COVID-19 discharged patients in Hunan, China: correlation between early features and prognosis

Purpose To describe the correlation between the clinical, laboratory and radiological findings with hospitalization days in Coronavirus Infected Disease-19 (COVID-19) discharged patients. Method In this multicenter study, we retrospectively identified 153 discharged patients with COVID-19 pneumonia from Jan 16, 2020 to Feb 26, 2020 in Hunan province. Patients were grouped based on the hospitalization days: Group 1 (hospitalization days≦12 days) and Group 2((hospitalization days> 12days). Demographic, clinical characteristics and laboratory findings on admission and the imaging features of the first Chest CT on admission were analyzed. The differences between groups were analyzed using univariate logistic regression to find the impact factors.

COVID-19 discharged patients in Hunan, China: correlation between early features and prognosis

Introduction
Since several cases of pneumonia from unidentified pathogen have been reported in Wuhan, Hubei province, China in December 2019, an new-type coronavirus infectious pneumonia broke out rapidly, which was designated as a global healthy emergency by World Health Organization(WHO) 1 . This novel coronavirus identified from the throat swab sample by the Chinese Center for Disease Control and Prevention (CDC) was named as COVID-19 by WHO. Thus far, there has been more than 40000 confirmed cases throughout the China and involving more than 25 countries around the wold 2 .
From the recent literatures, most of the patients presented as a lower respiratory tract inflammation including fever, cough, myalgia or fatigue [3][4][5] . Manifestations are similar to other viral pneumonia such as severe acute respiratory syndrome(SARS) and middle east respiratory syndrome(MERS) 6,7 . CT imaging has been an important role in screening, primary diagnosing and monitoring patients with COVID-19, since lung imaging manifests earlier than clinical manifestations. The imaging findings reported were similar to typical viral pneumonia but with significant features 8 . Some summary articles reported were focused on the clinical and radiology findings and clinical outcomes, the outcomes were designated as severe and non-severe 9 . However, there has no article focused on the prognosis in discharged patients. The purpose of this study was to evaluate whether there is a correlation between the early clinical, laboratory and radiological findings with the different prognosis in discharged patients with COVID-19.

Materials And Methods Patients
We retrospectively identified the discharged patients with laboratory-confirmed COVID-19 from the electronic medical system and picture achieving and communication system (PACS) in two centers in Hunan after Medical Ethical Committee approval (Approved number:2020004). From the Jan 16, 2020 to Feb 26, 2020, there were totally 153 discharged patients (85 male and 68 female, with the mean age of 42.32 ± 14.03) included in this study with following criteria:1) Patients were laboratoryconfirmed COVID-19; 2) Patients were discharged without readmission; 3) Patients underwent chest CT scan and laboratory examination at the initial hospital admission. Patients with severe pneumonia during disease course were excluded. Severe pneumonia was defined as: 1) Severe respiratory distress (respiratory rate > 30 breaths/min); 2) Requirement for oxygen treatment or medical ventilation; 3) SpO2 < 90%. Asymptomatic at the beginning of admission cases and those younger than 14 years old patients were also excluded. The flowchart of patient inclusion and exclusion in this study was summarized in Fig. 1.
The diagnosis of COVID-19 based on the guideline (Trial version 5) from China National Health Commission 10 was as follows: 1) Suspected patients with detection of COVID-19 by real-time reversetranscription-polymerase chain reaction (RT-PCR); 2) Suspected patients with virus gene sequence from respiratory tract of blood sample which highly match with COVID-19. Discharge criteria based on the guideline (Trial version 5) includes: 1) Temperature returned to normal for more than 3 days and respiratory symptoms relieve significantly; 2) Chest radiologic images demonstrated significant improvement; 3) Negative nucleic acid test for two consecutive respiratory pathogens (sampling interval ≥ 1 day).
Based on the hospitalization days, we designated two groups patients in our study: group 1(hospitalization days ≤ 12 days) and group 2 (hospitalization days > 12 days).

Data collection
Demographic and clinical characteristics, laboratory findings data were reviewed from electronic medical records by two trained physicians. Demographic information included sex, age, exposure history, smoking history and underlying comorbidities. Clinical characteristics included the onset temperature and symptoms, the highest temperature and symptoms during hospital stay and the diagnosis on admission. shadowing), lesion distribution (bilateral or unilateral) and presence of bronchial abnormality (including air bronchogram sign and bronchodilation) were analyzed. A semi-quantitative CT score system was used to assess the involvement degree in each lung lobe: no involvement correspond to a score of 0, 1%-25% involvement to a sore of 1, 25%-50% score of 2, 50%-75% score of 3 and more than 75% to a score of 4 11 . For patients with mixed GGO and consolidation lesions, we defined them into two scenarios, GGO/consolidation > 1 referred to patients with GGO predominantly, and GGO/consolidation < 1 referred to consolidation predominantly, evaluated by three radiologists. After separate evaluation from each radiologist, the disagreements were discussed to made consensus.

Statistical Analysis
Continuous variables were expressed as the means and standard deviations (SD), and categorical variables were expressed as the counts and percentages in each category. We grouped patients into hospitalization days ≦ 12 days and > 12 days. Wilcoxon rank-sum tests were applied to the continuous variables, chi-square tests and Fisher's exact tests were used for categorical variables as appropriate.
P-values < 0.05 was considered as statistically significant. All the variables which have statistically significant difference between two groups were analyzed using logistic regression to find the independent influential factors. All statistical analysis was performed using SPSS(IBM).

Demographic and Clinical Characteristics
Among all 153 discharged patients with confirmed COVID-19, the average hospitalization days were 12.34 ± 4.39 (range from 4 to 25) with the median number of 12 days. The time from onset to admission, time during hospitalization and the time from onset to discharge of all patients were demonstrated in Fig. 2. We divided 153 patients into two groups based on their hospitalization days. 90(58.8%) patients who had hospital stay no more than 12 days were assigned to group 1. 63 patients (41.2%) who had longer hospitalization days (more than 12 days) were assigned to group 2.
The demographic and clinical characteristics of the patients by group are summarized in the Table 1. In the full cohort, there are 85(55.6%) male and 68(44.4%) female with the mean age of 42.3 years (SD 14.0). There was no statistically significant difference in age (p = 0.08) or gender(p = 0.43) or current smoking history (p = 0.52) between groups. A history of direct exposure to Wuhan was documented in 47.1%. Other 52.9% patients had contact with people from Wuhan, and there was no significant difference between two groups (P = 0.29). There were 6 (6.7%) patients in Group1 and 10 (15.9%) in Group2 had admitting diagnosis as non-pneumonia (p = 0.07). Some non-pneumonia patients have longer hospitalization days due to the persistent symptoms or pneumonia occurrence during admission. Their CT images were normal at first but occurred abnormalities during admission (Fig. 3). The most common symptoms at onset and during admission were fever (94, 61.4%; 92, 60.1%) and cough (62, 40.5%; 93, 60.8%) respectively. No significant difference in clinical symptoms were found between two groups. The mean temperature at onset and the highest temperature during admission were 38.43 ± 0.46 and 37.38 ± 3.06 respectively with no statistically significant difference. Laboratory and Radiologic findings Table 2 shows the laboratory and radiologic findings by groups at the initial admission. White blood cell (P = 0.04) and neutrophil (P = 0.04) count above normal were more common in Group 2 (6, 9.5%; 6, 9.5%) than in Group 1(2, 2.2%; 2, 2.2%). Patients in Group 2(11, 17.5%) had higher concentration of aspartate aminotransferase (P = 0.04) than in Group 1(6. 6.7%). Other laboratory findings didn't significantly differ between groups. Except 6(6.7%) patients in Group1 and 10(15.9%) in Group 2 without abnormal finding in Chest CT at the initial on admission, other patients had abnormal CT imaging features (  Clinical characteristic, laboratory findings, radiological findings and prognosis Five variables from clinical characteristics, laboratory findings and radiological findings that were significant difference between two groups were analyzed using univariate logistic regression. The results were summarized in Table 3  (81%) were classified as mild type which included non-pneumonia and mild pneumonia 3 . Therefore, summarizing the characteristics of mild cases would be important and helpful to improve the understanding of COVID-19.
We retrospectively observed a group of 153 discharged patients with laboratory-confirmed COVID-19 mild pneumonia in order to determine the correlation between clinical features and pneumonia prognosis. All patients had complete medical records including clinical information, laboratory and radiological data required for this study, and explicit inclusion and exclusion criteria for each patient were used to confirm the representative population. In our study, average hospitalization days of discharged patients were 12.34 ± 4.39 (range,4-25) days, and median was 12 days. In addition, very little was found in the previous literature on the question about how to divide into groups based on the hospitalization days in viral pneumonia. Thus, we used 12 days as a cut-off value to divide the discharged patients into two groups.
Fever (61.4%) and cough (40.5%) were the most common symptoms at onset in patients with COVID -19 mild pneumonia. In addition, the number of patients who had cough as the onset symptom showed a significant difference between two groups. However, the previous study did not report the correlation between symptom at onset and hospitalization days 12 . This finding might be due to the differences in small cohorts or demographic characteristics. Further study would be beneficial to reveal the possible reasons. Surprisingly, the number of non-pneumonia patients has no significant difference in two groups with different hospitalization days. That is to say, few non-pneumonia patients also have longer hospitalization days than that of mild pneumonia patients. In our cohort, the preliminary diagnoses of 10 patients who had more than 12 hospitalization days were nonpneumonia. These patients experienced multiple CT scans during hospitalization and only 2 of them were finally diagnosed as mild pneumonia due to the positive CT findings. Overall, a small part of nonpneumonia patients might have longer hospitalization days due to the persistent symptoms or pneumonia occurrence after admission.
The mean number of involved lung lobes was 2.9 and CT score was 4.3, with non-specific features such as number of lesions, morphology, distribution and bronchus involved in our cohort. These findings are similar to those of previous radiological studies of patients with COVID-19 mild pneumonia 13 . However, compared with the early characteristics of lesions which had the majority of pure ground-glass opacity 14 , the characteristics of patients in our cohort showed the majority of mixed lesions. In order to investigate the possible reasons for the discrepancies in mixed lesions, we calculated the mean admission time and the proportion of ground-glass opacity and consolidation, respectively. These results showed that the mean admission time had no difference between the two group patients, and the greater proportion of ground-glass opacity had an obvious difference between the two group patients. Further investigation using binary logistic regression also revealed that the greater proportion of ground-glass opacity was associated with the hospitalization days.
There were some limitations in our study. Firstly, as a relatively small and three-center study, it is so difficult to avoid selection bias, and characteristics of enrolled patients may not be representative.
Secondly, due to the average age of the patients in our cohort was around 40 years old, whether these results are generalizable to COVID-19 mild pneumonia patients in children or aged greater than 70 years old needs further evaluation. Finally, as lung biopsy specimens were unable to analysis in this study, the relationship between histopathological and radiological findings remains to be investigated.

Conclusions
In conclusion, this was a retrospective, multicenter, and comprehensive study focused on the impact factors in hospitalized COVID-19 mild pneumonia outcomes.