Clinical characteristics of hospitalized patients with COVID-19 in Yueyang, Hunan, China

The clinical characteristics of patients with novel coronavirus disease (COVID-19) in Hunan Province are less understood. We analyzed retrospectively the epidemiological, clinical characteristics, and risk factors associated with severity of 113 conrmed COVID-19 cases in Yueyang, Hunan Province, China, from January 20, 2020, to March 8, 2020, and followed until April 13, 2020. Of the 113 conrmed cases, 92 (81.4%) were from or infected by patients from Hubei province. More than half (63) of patients with COVID-19 had no fever in the early stages of disease. 23% patients had no symptoms at the onset. As of March 8, 2020, 113 (100%) of 113 patients had met the discharge criteria, 0 (0%) patients died. Compared with the non-severe cases, severe cases were associated with older age or patients with comorbidities, secondary bacterial infections, and higher levels of C-reactive protein. Longer duration of virus clearance was associated with a higher risk of progression to critical status. Older patients or patients with comorbidities such as diabetes were more likely to have severe condition. Prompt and effective treatment and sucient medical resources may still signicantly reduce hospital-related transmissions and mortality.


Introduction
In December 2019, a series of cases of pneumonia with unknown cause, now known as Corona Virus Disease 2019 (COVID- 19), had been reported in Wuhan, China 1 . Soon after, other areas across the country reported outbreaks, and as of April 29, 2020, a total of 82,862 COVID-19 cases in China have been con rmed with 4633 deaths 2 . Unfortunately, the number of infections and deaths is still increasing in the rest of the world [3][4][5] .
At present, information regarding the epidemiological, clinical characteristics, and risk factors of COVID- 19 in Hunan province is limited. Yueyang, adjacent to Wuhan, is the second largest prefecture-level city in Hunan province with a population of 5.77 million. There are a large number of people working and studying in Wuhan. Therefore, Yueyang has become one of the main epidemic areas of imported cases. In a retrospective study from Wuhan, the estimated mortality rate was 1.1% for non-critical patients and 32.5% for critical patients 6 . Another report from the city analyzed the clinical characteristics of 138 hospitalized patients with COVID-19 in Wuhan. They reported 26% of patients received ICU care and the mortality rate was 4.3% 7 . However, these studies may not represent the realities in the cities outside of Wuhan.
This study describes the epidemiological, clinical characteristics, and risk factors associated with severity of 113 con rmed COVID-19 cases in Yueyang, Hunan Province.

Results
Demographic and clinical characteristics A total of 113 patients with con rmed COVID-19 were included in the study. The demographic and clinical characteristics were summarized in Laboratory and radiographic ndings on admission As shown in Table 2, lymphocytes (P = 0.001) and white blood cell (p = 0.041) were signi cantly decreased in severe patients. Compared with non-severe patients, the C-reactive protein (CRP, p < 0.001), procalcitonin (PCT, p = 0.001) and lactate dehydrogenase (LDH, p = 0.027) were signi cantly increased in severe patients. No signi cant differences in serum biochemical indexes of the liver (ALT and TBIL) and kidney (BUN and Cr), hemoglobin (HGB), platelet count (PLT), erythrocyte sedimentation rate (ESR) and Ddimer were observed between severe and non-severe patients at admission. Of the chest CT images of the 113 patients, 17 (15%) had no change, 75 (66.4%) were mild, 15 (13.3%) were in advanced stage, and 6 (5.3%) were severe on admission. Figure 1 is a typical patient's chest CT from mild to severe stages.  Disease progression, complications, treatment and clinical outcomes As shown in Table 3, the duration of fever (7 vs 2, p = 0.02), days from symptom onset to virus clearance (24 vs 15.5, p < 0.001), days from symptom onset to pneumonia resolution (28 vs 17, p <0.001) and length of hospital stay (21 vs 11, p < 0.001) were longer among severe patients than non-severe patients. In the hospitalization and follow-up period, the complications of COVID-19 were assessed, including secondary bacterial infections (8%), pulmonary brosis (2.7%) and acute respiratory distress syndrome (ARDS) (8%). All the above-mentioned complications were more common in 11 severe cases, compared with non-severe cases (all P<0.05). Antiviral drugs were used speci cally to treat COVID-19 during hospitalization, including lopinavir/ritonavir (77.9%), arbidol (90.3%), oseltamivir (39.8%) and chloroquine (10%). For severe cases, methylprednisolone (1-2 mg/kg/d) for 3-5 days combined with human gammaglobulin (10-20 g/d) was prescribed. Seven patients received ICU care, and 3 cases received invasive mechanical ventilation. Interferon inhalation was used in almost all patients. As of March 8, 2020, 113 (100%) of 113 patients had met the discharge criteria. 0 (0%) patients died.

Factors affecting virus clearance
In order to assess factors affecting virus clearance, duration of virus clearance is converted into an ordered variable: ≤15d, 15-30d, >30d. The Kruskal-Wallis test found that the rate of patient progress to severe clinical condition was correlated with the duration of virus clearance (P = 0.0025), as shown in Figure 2. In ordered logistic regression model, comorbidity was the only independent prognostic factor of viral clearance (OR 4.85; 95% CI 1.11-22.07, P = 0.037) ( Table 5). Abbreviations: L, lymphocyte count; CRP, C-reactive protein; LDH, lactate dehydrogenase.

Discussion
Data on COVID-19 in Hunan province are very limited. This study provided a comprehensive data on the demographic, epidemiological, laboratory, and radiological characteristics as well as the comorbidities, treatment, and outcomes of inpatients with non-severe and severe COVID-19 in Yueyang, Hunan province. 11 (9.7%) patients in this study were identi ed as severe cases and mortality was 0%, which differ from the results of Wuhan 1,6,7 .
Of the 113 con rmed cases, 92 (81.4%) were from or infected by patients from Hubei province, which indicate the importance of disease control measures, especially in the case of peak numbers in areas such as Wuhan, in order to prevent ongoing transmission and contact with close contacts. Severe patients were older and had comorbidities such as diabetes more often than non-severe patients. Therefore, high-quality medical treatment should be given priority to older patient. As shown in the previous studies 7 , there were no gender difference between severe and non-severe patients in our study.
For SARS patients, fever was almost always the rst clinical symptom commonly 13 . However, our data showed more than half (63) of COVID-19 patients had no fever in the early stages of disease. This means that screening a population using a thermometer alone is not enough, and that screening criteria should include other indications.
In previous retrospective study of  in Wuhan City 1 , nearly 1/3 of patients were admitted to the intensive care unit (ICU). In our study, the patients presenting to the hospital were mostly non-severe (90.3%) cases. Although the rate of progression from non-severe to severe cases is not as high as that of SARS or MERS (ranging from 70% to 90%) 14,15 , prompt and effective treatment may still signi cantly reduce hospital-related transmissions and mortality.
According to the suggestion of Diagnosis and Treatment of COVID-19 (version 7) 10 , all of the patients in this study received antiviral therapy (lopinavir/ritonavir or arbidol), aerosol inhalation of interferon-alpha and traditional Chinese medicine treatment. Until now, all treatments have relied on meticulous supportive care and improved immunity. Speci c antiviral drugs for COVID-19 are being developed, but this process may take time. In addition, among our cohort of 113 con rmed patients with COVID-19, glucocorticoid was used in 1% of non-severe patients and 81.8% of severe patients. However, the use of glucocorticoid remains controversial. One study showed that clinical evidence did not support glucocorticoid therapy for COVID-19, nor did the bene ts of glucocorticoid-supported therapy be observed 16 . Risk factors for severity identi ed in this study included secondary bacterial infections, duration of virus clearance and CRP, consistent with those in previous reports 6,17,18 . However, different from previous studies 19 , our logistic regression analysis results showed comorbidity was identi ed as an independent risk factor for viral clearance.
Our study had several notable limitations. First, since this was a single-center retrospective study, the results could not be generalized. Second, because some severe patients were directly transferred to provincial medical institutions for treatment, only a few severe patients were monitored in this study. Additionally, the long-term complications of COVID-19 could not be fully assessed due to limited study time.
The median for continuous variables were compared by using Mann-Whitney test. Unordered categorical variables were compared using the chi square test, and the Fisher exact test was used when the sample was limited. Kruskal-Wallis test was used to compare ordered categorical variables across groups.
Multivariable binary stepwise logistic regression analysis was used to assess risk factors associated with progression to severity. Ordered logistic regression analysis was applied to evaluate the factors affecting virus clearance (duration of virus clearance is converted into an ordered variable: ≤15d, 15-30d, >30d). All statistical analyses were performed using R (version 3.6.3). The ggplot2 package was used to plot. A twotailed p value of less than 0.05 was considered to be statistically signi cant.

Data Availability
All data generated or analyzed during this study are included in this published article.

Declarations
Author contributions CG performed the literature search, reviewed articles, completed the data analysis using the R (version 3.6.3) and wrote the manuscript. LW and KD collected clinical information of patients with COVID-19. YJ and QP reviewed the articles and provided secondary reviews during the manuscript preparation. JY designed the analysis and revised the manuscript.
Competing interests There is no con ict of interest.
Informed consent Because of the retrospective nature of the study, the Ethics Committee of the Frist People's Hospital of Yueyang determined that no patient consent was required.
Ethics approval All experimental protocols were approved by the Ethics Committee of the Frist People's Hospital of Yueyang. All methods were carried out in accordance with relevant guidelines and regulations.