, and coagulation systems were not observed. Further, hypoxaemia was not found in most cases on hospital admission, except for several patients aged >60 years. The overall ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen was about 340 mm Hg. Inflammatory biomarkers are an acute-phase response to the virus insult and are therefore involved in the development of the disease. Generally, the level of blood C-reactive protein was slightly elevated on admission (16.2 mg/L), and that of patients aged >60 years was relatively higher (31.6 mg/L). Serum amyloid A concentration increased in almost all cases (61.7 mg/L), especially for patients aged >60 years (88.1 mg/L). The procalcitonin level did not increase across all cases on admission.

During hospitalisation, eight patients with COVID-19 were transferred to a designated provincial hospital in Hangzhou to enact an optimal allocation policy. Therefore, we analysed the clinical and laboratory features of 88 cases during hospitalisation (Table 4). The severity of disease was mild or moderate in 83 patients (around 94%). Among 12 patients aged >60 years, three (25%) had severe disease. The mean length of stay across all cases was 15.6 days. The mean time with fever during hospitalisation was 4.4 days. The mean maximum body temperature was 37.8°C. Hypokalaemia, hyponatraemia, and hypoalbuminaemia were more likely to develop in patients aged >60 years. The time from symptom onset to secondary negative result of a viral nucleic acid test was about 17 days, and the mean time to patient discharge was about 20 days.

Most cases (59.1%) were supported through nasal catheter or mask oxygen. No one was assisted by non-invasive or invasive mechanical ventilation. All patients were treated with one or two kinds of antivirals, ie, α-interferon, lopinavir/ritonavir, or abidor. Antibiotics like levofloxacin and moxifloxacin were prescribed when bacterial infection was suspected. Adjuvant therapy with glucocorticoids (methylprednisolone, 40-80 mg/d) or γ-globulin was implemented only in a small percentage of cases (around 10%) and exclusively in adult patients. All patients successfully recovered and were discharged. No one progressed to the critically ill state, and the absence of recurrence in all cases was confirmed by follow-up until 20 June 2020.

Radiological pulmonary imaging was evaluated during hospitalisation of the patients with moderate and severe disease (74 cases) [Table 5 and Fig]. A total of 19 (25.7%) and 55 (74.3%) patients presented with unilateral and bilateral pulmonary lesions, respectively. Ground-glass opacities in the lungs were discovered on chest CT scan in approximately 50% of cases. Radiological pulmonary changes were mostly distributed in the subpleural area (around 80%), and pleural effusion rarely occurred in any age-stratified group. The mean time from symptom onset to the worst CT imaging finding was 9 days, and the mean time to the start of pulmonary infiltration absorption on CT imaging was about 12 days.

We explored the factors that could potentially be associated with early discharge of patients with COVID-19 (Table 6). Early discharge was defined as a hospital length of stay (LOS) of ≤10 days. A comparison was conducted between early (LOS ≤10 days) and late (LOS >10 days) discharge of patients with COVID-19. Of the investigated patients, 20 cases were discharged early, whereas 68 cases underwent late discharge. We compared 13 factors between the two groups. Two factors were significantly associated with early discharge: more patients in the early discharge group compared with the late discharge group had travelled from Wuhan City (50.0% vs 22.1%). Further, the time from symptom onset to secondary negative result of a viral nucleic acid test was shorter in the early discharge group than the late discharge group (11.8 days vs 18.7 days).

The emergence and spread of COVID-19 has caused a new public health crisis to threaten the world. Patient zero of the disease is still unknown, although many of the initial cases in Wuhan City had exposure to the Huanan Seafood Wholesale Market in common.4 5 A probable bat origin of SARS-CoV-2 has been considered.6 Angiotensin-converting enzyme II has been reported to be the entry receptor on epithelial and endothelial cells within the lung, heart, kidney, and intestine.6 7 As a highly contagious disease, COVID-19 is transmitted by inhalation or contact with infected droplets. On 23 January 2020, Wuhan City, as the epicentre of COVID-19 in China, was locked down to prevent the disease’s spread. Before the lockdown, some infected people left Wuhan City for other cities outside Hubei Province. Then, extensive person-to-person transmission occurred.8 9 Thanks to healthcare service providers, all hospitalised patients with COVID-19 in our research survived, recovered successfully, and then were eventually discharged. The findings of our observational study can provide help with decision making about public health policy involving COVID-19 prevention and therapy.

This retrospective study reports the epidemiological, demographic, clinical, laboratory, and radiological findings of patients with COVID-19 who were treated at a designated hospital in Hangzhou City. A comparative analysis according to age stratification was implemented. Deterioration was more probable in patients aged over 60 years with underlying co-morbidities. The finding is consistent with those of another previous report.10 Deterioration could be associated with the ageing and dysfunction of organs, especially reduced immune function as lymphocytopenia. Severe acute respiratory syndrome coronavirus 2 can consume lymphocytes, which is probably an important cause of the proliferation and spread of the virus. Although we did not detect the plasma levels of pro-inflammatory mediators like tumour necrosis factor and interleukin, the cytokine storm has been previously reported to be associated with COVID-19 severity.11

Respiratory symptoms like fever, cough, sore throat, and shortness of breath were commonly the first presentations during hospital visits among the patients in the present study. The disease should be differentiated from influenza and common cold-causing rhinovirus or parainfluenza virus infections. In the early stage of the pandemic, a policy of selfisolation and home quarantine was implemented. However, because of the high contagiousness of SARS-CoV-2, 50% (48 of 96) of the cases in our study appeared as familial clusters. Prior studies also reported the discoveries of case clusters within familial households.12 13 14 The basic reproductive number (R0) has been revealed to be as high as 2.2 or even 5.7.15 16 Therefore, strict control measures should be implemented to avoid intrafamilial dissemination during self-isolation and home quarantine.

The disease has very strong infectivity by human-to-human transmission, even during the incubation period. Based on the gradually increasing understanding of the disease’s characteristics, the policy for personnel travelling from the epidemic area to Hangzhou City was changed from self-isolation and home quarantine to centralised compulsory isolation on 21 March 2020. Consequently, person-to-person transmission was effectively controlled. Therefore, strict quarantine has been confirmed to be the only effective intervention to decrease the contagion rate.

Early negative turning of the viral nucleic acid test was associated with early discharge of patients with COVID-19 in this study. This may imply early recovery of injured organs. A relatively high proportion of patients who travelled from Wuhan City were discharged early. Thus, SARS-CoV-2 could have mutated and evolved. More research is needed to clarify that whether its virulence has increased or decreased after its propagation through generations.

In this study, five (5.7%) patients had the severe disease type, but no patients died. In a summary report from Chinese Center for Disease Control and Prevention with data updated through 11 February 2020, 14% of 44 415 confirmed cases were classified as severe, and 5% were critical.13 The overall case-fatality rate was 2.3% (1023 of 44 672 confirmed cases). In Italy, the corresponding rate was reported to be 7.2% (1625 deaths of 22 512 cases) based on data through 17 March 2020.17 The case-fatality rate of COVID-19 is much lower than those of the prior SARS and Middle East Respiratory Syndrome, which were 9.6% and 34.4%, respectively.13 However, because of the shortage of PCR test kits and the existence of false-negative PCR results, the actual number of cases in the population is unknown. Serological tests, when available, could be adopted widely in the future for COVID-19 diagnosis. Although the quantity of cases in this study is limited, overall recovery from the disease will proceed well when diagnosis and treatment are conducted early and properly, if overcrowding of medical resources is avoided.

Bilateral distribution of patchy shadows and ground-glass opacities in the subpleural area were the most frequently discovered radiological findings in the present study, and these are typical hallmarks of radiological pulmonary imaging in COVID-19.18 Although multiple organs (eg, those of the respiratory, alimentary, genitourinary, and central nervous systems) can interact with SARS-CoV-2 owing to viraemia and the cytokine storm, the lungs are still the principal target of the virus. Generally, the pulmonary presentation is consistent with the clinical severity of COVID-19. Because there were no critical cases in our study, more severe chest imaging findings were not present (eg, entire lungs involved in exudation and consolidation). Certain critical patients in intensive care units with severe acute respiratory distress syndrome even need extracorporeal membrane oxygenation support.19 In epidemic areas, chest CT could also be adopted as an early supplementary diagnostic tool.20

So far, there is no specifically proven antiviral treatment for COVID-19. The mainstay of therapy is optimised supportive care, including proper oxygen supply. The efficacy of antiviral drugs, including lopinavir/ritonavir, is still unknown.21 The pharmacotherapies used in the present study, including antiviral and immunomodulating treatments, are only empirical and palliative. Further randomised clinical trials are urgently needed to determine the most effective evidence-based treatments.

The current study has several limitations. First, this is a retrospective study with data from a single centre. The number of included cases is relatively small. However, it is meaningful for the evaluation of characteristics of early cases outside of Wuhan City, especially for policy makers. Second, no potentially effective antiviral drugs can be proposed by the present study. Further basic and clinical research is required to elucidate effective and safe pharmacotherapies, as to date, no proven antiviral drugs are available. Third, asymptomatic infection of COVID-19 is currently an important issue. We do not have enough data to provide associated information. More studies are needed to provide diagnosis and differentiation of asymptomatic cases, particularly involving the serological and nucleic acid tests that have recently become available to the general population.

During the early stage of the COVID-19 outbreak, half of the patients from a designated hospital in Hangzhou City were discovered as familial clusters. Therefore, strict prevention and control measures should be implemented during self-isolation. Patients aged >60 years with underlying co-morbidities were prone to lymphocytopenia and severe infection.

Concept or design: J Gao, S Zhang.
Acquisition of data: K Zhou, X Zhao, J Liu.
Analysis or interpretation of data: J Gao, Z Pu.
Drafting of the manuscript: J Gao, Z Pu.
Critical revision of the manuscript for important intellectual content: S Zhang, K Zhou, X Zhao, J Liu.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

All authors thank all of the patients with COVID-19 and healthcare service providers at XiXi Hospital of Hangzhou, China.

This research was supported by the Innovative Talents Supportive Project from Medical Health Science and Technology Programme of Zhejiang Provincial Health Commission, China (Ref 2020RC072). The funder had no role in study design, data collection/analysis/interpretation, or manuscript preparation.

The study was approved by the Ethics Committee of the XiXi Hospital of Hangzhou, China (Ref 2020-31). The requirement for informed consent was waived because of the retrospective nature of this study.

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