Clinical course and outcome of novel coronavirus COVID-19 infection in 107 patients discharged from the Wuhan hospital

Background In December 2019, Coronavirus Disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical progress and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. Methods Retrospective case series of COVID-19 patients from Hospital of University in and Hospital, Hubei up to February 10, 2020. Epidemiological, demographic and clinical data were collected. Clinical progress of survivors and non-survivors were compared. Risk factors for death were analyzed. Results A total of 107 discharged patients with COVID-19 were enrolled. The clinical progression of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia and radiological multilobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury or adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome , refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia and death. Older age and male sex were independent risk factors for poor outcome of the illness. Conclusions A period of 7–13 days after illness onset is the critical stage in COVID-19 progression. Age and male gender were independent risk factors for death of COVID-19.

the whole-genome level to a bat coronavirus, and suggesting that bats are the primary source. 4,5 Epidemiologic investigations of initial cases showed COVID-19 was linked with exposure to Wuhan seafood market which also sold live rabbits, snakes, and other animals. 6 Subsequently, human-tohuman transmission among close contacts has been the primary mechanism of transmission. 7 The disease has spread rapidly in China and more than 60,000 cases of COVID-19 have been reported.
Sporadic cases have also been confirmed in other countries, mainly among travelers from Wuhan and their contacts. 8,9 The incubation period of COVID-19 is thought to be up to14 days following exposure. 6,7,10 The principal presenting features of COVID-19 are fever, cough, dyspnea and bilateral infiltrates on chest imaging. 11,12 Approximately 20 percent of patients progress to multi-organ dysfunction (including respiratory failure, septic shock, acute cardiac injury or acute renal failure. 11−13 However, a complete picture of the clinical progression of COVID-19 has not been reported. Except for infection control and supportive therapy, there is no specific therapy of COVID-19. Multiple organ support therapy is the corner stone in the treatment of critically ill patients with COVID-19. 13 Early recognition of risk factors for death would be useful to identify those potentially needing critical care at an early stage. Accordingly, a dynamic study was conducted to track clinical progression along the entire disease course. Risk factor analysis was performed to reveal important clinical features associated with the poor outcome.

Methods Study Design And Participants
This case series was approved by the institutional ethics board of Zhongnan Hospital of Wuhan University and Xishui People's Hospital (No. 2020020). All the discharged (alive and dead) patients with confirmed COVID-19 from Zhongnan Hospital of Wuhan University and Xishui People's Hospital up to February 10, 2020, were enrolled. Oral consent was obtained from patients or patients' relatives. Zhongnan Hospital, located in Wuhan, Hubei Province, the endemic areas of COVID-19, is one of the major tertiary teaching hospitals and responsible for the treatments for COVID-19 assigned by the government. Xishui People's Hospital located in Huanggang city, another early endemic centre of COVID-19 in Hubei province. All patients with COVID-19 enrolled in this study were diagnosed according to World Health Organization interim guidance. 14 The methodology of RT-PCR used has been previously reported. 13

Data Collection
The medical records of patients were analyzed by the research team of the Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University. Epidemiological, clinical, laboratory, and radiological characteristics and treatment and outcomes data were obtained with data collection forms from electronic medical records and reviewed by a trained team of physicians. Information recorded included demographic data, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, chest computed tomographic (CT) scans, treatment measures (ie, antiviral therapy, corticosteroid therapy, respiratory support, kidney replacement therapy) and outcome. The date of disease onset was defined as the day when the first symptom was noticed.
acute respiratory distress syndrome (ARDS) was defined according to the Berlin definition. 15 Acute kidney injury (AKI) was identified according to the Kidney Disease: Improving Global Outcomes definition. 16 Cardiac injury was defined if the serum levels of cardiac biomarkers (eg, troponin I) were above the 99th percentile of upper reference limit or if new abnormalities were shown in echocardiography. Times from onset of disease to hospital admission, dyspnea, ARDS, ICU admission and hospital discharge were recorded.

Statistical analysis
Categorical variables were described using frequencies and percentage, while continuous variables were described using mean, median, and interquartile range (IQR) values. Means for continuous variables were compared using independent group Student's t tests when the data were normally distributed and the Mann-Whitney test when they were not. Proportions for categorical variables were compared using the χ2 test, although Fisher's exact test was used when the data were sparse.
Univariate analyses were performed to evaluate the risk factors associated with death. Multiple logistic regression analysis was used to identify independent predictors of mortality. All the tests were two-tailed and p-value less than 0.05 was considered statistically significant. All analyses were processed by SPSS for Windows version 17.0 (SPSS, Chicago, IL, USA).

Basic Characteristics
Basic characteristics of the 107 patients (95 from Zhongnan and 12 from Xi-Shui) are shown in      (Table 3). On multivariable analysis, older age and male gender remained significant independent risk factors for death (Table 4).

Discussion
Studies on COVID-19 have generally been limited to the description of the initial clinical, haematological, radiological and microbiological findings. Herein, we firstly described the clinical progression of virologically confirmed COVID-19. This study enrolled 107 discharged patients with COVID-19 which included 88 survivors and 19 non-survivors. We also analyzed the prognosis factors and found that age and male gender were the independent risk factor for mortality.
This study showed the clinical progression of COVID-19 presented as a tri-phasic pattern. In week 3, the organ functions improved in survivors, but continued to deteriorate the non-survivors.
The lymphocyte counts dropped further and immune dysfunction became obvious in the nonsurvivors. These patients developed severe ARDS necessitating ventilation and even ECMO support, septic shock supported by vasopressors, and an-end stage renal failure requiring continuous renal replacement therapy. Coagulation dysfunction and thrombocytopenia also developed. Death was inevitable due to multiorgan failure.
Notably, most non-survivors in our study were old male. Multivariate analysis showed older age and male gender were independent risk factors for death. A recent study examining single-cell RNA expression profiling of angiotensin converting enzyme 2 (ACE2), the cellular receptor of SARS-CoV-2, showed that Asian males had an extremely large number of ACE2-expressing cells in the lung. 17,18 A finding that might underlie the higher risk of death in this population.
After the incubation period, the frequent manifestations of COVID-19 were fever, cough, dyspnea, and bilateral infiltrates on chest imaging. 11−13 Evidence has shown that SARS-CoV-2 was found in the loose stool of a patient and potential transmission through the faecal-oral route should be considered. 19,20 Consistent with the finding, some patients showed digestive symptoms (e.g. abdominal pain, diarrhea, nausea, and vomiting) at the illness onset. Multi-lobar involvement on initial chest CT was shown in most of our patients, consistent with a primary pulmonary method of acquisition.
Until now, no fully proven and specific antiviral treatment for the SARS-CoV-2 infection exists. Organ support therapy is the corner stone in the treatment of critically ill patients with SARS-CoV-2 infection.
Remdesivir, a novel nucleotide analog antiviral drug has been used in the first case with COVID-19 in the US and a clinical trial of remdesivir in SARS-CoV-2 infection is in progress. 21

Consent for publication
No individual participant data is reported that would require consent to publish from the participant (or legal parent or guardian for children).