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A Consecutive Cohort with COVID-19 in Wuhan, China: Natural History, Clinical Features and Considerations

In December 2019, a novel type of coronavirus pneumonia was first reported in Wuhan, Hubei Province, China. The novel coronavirus infection, known as COVID-19, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) [1,2]. In the early days, there was nothing we could do with this disease, and because of this, high rates of person-to-person transmission and mortality were still lasting.


Introduction Data collection
Clinical data were retrospectively obtained from patients' medical, laboratory findings and chest computer tomographic (CT) scans. Clinical features included sex/age, symptoms as well as signs at admission and follow-up outcome. All patients with COVID-19 enrolled in this study were diagnosed by nucleic acid real time-polymerase chain reaction (RT-PCR) tests and treated based on the National Clinical guidelines (Edition 5) formulated by the China National Health Commission (NHC). Those with condition of one of the following clinical features was taken as a severe case: 1) Hypoxemia with reseing oxygen saturation ≤ 93%; 2) Respiratory frequency ≥ 30 times/min; 3) arterial partial oxygen pressure (PaO 2 )/oxygen absorption concentration (FiO 2 ) ≤ 300 mmHg (1 mmHg = 0.133 KPa). In addition, the critically diagnostic criteria met one of the following conditions: 1) Respiratory failure and COVID-19 infection. But clinical features and prognosis of elder patients was still unclear, with only limited literature reported. In addition, the long-term outcome of curable patients was not described in previous studies. Therefore, we mainly retrospective reviewed elder patients in severe condition from Wuhan city to provide information to give a better understanding of this disease.

Statistical analysis
The use of mean or median was determined by the type and the normality of data; mean was used for continuous variables with normal distribution (distributed evenly or not) and median was used for data of abnormal distribution or rank variables, followed by Chi-square, independent sample t-test and Mann-Whitney u test for comparison. Furthermore, the spread of data (interquartile range [IQR] for median and standard deviation for mean) was provided. We chose the variables including patients' data and laboratory investigations in the present study, which was similar to published studies. The variables for statistical analysis included age, gender, symptoms as well as signs and WBC, HGB, LY, etc.

Results
In this study, between 20 January 2020 and 24 February the 28 cases, with a mean age of 62.4 ± 14.0 years (Range 60-81 years) and 7 cases (58.3%) were males. The mean and median duration of symptoms in senior group were 7.4 ± 5.0 days and 6 days, respectively (Range, 3-20 days). The mean and median period of stay in ICU was 11.3 ± 8.2 days and 9 days (Range, 1-30 days), respectively after the date of the ICU admission. The most common symptoms of onset were cough (n = 11, 91.7%), followed by fever (n = 9, 75%) and chest distress (n = 6, 50%). We made an attempt to obtain some different clinical behavior between elder and young adult group, and found that only more young adult patients (n = 11, 84.6%) got a high fever (38.5 °C), which did not reach a statistical significance (p = 0.064) Table 3.
With regards to laboratory test findings, compared with non-elderly group, the value and positive rates of HGB and ALB in elder group were more significantly increased (p = 0.035 and p = 0.036; p = 0.016 and p = 0.019). According to assessment of infection indicators, the value of PCT was more significantly increased in senior patients than those in young adult patients (p = 0.001), but positive rate of it did not any statistical difference between these two groups (p = 0.067). Statistically significant difference was observed in value of PT and INR between these two groups (p = 0.031 and p = 0.027) Table 4.
Eleven patients (42.9%) died in ICU with uncorrectable hypoxemias; 17 patients (57.1%) got a good recovery and then received self-quarantine for a range from 14 to 28 days. Complete follow-up data, at the most recent evaluation, were available for all survivors with a long-term follow-up duration of 3 months, and the nucleic acid tests (two times) were identified to be negative in those patients. But CT scans indicated that 6 patients still had mild inflammatory exudation.
Older patients were more likely to be at a higher risk of death than their counterpart (62.4 ± 14.0 vs. 49.4 ± 3.4 years, the median age; p = 0.030). In terms of laboratory tests, the value and positive rate of ALB were more significantly decreased in death group than those in survival group (p = 0.002 and p = 0.005) and the value and positive rate of PT were more increased in death group than those in survivor group (p = 0.002 and p = 0.007). There were statistically significant differences in level of PLT (p = 0.003), PCT (p = 0.029), TBIL (p = 0.045), CK-MB (p = 0.028), LDH (p = 0.002) and INR (p = 0.006), but positive rates of these parameters did not reveal a significant difference between death and survivor group.
To be specific, patients with COVID-19 were divided into groups, as older group over 60-years-old and young group under 60-years-old. There were 12 elder cases (42.9%) among    Since human-to-human transmission was a paramount factor of an epidemic that each patient spread infection to 2.2 other individual on average [3]. Additionally, some investigations have indicated that COVID-19 had a propensity to afflict males and male patients were more likely to experience a worse prognosis compare to females [6][7][8][9].
There were some significant differences, in this study, between young adult and older patients, in clinical behaviors and laboratory tests. The fever and cough were taken as the most common symptom in many previous studies and ours [9][10][11][12]. Our study revealed that compared with young adult patients (n = 11, 84.6%), fewer older patients had a fever more than 38.5 °C, and this difference was treading toward a significance. Lian, et al. reported 15 that more older patients experienced shortness of breath and nasal obstruction. In regard to laboratory investigations, there were significantly decreased lever of ALB in older group than those in young adult group. A similar result was also reported by Lian, et al. [13] Moreover, the abnormal level of HGB, K + , PT and PCT (infection-related variable) were observed in the older group.
With regard to underlying disease, a small number of cas-

Discussion
Since December 2019, the 2019 novel coronavirus, known as severe acute respiratory syndrome corona virus 2 (SARS-Cov-2), has been spreading quickly from its origin in Wuhan city of Hubei province of China to the rest of the country [1]. In this study, we clearly described the demographics and outcome of patients with COVID-19 to provide a better understanding and control of the COVID-19 epidemic.
The median age in our series at the time of diagnosis was 58-years-old, which was similar with previous studies that reported a median age at diagnosis of 59-years-old [1,3]. In consistent with those [4,5], our study indicated that larger age was an adverse predictor of poor outcome among patients with COVID-19 as escalating rates of severe/critical and mortality with increase in age. Unfortunately, no previous study, including this current one, has performed statistical analysis to identify the strong relation between outcome and age. It was obvious; however, old adults as high risk targets were susceptible to COVID-19 pandemic. The government should take powerful measures-outdoor activities limited, adequate isolation and earlier diagnosis-to control the potential com- es had it in which there was no significant difference between mild and severe/critical group [10]. Also, our study replicated its result. On the contrary to us, one study reported that significant difference was found in underlying condition between these two groups [13].
Many previous studies described that the value of LDH and PCT were significantly increased in the severe group than those in their counterparts [6,10,12]. This result was also confirmed in our study in which the increase in PCT or LDH was a risk predictor of death due to strong relation between LDH/ PCT and cardiopulmonary as well as inflammation. In addition, elevated BNP and TBIL are more common in death patients, who had a significantly higher level than those in survivor patients. Plus, our cohort of dead cases also suggested that a poor prognosis observed a decrease in ALB. Moreover, the blood system and myocardium witnessed a devastating damage, the PT and CKMB were significantly in death group than those in survivor group [7,14]. We obtained a duplicated result.
Seventeen (57.1%) severely ill ICU patients had died at median time of 8 days (Range, 1-38 days) mainly due to acute respiratory distress syndrome, shock, acute cardiac injury and coagulation dysfunction. But we failed to identify the severity as an independent risk factor of poor prognosis compared with young adult ICU patients, those more than 60-years-old were more subjective to these severe complications. Laboratory test, such as CK, BNP, D-dimer, should be given priority.
Sheng, et al. [15] reported that viral infection was related to a higher risk of pulmonary fibrosis which might cause one of the severe complications after patients recovered from COVID-19 infections. Among the 17 patients who were negative for two-time nucleic acid tests, 6 had CT findings of pulmonary inflammation malabsorption. It was requisite and imperative to address the issue that the prevention and treatment of pulmonary fibrosis in severe/critical patients recovered from COVID-19 infection.

Conclusion
Our study clearly reported and analyzed clinical behaviors and outcome in patients with COVID-19. Old patients are a vulnerable population, and the main symptoms are fever and cough. The overwhelming part of older patients usually happened to dyspnea posterior to a short time of onset of initial symptom, which can quickly progress to critical condition. Thus, potential risks of severe of complication should be closely taken notice of, and clinical behaviors as well as laboratory tests should be fully understood. Further randomized controlled clinical trials are required to give a comprehensive understanding of the variables in older adult with COVID-19 and to identify the independent factors of death.

Credit Authorship Contribution Statement
Bin Sun and Hao Wang: Conceptualization, Writing -review & editing, Writing -original draft, Formal analysis, Methodology, Software.