New perspectives into the clinical characteristics of COVID-19 disease CURRENT STATUS: UNDER REVIEW

COVID-19 has become a global pandemic, but with very little is known about it. In this single-centered, retrospective study, we collected all 37 confirmed cases of COVID-19 diagnosed in Dazhou, Sichuan, China from January 23 to February 25, 2020and analyzed the demographic, clinical, and laboratory data. All of the cases were either imported from Wuhan and transmitted in family clusters. The average age of the patients was 45.76 ± 13.1 years. The average duration of pharyngeal swabs was 20.65 ± 6.7 days. Four (10.8%) patients were asymptomatic, 33 (89.1%) patients had increased lactic acid, 17 (45.9%) patients had increased fibrinogen C (Fib-C), and 5 (13.5%) patients had increased D-Dimers. 29 (87.9%) cases were positive for new coronavirus-specific antibodies, 4 (10.8%) cases were positive for viral nucleic acid in stool samples, 1 (2.7%) patient had positive culture of Klebsiella pneumonia. Therefore, we can predict that Lopinavir/ritonavir and abidol may not be effective in treating COVID-19.Elevated lactic acid, Fib-C, and D-dimer in patients may be predictors of disease progression. The new coronavirus-specific IgM and IgG antibodies can help to diagnose the disease. We need to pay attention to the risks posed by fecal nucleic acid positive patients.


Introduction
In December 2019, a novel Coronavirus 2019 (COVID-19) caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out first in Wuhan, China. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic. Further, as of March 15, 2020, WHO reported that more than 100 countries had been affected by the COVID-19 pandemic with about 153,517 confirmed cases and 5,735 deaths (https://www.who.int/#).. Previous studies have recognized some clinical characteristics of COVID-19 including the median incubation period estimated to be 4 days (interquartile range, 2 to 7) 1 and the most common symptoms are fever, cough, shortness of breath, muscle pain, headache, chest pain, nausea, vomiting, and diarrhea in some patients. Chest CT mainly manifests as large patches in both lungs and ground-glass opacity. The disease rapidly progresses to acute respiratory distress syndrome (ARDS) and multiple organ failure which results in death. 2 However, during the treatment process, we discovered some new challenges that need to be addressed.

Results
The study included 37 patients diagnosed with COVID-19, out of which 13 (35.1%) patients had a clear history of exposure to Wuhan, and the 24 patients were imported second-generation cases. The average age of the patients was 45.76±13.1 years and the maximum age was 82 years. The gender representation of the patients was 56.8% male and 43.2% female. The average duration of pharyngeal swabs was 20.65±6.7 days. Four (10.8%) patients were asymptomatic who were all females and the duration of nucleic acid positive in asymptomatic infections was 11-35 days (table 1) (Table 2).
During hospitalization, screening of all the patients for influenza A virus (H1N1, H3N2), influenza B virus, respiratory syncytial virus, and adenovirus antigen/antibody was performed. All the patients tested negative for all the above viruses but showed lung consolidation. Patients with significantly elevated infection parameters had a sputum culture. Only 1 (2.7%) of the patients had developed Klebsiella pneumonia with no history of concomitant disease. However, the patient improved after antibiotic treatment (Table 3).
Among all the COVID-19 confirmed patients, 35 (94.6%) patients were treated with alpha-interferon nebulization combined with abidol or lopinavir/ritonavir antiviral therapy. A total of 12 (32.4%) patients were treated with Abidol and 23 (62.2%) patients with lopinavir/ritonavir. Elevated infection parameters (leukocyte, C-reactive protein, or calcitonin source) or positive sputum culture were reported in 7 (18.9%) patients. For patients with lower lymphocytes and longer nucleic acid positive duration, human immunoglobulin 10g/d was administered for 3-5 days. Only a few patients experienced a transient increase in transaminase and poor appetite during antiviral treatment. Since COVID-19 is a new infectious disease with the rapid transmission, psychological intervention is also necessary for some patients who may develop anxiety and depression. A total of 4 (10.8%) patients received the psychological intervention (table 4).
By comparing the number of cloudy days of nucleic acid in patients treated with lopinavir/ritonavir and abidol, it was found that P>0.05, neither of which was statistically significant (table 5).
Typical imaging features from one of the patients with diabetes and the new coronavirus pneumonia were collected (Figure 1). At the onset, the ground-glass opacity of both lungs progressed rapidly and gradually changed. This suggested an increase in exudation in both lungs, reaching a peak of exudation at about 15 days. The entire course of this patient's covid-19 was 2 months.

Discussion
Coronavirus is an enveloped positive-sense RNA virus, belonging to the Coronaviridae and segment- The increase in lactic acid is often caused by anaerobic fermentation. We found that 33 (89.1%) patients had increased lactic acid which was mainly accumulated in the lungs. We speculated that in the early stages of the disease, patients experience different levels of hypoxia due to lung infiltration or fever. Therefore, there is a need to correct the hypoxia in COVID-19 patients in a good time. Peng YD 18 and others also found that lactic acid accumulation and thrombosis can exacerbate the risk of death in COVID-19 patients. Therefore, we advocate for close monitoring of the patients' lactic acid, internal environmental conditions, and hypoxia to prevent the disease from aggravating to multiple organ failure and even death.
Generally, IgM can be produced 3-5 days after exposure to pathogenic microorganisms. IgG usually appears after IgM and can persist for many years after the infection. In this study, 33 patients Besides, there is also a need to pay attention to the problem of nucleic acid positive in stool and take appropriate preventive measures as early as possible. Finally, the use of lopinavir/ritonavir and abidol in COVID-19 patients may not be effective hence more effective treatments should be investigated.
Methods responsible for coordinating the work of various departments. CL,FZ, PW, FZ and XZ revised the final manuscript. HW, SD and DL assisted in data analysis. JL and CX assistd in data collection. QG assisted in consulting the literature. FZ is responsible for the source of funds.