Abstract

Recently, the outbreak of Corona Virus Disease 2019 (COVID-19) originating in Wuhan has rapidly spread across China and beyond, with especially severe epidemic in cities around Wuhan. We report the epidemiological and clinical futures of the 200 patients infected with COVID-19 in Yichang, Hubei Province, China. A total of 200 patients confirmed with COVID-19 in a designated hospital in Yichang from Jan 30 to Feb 8,2020 were investigated retrospectively. The epidemiological data, demographic data, comorbidities and clinical manifestations, laboratory tests, chest CT scans, treatment and clinical outcomes were collected. The data between patients admitted to the intensive care unit (ICU) and those not in the intensive care unit were compared. The patients were followed up until Feb 26, 2020.The Corona Virus Disease 2019 (COVID-19) infection was of clustering onset, and can cause severe respiratory disease and even death, especially for elderly patients with chronic disease. The mortality of ICU patients confirmed with COVID-19 was considerably high. The lymphocytes, especially T lymphocytes might be the main target of Corona Virus Disease 2019 (COVID-19) and related to the severity and mortality of disease, and the cytokine storm may be associated with the worsening of the disease

Keywords: Pneumonia; Epidemiology; Clinical Features; Hospitalized Patients; 2019- nCoV

Abbreviations: CT: Computed Tomographic, MERS: Middle Eastern Respiratory Syndrome, SARS: Severe Acute Respiratory Syndrome, CDC: Center for Disease Control and Prevention

Introduction

In December 2019, a new pneumonia case of unknown etiology emerged and began to widely spread in Wuhan, Hubei Province, China. Most of the patients were epidemiologically linked to the Huanan Seafood Wholesale Market, indicating animal-to-human disease transmission mode, but soon there was considerable evidence to confirm the human-to-human transmission [1,2]. Within two weeks after the outbreak, the Chinese Center for Disease Control and Prevention (CDC) isolated samples from lower respiratory tract for deep sequencing analysis, suggesting a novel coronavirus, which was officially named SARS-CoV-2 by WHO on Feb 11, 2020. Since the SARS-CoV-2 has typical characteristics of the coronavirus family, it is currently classified in the lineage B beta coronaviruses that also include Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) [3-6]. Although the source of the SARS-CoV-2 is still under investigation, genome sequencing and phylogenetic analysis proved that the sequence of RNA genome of the virus is similar to bat coronaviruses, indicating the bats maybe the primary source [7].

The disease caused by the SARS-CoV-2 was officially named Corona Virus Disease 2019 (COVID-19) by WHO [8]. Previous studies showed that the clinical manifestations of patients with COVID-19 in Wuhan mainly included fever, chill, cough, difficulty in breathing, muscle soreness, fatigue, as well as complications such as acute respiratory distress syndrome (ARDS), acute kidney injury, and acute cardiac injury, etc [9]. Laboratory tests showed that the leukocytes were normal or decreased, and/or the lymphocytes decreased. And the chest imaging revealed typical features of viral pneumonia [10]. Wang et al reported that among the 138 investigated patients, 36 received ICU care, with the mortality of 4.3%. It was found that the COVID-19 was of clustering onset, and the older men with comorbidities were more likely to develop into critically ill patients [11]. Although the government adopted a series of measures to respond to this major public health emergency, such as prohibiting from leaving or coming into Wuhan and group activities, in the following dozens of days, a large cluster of the pneumonia rapidly spread throughout China and beyond. And the epidemic was especially severe in cities around Wuhan in Hubei Province. As of Feb 26, 2020, there were 78630 confirmed COVID-19 cases, 2358 suspected cases, 32531 cured cases, and 2747 deaths in China, of which 65596 were confirmed cases in Hubei Province and 929 were confirmed cases in Yichang City, which owns huge economic development potential in Hubei Province, second only to Wuhan[12,13].
So far, there have been several studies that have summarized and analyzed the epidemiological and clinical features of pneumonia caused by SARS-CoV-2 in Wuhan [14-16]. However, the information on the epidemiological and clinical features of COVID-19 in other areas is scarce. The main purpose of this study was to comprehensively analyze and compare the epidemiological, clinical, laboratory, radiological, treatment, and outcome data of confirmed patients with COVID-19 admitted in a designated hospital in Yichang, Hubei Province, China. We hope our findings can provide some references for understanding the epidemics and clinical characteristics of this novel coronavirus outside Wuhan.

Materials and Methods

Sample Collection

200 patients with confirmed COVID-19 were recruited from Jan 30 to Feb 08, 2020 at Yichang Central People’s Hospital, a designated hospital in Yichang, Hubei Province, China. Patients throughout Yichang City were centrally admitted to the hospital without selectivity. All the enrolled COVID-19 patients in this study were diagnosed according to WHO interim guidance. The study was approved by the Ethics Committee of Yichang Central People’s Hospital and written informed consent was obtained from the enrolled patients.

Procedures

The epidemiological, clinical, laboratory, treatment, and outcome data of the patients were obtained from electronic medical records. All the data were reviewed by two physicians (LH Yang and R Zhang).The information included demographic data, family clustering (≥2 infected family member),exposure history (living in or visiting Wuhan or contact with people from Wuhan ≤14 days before infection), comorbidities, clinical manifestations (symptoms and signs), laboratory tests, chest Computed Tomographic (CT) scans, treatment (ie, medical treatment, respiratory support, renal replacement therapy), and outcomes (complications, including death). Throat-swab samples from the upper respiratory tract were collected during hospitalization. SARS-COV-2 was detected by real-time polymerase chain reaction (RT-PCR) following the recommended protocol. Infection was confirmed when there were at least 2 positive results.

Outcomes

We described and summarized demographic data, family clustering, exposure history, potential comorbidities, clinical manifestations, laboratory tests, chest CT scans, treatment measures, and prognosis.

Statistical Analysis

All statistical analyses were performed using SPSS20.0 version software. Continuous variables were represented as mean, median, and Interquartile Range (IQR) values. Independent group t-test was used to compare the means of continuous variables when the data were normally distributed. Categorical variables were represented as frequency and percentage. The Mann-Whitney test was used when the data were non-normally distributed. Chi-square test was used to compare proportions of categorical variables, although Fisher’s exact test was used in cases where data was limited. A twosided α of less than 0·05 was considered statistically significant.

Result

A total of 200 patients with laboratory-confirmed COVID- 19were enrolled in the study. Among them, 98(49.0%) were male and 102(51.0%) were female, with the mean age of 55 years (SD 17.1 years). Three children and two pregnant women were infected. Of the 200 patients,29 (14.5%) were admitted to the ICU because of the requirement of high-level oxygen support measures or the development of organ dysfunction, and the remaining 171 (85.5%) were admitted to isolation wards. The age of ICU patients (mean age 71 years, SD13.4) was older than the non-ICU patients (mean age 52 years, SD 16.2, P=0.000). About two thirds of the patients came from Xiling District of Yichang City. Of these patients,24(12.0%) had a history of residing in or visiting Wuhan within 2 weeks before infection, 89(44.5%) had an intensive contact with visitors from Wuhan or confirmed COVID-19 patients, and the remaining 87 (43.5%) had no linkage to Wuhan or contact history. Familial clustering was found in 34 patients, accounting for 17%. Among the 200 patients, 65(32.5%) suffered from 1 or more comorbidities, with hypertension (45[22.5%]), diabetes (21[10.5%]) and chronic heart disease (11[5.5%]) as the top three common coexisting conditions (Table 1).

Most patients had fever (171[85.5%]) and cough (116[58.0%]) on admission. And some patients had fatigue (64[32%]), myalgia and malaise (44[22%]), dyspnea (29[14.5%]), chills or rigors (34[17%]), headache (27[13.5%]) and sore throat (26[13%]). Other symptoms included diarrhea (14[7%]), nausea and vomiting (4[2%]). Compared with the patients admitted to the isolated wards, patients who received ICU care were more likely to show dyspnea, nausea and vomiting. In addition, 6 patients with non- ICU care were asymptotic, all of whom found lung imaging changes after having epidemiological exposure history. The median time from illness onset to first admission was 5 days (IQR 2.25-7.0). On admission, the leucocytes of most patients were below or within the normal range. And most patients had lymphopenia, with the median level of 0.91×109/L (IQR,0.69-1.22).There were significant differences in the median value of lymphocytes and the proportion of lymphopenia between patients with ICU care and those with non-ICU care (0.73×109/L [IQR,0.56-0.89]vs 0.94×109/L [IQR, 0.73-1.26], P=0.000; 25 [86.2%] vs 112 [65.5%], P=0.026). The C-reactive protein and D-dimer were higher in ICU patients than non-ICU patients median C-reactive protein level 68.8mg/L [IQR, 53.47–108.25] vs 18.7 mg/L [IQR,6.3-37.9],P=0.000; median D-dimer level 1.1mg/L[IQR, 0.6-1.8] vs 0.5mg/L[0.3-0.7],P=0.000.
The incidences of ALT and AST above the normal range in ICU patients were higher than those in non-ICU patients (41.4%vs 18.7%, P=0.006;58.6%vs 33.3%, P=0.009). 57(28.5%) patients had different degrees of kidney dysfunction, with serum creatinine above the normal range. 77 (38.5%) patients showed an elevation of lactate dehydrogenase, of whom 22 belonged to the 29 ICU-patients (81.5%). The Procalcitonin was increased in 25 (86.2%) of ICU patients, higher than the non-ICU patients (23[13.5%], P<0.001). According to chest CT on admission,176 (86%) patients had bilateral involvement (Table 2). Many of the patients presented with complications, including 32(16%) with acute respiratory distress syndrome (ARDS), 10(%) with acute cardiac injury, 24(12%) with acute renal injury,12(6.0%) with secondary infection, and 4(2%) with shock (Table 3). And it was found that the complications were more common in the ICU patients than in the non-ICU patients.199(99.5%) of the 200 patients were treated with antiviral therapy (Abidol, Oseltamivir, Lopinavir/ritonavir), and 141(70.5%) received antibiotic treatment (Moxifloxacin, Ceftriaxone). More than half of the patients (112[56%]) received corticosteroid therapy. 2 patients (2[1%]) were treated with continuous renal replacement therapy (CRRT). All patients received oxygen support on admission. Most patients (24[82.8%]) in the ICU received high flow oxygen or noninvasive ventilation. 14 patients (48.3%) required invasive mechanical ventilation to relieve hypoxemia.

In the non-ICU wards, high flow oxygen or noninvasive ventilation was required in 11 patients (9.9%), two of whom received invasive mechanical ventilation with the worsening of the disease. As of Feb26, 2020, 42 (21%) of 200 patients had been discharged including two children and 16(8.0%) patients had died. Of the 29patients in the ICU, 12were still hospitalized, 3 had been discharged and15 had died. Through analyzing and tracking laboratory results of the patients who had died, we found that the neutrophils, PCT, IL-6 and CRP were 14.2×109/L(SD 8.4), 4.49 ng/ ml (IQR 1.57-25.8), 248.85 pg/ml (IQR,77.54-1671.3) and 105.7 mg/L(IQR 82.7-220.1) before they died, which were significantly higher than the normal range. The main imaging findings included bilateral mottling and ground glass opacity, multiple lobular or subsegmental areas of consolidation (Figure1). And all the 200 cases of SARS-CoV-2 infection were confirmed by RT-PCR.

Conclusion

Discussion

Here in, we reported a total of 200 patients with confirmedCOVID-19. The 200 patients were admitted to the designated hospital in just 10 days from Jan 30, 2020 to Feb 8,2020, indicating the outbreak of the COVID-19 in Yichang, China. Meanwhile, the local government actively adopted public health outbreak response tactics, including quarantine, isolation, school closure, social distancing, and community containment, etc. As of Feb 23, 2020 in Yichang, 924 caseswereconfirmed,304 cases were cured, and 29 cases were dead, with the case fatality rate of 3.14%. While according to the latest study by Xb Yang and his colleagues, the case fatality rate of critically ill patients with COVID-19 at 28 days was 61.5%, which was very considerable. Similarly, during our 28-day follow-up after admission in our study, 15 of the 29 ICU patients had died, and the case fatality rate in the ICU was as high as 51.7%.Our study also found that the population was generally susceptible to the virus, and the older patients with comorbid conditions usually developed into critically ill cases with many complications and required ICU admission.
As mentioned in the previous section, many patients came from Xiling District of Yichang City, which may be related to the fact that some residents of the area worked in Wuhan. Through the epidemiological survey, only 24(12.0%) were founded to have a history of Wuhan residence or travel within 14 days before onset of illness. Almost half of the patients had no linkage to Wuhan or contact history. This suggests the human-to-human transmission and highly contagiousness of the SARS-COV-2. At present, the main transmission routes of SARS-COV-2 are proved to be droplet transmission and contact transmission, with the possibility of aerosol transmission in prolonged exposure to high concentrations of aerosol in a relatively closed environment. Finding out the transmission routes can help to prevent the spread of the SARSCOV- 2 more effectively [17]. Similar to those infected with beta coronaviruses such as SARS-CoV and MERS-CoV, most patients with SARS-CoV-2 infection presented with fever, cough, fatigue, dyspnoea, and bilateral ground-glass opacities and patchy shadows on chest computed tomography. Sore throat, headache, diarrhea, nausea and vomiting occurred in a few patients infected with SARSCoV- 2 [18]. In addition, 6 people were asymptomatic. As for the laboratory tests, the lymphocytes of most patients were below the normal range, and the lymphocytes in ICU patients were less than those in non-ICU patients. This result suggests that lymphocytes, especially T lymphocytes might be the main target of SARS-CoV-2 and related to the severity and mortality of disease. Z Xu and his colleagues showed the T cells were excessively activated while the counts were substantially reduced by autopsy of a patient with COVID-19 [19]. Moreover, our study also found that the neutrophils, PCT, IL-6 and CRP of the 14 patients who had died were significantly higher than the normal range, suggesting that the cytokine storm maybe associated with disease. Virus particles penetrate the respiratory mucosa and activate lymphocytes, then induces forms a cytokine storm, which causes severe immune damage to the lungs and other organs [20,21]. However, the specific pathophysiology of COVID-19remains to be further explored.
At present, some effective treatment methods for COVID-19 have been summarized based on clinical practice [22-24]. The antiviral drugs for COVID-19 in clinic curently mainly includeα- interferon aerosol inhalation, Lopinavir / ritonavir, Ribavirin, Chloroquine phosphate and Abidol [25]. And the antibiotics should be used cautiously [26]. If the patient has dyspnea and chest imaging progress, glucocorticoids can be used within a short period of time (3 to 5 days) with the dose not exceeding 2 mg / kg / day of methylprednisolone [23]. Other treatments include respiratory support, traditional Chinese medicine treatment, the plasma treatment of rehabilitation patients, extracorporeal blood purification technologies such as plasma exchange, adsorption, perfusion, and hemofiltration. And a vaccine against SARS-CoV-2 is being under development.
There are still some limitations in this study. First of all, this study only included patients admitted to Yichang Central People’s Hospital, which might not fully represent all the patients in the city. Multi-center collaborative studies with larger sample size in the future are required. Secondly, throat swab specimens were used to diagnose COVID-19 by RT-PCR. However, specimens collected from the upper respiratory tract may lead to false negatives, thus leading to missed diagnosis and pseudo-cure cases. The viral load and viral antigen in blood can be detected to provide better assessment of the condition. Thirdly, many patients are still hospitalized at the time of manuscript submission, and the outcomes at present may not fully reflect the prognosis of all patients with COVID-19.

Conclusion

In conclusion, of the 200 patients infected with COVID-19in Yichang, China,14.5% of patients were admitted to the ICU, who were mainly older patients with comorbidities and ARDS. And the mortality of confirmed patients in the ICU was high.

Acknowledgment

We thank all participating patients and their families, as well as staffs of all the institutions involved in this study.

Contributors

Luhuan Yang and Yunhong Leicontributed equally. Luhuan Yang had the original idea, designed the study with Yunhong Lei, and drafted the manuscript, Luhuan Yang Rong Zhang,Jinglan Liu and Qiong Liu collected and summarized the epidemiological and clinical data, Jun Yang and Yunhong Lei revised the final manuscript, Mingwu Li,Xiaojing Zhou,Chuangjun Hu and Zifeng Li retrieved the document about the virus.

Declaration of Interests

We declare no competing interests

ORCID

Luhuan Yang https://orcid.org/0000-0002-8868-9193
Yunhong Lei https://orcid.org/0000-0003-4838-2709

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Abstract

Recently, the outbreak of Corona Virus Disease 2019 (COVID-19) originating in Wuhan has rapidly spread across China and beyond, with especially severe epidemic in cities around Wuhan. We report the epidemiological and clinical futures of the 200 patients infected with COVID-19 in Yichang, Hubei Province, China. A total of 200 patients confirmed with COVID-19 in a designated hospital in Yichang from Jan 30 to Feb 8,2020 were investigated retrospectively. The epidemiological data, demographic data, comorbidities and clinical manifestations, laboratory tests, chest CT scans, treatment and clinical outcomes were collected. The data between patients admitted to the intensive care unit (ICU) and those not in the intensive care unit were compared. The patients were followed up until Feb 26, 2020.The Corona Virus Disease 2019 (COVID-19) infection was of clustering onset, and can cause severe respiratory disease and even death, especially for elderly patients with chronic disease. The mortality of ICU patients confirmed with COVID-19 was considerably high. The lymphocytes, especially T lymphocytes might be the main target of Corona Virus Disease 2019 (COVID-19) and related to the severity and mortality of disease, and the cytokine storm may be associated with the worsening of the disease

Keywords: Pneumonia; Epidemiology; Clinical Features; Hospitalized Patients; 2019- nCoV

Abbreviations: CT: Computed Tomographic, MERS: Middle Eastern Respiratory Syndrome, SARS: Severe Acute Respiratory Syndrome, CDC: Center for Disease Control and Prevention