Since the outbreak of new coronavirus pneumonia COVID-19, more than 800,000 people have been infected worldwide, far larger than the SARS in 2003, and it has evolved into a global pandemic(1). Such diseases are mainly transmitted through respiratory droplets and close contact, and the clinical features of different individuals vary greatly (2, 3) . At the same time, there are data showing that about one-quarter of patients with new coronary pneumonia in China currently have comorbidities. The presence of comorbidities can easily lead to a poor clinical prognosis, contributing to rapid progression of the disease to acute respiratory distress syndrome, respiratory failure and even death. Compared with patients without . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) comorbidities, as long as a patient has a comorbidity, the risk of poor prognosis will increase by about 79% (4). Previous studies have shown that among patients with H7N9 infection, any comorbidities may lead to a 3.4-fold increased risk developing into acute respiratory distress syndrome (5). Therefore, in the case of pneumonia patients with other diseases, the treatment of comorbidities is also very important.
This article summarizes the characteristics of 132 cases of patients diagnosed with COVID-19 combined with other comorbidities, in order to provide some ideas for the prevention and treatment of patients with comorbidities.
459 consecutive cases were from Hubei Third People's Hospital from January 19, 2020 to March 7, 2020, of which 132 patients with comorbidities were enrolled for this study (accounting for 28.8%).There is a retrospective study of 132 patients, all enrolled patients were diagnosed with COVID-19 pneumonia according to WHO interim guidance (6). 132 patients were divided into two groups: the mild group and the critical group. This study was approved by the Ethics Committee of Hubei Third People's Hospital and the hospital granted a waiver of informed consent from study participants.
To identify COVID-19 infection, throat swab samples were obtained from all patients at admission and tested using real-time reverse transcriptase-polymerase chain reaction assays according to the same protocol described previously (7). All patient's data was stored in a locked, password protected computer, and the majority of the clinical data used in this study was collected from the first day of hospital admission indicated otherwise. Common observation biomarkers including blood routine, lipid profiles, liver damage indices, renal dysfunction indices, coagulation function indices, and inflammatory biomarkers and other biomarkers were measured . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) by standard laboratory techniques.
Statistical analyses were performed using SPSS 22.0 for Windows (SPSS, Chicago, Illinois). Continuous variables were expressed as mean (standard deviation, SD) in the case of normal distribution, and differences were determined by Student t test. Data were expressed as a median (25th and 75th percentiles: P25, P75) in the case of skewed distribution and were compared using the Mann-Whitney U test .Categorical variables were presented as a number and percentage and were compared using the χ 2 test. To explore the risk factors associated with in-hospital death, multivariate logistic regression models were used .Considering the total number of deaths (n=13) in our study and to avoid overfitting in the model, the variables that were considered significant in previous univariate analysis were chosen for multivariate analysis. The results of logistic regression analysis were presented as an odds ratio (OR) and 95% confidence interval (CI). The A 2-tailed P < .05 was considered significant.
132 patients diagnosed with COVID-19 pneumonia with comorbidities were enrolled, accounting for 28.8% of the patients diagnosed with COVID-19 pneumonia (n=459) in our hospital during the same period, including 109 cases in the mild group and 23 cases in critical group. The age of enrolled patients with comorbidities was 63.4 years (56, 71). 76 were males (57.6%) and 56 were females (42.4%) respectively.
The most common symptom was fever(65.9%),the same as cough or sputum(65.9%).Followed by the fever was fatigue with anorexia(34.8%). and both 19.7% of patients had dyspnea and palpitations with chest tightness. The average time of hospitalization was 16.9 (9, 22) days, and there was no significant difference between the mild group and the critical group (P = 0.209). Hypertension was the most . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 12, 2020. . common comorbidity (68.2%), followed by diabetes (34.1%), coronary heart disease (23.5%), and hyperlipidemia (14.4%). Patients with stroke and chronic kidney disease only were 5.3% and 4.5% respectively .The highest proportion of drug used for treatment during hospitalization was antibiotics (77.3%), followed by Arbidol hydrochloride (60.1%) and 40mg methylprednisolone twice a day(49.2%).The percentage of using Oseltamivir and Ribavirin was 34.1% and 27.3%.The all-cause mortality rate was 9.8%, of which 7 patients died of respiratory failure, 5 patients died of heart failure, and 1patient died of chronic renal failure. There was significant statistical difference of mortality rates between the mild group (5.5%) and the critical group (30.4%) (P <0.05). 
There was significant statistical difference of mortality rates between the mild group (5.5%) and the critical group (30.4%).Male patients accounted for 69.2% of deaths, and most of them were over 65 years old (69.2%). Among them, the highest proportion of combined with hypertension was 76.9%, followed by coronary heart disease (53.8%). Compared with the survivor group, the proportion of death cases with coronary heart disease was significantly higher in the non-survivor group, with a statistically significant difference (P <0.05), the same as the neutrophils in the dead group was significantly increased (P <0.05). At the same time, we observed that . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 12, 2020. . compared with survivor group, the patients in the non-survivor group demonstrated increased lymphocyte ratio, and NLR, while lower lymphocytes, eosinophils, monocyte ratio, and monocytes. AST and BUN of the patients in the non-survivor group were similarly significantly higher than those in the survivor group. Then we compared the differences of inflammatory factors between the two groups. Compared with the survivor group, the levels of PCT, CRP, SAA and IL-6 in the non-survivor group were significantly increased (P <0.01). In the coagulation indices, the patients in the non-survivor group showed increased D-dimer and FDP than those in the survivor group (P <0.05). 
With the rapid COVID-19 spread worldwide, the prevention and control of pandemics should come first. Based on the current study, a study of 1,590 patients with COVID-19 pneumonia in China showed that 25.1% of patients had two or more comorbidities , Which means that about a quarter of the infected population suffers from comorbidities(4). The rate in our study was a slightly higher (28.8%) than previous studies. The risk of progression to from the mild type to critical type and mortality rate of COVID-19 pneumonia with comorbidities was significantly higher.
. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 12, 2020. . Furthermore, we observed that the proportion of patients with hypertension is the highest (8, 9), and the ratio of patients with diabetes or coronary heart disease is similar. Although there is no statistical difference whether with comorbidities or not between the two groups, Bivariate cox regression logistic regression analysis showed that past medical history of coronary heart disease is one of the risk factors associated with death.
In addition, we observed that the usage rate of low-dose methyl prednisolones, antibiotics, gamma globulin, and albumin in the critical group was significantly higher than that in the mild group. At the same time, we found some interesting characteristics in laboratory indices between the two groups at admission. COVID-19 pneumonia patients with comorbidities have higher percentages of neutrophils, neutrophil ratio, inflammatory biomarkers, and lower percentages of lymphocytes, lymphocyte ratio, and albumin. This also suggests that patients with comorbidities have a high prevalence of progression to severe disease, and are more likely to induce bacterial infections and cause inflammatory storm. Therefore, for such patients, targeted diagnosis and management and early treatment of basic diseases are of great significance for reducing patient mortality and effectively preventing and controlling the epidemic (10, 11). The autopsy on patients died of COVID-19 Pneumonia demonstrated that the structure of myocardial cells in patients was intact, and only a small amount of monocyte infiltration in the intercellular substance was observed(12, 13).Our study also did not observe a significant increase in the biomarkers that directly cause myocardial damage in critical group. The elevated level of NT-pro BNP in critical group may be related to patients with cardiovascular disease.
Subsequently, we divided patients with comorbidities into the survivor group and the non-survivor group, and compared the general data and laboratory biomarkers between the two groups. Similarly, the proportion of died patients with coronary heart disease was significantly higher than the survivor group , And No significant differences were observed in age and gender between the two groups. Compared with the survivor group, the neutrophil ratio in died patients was significantly increased when they were admitted to the hospital, while the proportion and count of . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.07.20092882 doi: medRxiv preprint lymphocytes and monocytes were significantly decreased, which indicates that the patient's immune system is damaged to a certain extent. Some researchers analyzed the peripheral blood of patients by flow cytometry and found that the number of CD4 + and CD8 + T cells in the blood was significantly reduced, but the cell state was over-activated, showing an increase in the number of Th17 and high CD8 + T cell cytotoxicity (8, 14, 15 ). It is proposed that lymphopenia is a common feature of COVID-19 patients, which may be related to disease severity and mortality (2, 7, 12) .
We conducted a multivariate cox regression analysis on the indices with statistical differences in the univariate analysis. The results also showed that past medical coronary heart disease history and decreased lymphocytes are independent risk factors for death of COVID-19 pneumonia patients with comorbidities.
In order to explore the patients' inflammatory state, the levels of inflammatory biomarkers were measured. PCT, CRP, SSA, and IL-6 in the patients in the non-survivor group were also significantly increased. Once the activation of inflammatory pathways in patients activated, it was very likely to quickly cause organ failure and eventually threaten life (16) . Immunological research (8, 17) showed that IL-6 is an important pathway to induce inflammatory storms, and patients with COVID-19 virus infection are different from the previous SARS virus, some patients may have early onset and are not severe or even mild symptoms. However, the activation of the later inflammatory storm may accelerate the patient into a state of multiple organ failure, especially in patients with comorbidities. Furthermore, the results of this study showed that the AST, D-dimer, and fibrin degradation products were significantly higher in the non-survivor group than in the survivor group.
Previous research have shown that the main causes of liver injury of new coronary pneumonia include immune injury, drug factors, systemic inflammation and ischemia-hypoxia-reperfusion injury (18, 19) . On the one hand, many patients have already taken one or more antiviral drugs when they were admitted to the hospital. On the other hand, under the condition of shock and hypoxia, there were oxygen deprivation, lipid aggregation, and glycogen depletion in the liver cells, which inhibited cell survival signals, causing liver cell damage and death. In addition, an . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 12, 2020. 13. yaqian m, Lin W, Wen J, Chen G. Clinical and pathological characteristics of . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
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The copyright holder for this preprint this version posted May 12, 2020. Renal failure 1 1 0 CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 12, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 12, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 12, 2020. . https://doi.org/10.1101/2020.05.07.20092882 doi: medRxiv preprint