Analysis of clinical characteristics of SARS-CoV-2 infected cases: a retrospective study of medical records

In order to identify the clinical and clinical and laboratory data, we analyzed the medical records of 80 suspected cases who admitted in the national designated hospital due to the relevant clinical manifestations of SARS-CoV-2 infection from January 22 to February 13, 2020. 62 (77.5%) confirmed cases and 18 (22.5%) negative cases were confirmed by SARS-CoV-2 nucleic acid test. Epidemiological investigation and statistical analysis were carried out on the clinical and laboratory data of all suspected cases of COVID-19, the specific indicators were found, and the clinical characteristics of COVID-19 were described. Compared with the patients with negative nucleic acid test, the patients with positive nucleic acid test showed shorter time of onset of symptoms, higher plasma CO 2 level, lower eosinophil ratio, lower platelet count and hematocrit, lower serum sodium level, higher serum creatinine, higher blood urea and plasma albumin levels (all P <0.05). Our results might provide some suggestions in diagnosis, clinical treatment and prevention for COVID-19.

Classifying the clinical characteristics of COVID-19 patients is of great significance for the rapid diagnosis of SARS-CoV-2 as well as clinical treatment and care. Herein, we analyzed the clinical characteristics of 62 SARS-CoV-2 nucleic acid positive cases and 18 negative cases. Based on the contact history, clinical symptoms, blood and biochemical test results, chest computed tomography (CT) results, and combined with the gold standard for clinical detection of virus RNA to diagnose suspected cases, we diagnosed 80 suspected cases admitted to hospital, reviewed the physiotherapy records of all cases, and found that compared with SARS-CoV-2 nucleic acid test negative cases, positive cases had shorter onset time of symptoms and higher plasma CO 2 levels. And the proportion of eosinophils decreased, platelet count and hematocrit decreased, the level of serum sodium was lower, while the levels of serum creatinine, blood urea and plasma albumin were higher in positive cases, suggesting that viral infection could damage bone marrow hematopoiesis, liver and kidney function. The characteristic changes of these indexes related to blood coagulation, hematopoiesis, liver and kidney function provide a new perspective for the diagnosis, clinical treatment and nursing of COVID-19.
Compared with other patients, patients who were diagnosed with COVID-19 by viral nucleic acid assay had lower median duration from onset of symptom to hospital admission (8 days, IRQ, 5-10 vs 10 days, IRQ, 7-15; P=0.014).
Results of the multivariable logistic regression model for determining risk factors for positive outcome of the viral nucleic acid assay are displayed (Table 5). Age, hypersensitive C-reactive protein and albumin were positively associated with positive result of the viral nucleic acid assay, while time from symptom occurrence to admission was negatively related to that.

Discussion
Increasing evidence suggested that COVID-19 is highly contagious [7] . It has been reported that its basic reproduction number (RO) is 3.77, which is estimated to spread to 3.77 other people per patient on average [7] , and the incubation period of the disease can be as long as two weeks [2] . However, our report indicates the onset of symptom to hospital admission in SARS-CoV-2 nucleic acid test positive cases is less than that in SARS-CoV-2 nucleic acid test negative cases. Which suggesting that although there is a long incubation period after contact with COVID-19 patients, nucleic acid test positive patients will appear typical SARS-CoV-2 symptoms more quickly compared with negative cases after admission to hospital with suspected symptoms such as fever and cough. That indicates the onset of COVID-19 is sudden, and patients may show atypical or SARS symptoms in the early stage. The strong infectivity, long incubation period, rapid onset and the diversity of clinical symptoms of COVID-19, increase the difficulty of diagnosis, treatment, nursing and clinical research for it. As a new severe infectious disease, there is no particularly effective prevention and treatment for it. Hence it is essential to classify the specific clinical features of COVID-19, which will play a certain role in the prevention and treatment of COVID-19.
It has been reported that SARS-CoV-2 has pulmonary aggressiveness [8] . Our report shows that the blood CO 2 level of nucleic acid test positive cases is significantly increased, which is a sign of a significant decrease in the ability of the lungs to exchange gas, which confirms the pulmonary aggressiveness of SARS-CoV-2. The scary thing is that SARS-CoV-2 infection can also cause multiple organ damage to the heart, liver, kidney and bone marrow.
We found that the level of high sensitivity C-reactive protein was significantly increased in patients with positive SARS-CoV-2 nucleic acid test. The function of high-sensitivity C-reactive protein is similar to that of traditional C-reactive protein, and its elevated level is one of the manifestations of inflammation [9] .And it has been reported that elevated high-sensitivity C-reactive protein may also be one of the early markers of myocardial injury [10,11] ,which indicates that SARS-CoV-2 infection may cause myocardial injury in patients, although further pathological studies are needed to prove this idea. In addition, we found that compared with the patients with negative nucleic acid test, the patients with positive nucleic acid test had lower platelet count and hematocrit, shorter prothrombin time and longer activated partial thromboplastin time, which indicated that the coagulation function of patients with positive nucleic acid test was damaged by virus infection. Good blood coagulation depends on good hematopoiesis and liver function, so we speculate that hematopoiesis and liver function are damaged by SARS-CoV-2 infection, which is in line with similar previous research conclusions [10,11] ; We found that the level of serum sodium, which is closely related and interdepende to water [12] , in patients with positive nucleic acid test was lower than that in patients with negative nucleic acid test, which may be due to high fever and sweating caused by viral infection, acute loss of water or loss of digestive juice caused by vomiting and diarrhea. Studies have shown that fever (91.7%), cough (75.0%), fatigue (75.0%) and gastrointestinal symptoms (39.6%) after SARS-CoV-2 infection are the most common clinical manifestations [13] . Sweating and loss of digestive juices both cause sodium to be excreted with the liquid. However, patients with negative nucleic acid test also have high fever, sweating and loss of digestive juice. whether the symptoms of hyponatremia in patients with positive nucleic acid test are the consequence of renal dysfunction caused by viral infection is a conjecture worth considering. The evidence to support this conjecture also includes that the blood creatinine, uric acid and urea in patients with positive nucleic acid test are significantly higher than those in patients with negative nucleic acid test (see Table2 for details). The level of plasma albumin in patients with positive nucleic acid test is higher than that in patients with negative nucleic acid test, which is another situation that we should pay attention to. Plasma albumin is the most abundant protein in plasma, and it is also a kind of nutrient. in special cases, its decomposition can produce amino acids that participate in the synthesis of tissue proteins [14] , or oxidative decomposition to produce energy [15] . In addition, plasma albumin can also play a role in stabilizing globulin, which is of great significance in antiviral effect [16] . High fever and sweating after virus infection, acute dehydration caused by diarrhea and vomiting will lead to an increase in the concentration of serum albumin. At the same time, in order to make up for the decrease of plasma osmotic pressure caused by the decrease of blood sodium, plasma albumin will also increase adaptively. The increase of albumin will protect the body in the early stage of SARS-CoV-2 infection, but some clinicians have found that the level of plasma albumin will continue to decrease with the progress of infection, which may be due to the difficulty of eating caused by the continuous progress of COVID-19, or it may be the liver function damage caused by SARS-CoV-2 infection that just discussed leads to the decrease of albumin.
In the process of analysis, we also found that the age of patients with positive nucleic acid test was higher than that of patients with negative nucleic acid test, and it was statistically significant. This shows that the older group is more likely to be infected with SARS-CoV-2, which is related to their declining immune function and physical fitness; comparing the number of eosinophils in the sample, it can be found that the number of patients with positive nucleic acid test is lower, which may be the result of treatment with corticosteroids during treatment, or it may be caused by excessive and negative cases, we find that compared with nucleic acid test negative cases. The patients with positive nucleic acid test had higher blood CO2 level, lower eosinophil ratio, lower platelet count and crit, lower serum sodium level, and higher serum creatinine, blood urea and plasma albumin levels, suggesting that SARS-CoV-2 infection will cause damage to many organs, especially liver and kidney function and bone marrow hematopoietic function. This is our description of the clinical characteristics of SARS-CoV-2 infection. During clinical treatment, we must pay close attention to patients' blood CO2, blood urea, serum creatinine levels, blood coagulation function, timely detection of patients' liver and kidney function, and timely correction of disorders, which will play a positive role in improving the prognosis of patients.

Study design and participants
From January 22 to February 13, 2020, we enrolled consecutive patients with acute respiratory tract symptoms admitted to a hospital (Ezhou, Hubei, China). All enrolled patients were tested for nucleic acid of SARS-CoV-2 during the hospital stay. The diagnosis of SARS-CoV-2-infected pneumonia is made according to World Health Organization interim guidance. Written informed consent were acquired from the patients involved. This case series is approved by the Ethics Committee of Medical Department of Wuhan University.

Data collection
For this retrospective study, patients' clinical records were obtained and organized into tabular data.
The information collected involved demographic data, exposure history, medical comorbidities, signs, symptoms, laboratory findings, treatment measures (including antiviral therapy, antibacterial therapy, corticosteroid therapy, oxygen therapy and other supportive treatments) and outcomes of the enrolled patients. For ensuring data accuracy, the data forms were independently reviewed by two investigators of our research team.

Nucleic acid testing for SARS-CoV-2
Patients' throat swab samples were obtained and then placed into a collection tube with viral transport media. Total RNA was extracted from the samples within 2h through use of respiratory sample RNA isolation kit, followed by reverse transcription. Subsequently, real-time reverse transcription polymerase chain reaction (RT-PCR) assay was performed to quantified two target Diagnostic criteria of COVID-19 were that a positive result is defined as a cycle threshold value (Ctvalue) lower than 37, and a negative result is defined as Ct-value equal to or higher than 40. A medium Ct-value ranging between 37 and less than 40 required retesting for further confirmation. Ethics approval and consent to participate: This case series is approved by the Ethics Committee of Medical Department of Wuhan University.

2.
Consent for publication: All authors agree to publish.

3.
Availability of data and material: Availability of data and information.

4.
Competing interests: None of the authors have any competing interests.

Authors' contributions:
Han Zhang did a formal analysis and wrote the original draft.
Lian Lu did a investigation and found resources.
Wei Hu found a methodology and supervised the whole process.
Jian Zhang conducted data planning and performed data analysis using software.
Wei Zhu conceptualized and visualized the subject.
Qi-Qiang He conceptualized the topic and looked for a verification method.
Corresponding Author Cheng-Cao Sun is also responsible for data planning, form analysis, and supervision.
Corresponding Author De-Jia Li was responsible for project management and review and editing of the original draft.

7.
Acute    Table 5. Multivariable logistic regression model for determining risk factors for positive result of the viral nucleic acid assay.