key: cord-0905222-stqrf50k authors: Akbariqomi, Mostafa; Sadat Hosseini, Mahboobeh; Rashidiani, Jamal; Sedighian, Hamid; Biganeh, Hossein; Heidari, Reza; Moosazadeh Moghaddam, Mehrdad; Farnoosh, Gholamreza; Kooshki, Hamid title: Clinical characteristics and outcome of hospitalized COVID-19 patients with diabetes: A single-center, retrospective study in Iran date: 2020-09-24 journal: Diabetes Res Clin Pract DOI: 10.1016/j.diabres.2020.108467 sha: 1892a7608a0d87780e8571c6181bb1bd1222626e doc_id: 905222 cord_uid: stqrf50k Aim To describe the epidemiological and clinical characteristics along with outcomes of hospitalized Coronavirus Disease 2019 (COVID-19) patients with and without diabetes. Methods This retrospective, single-center study included 595 consecutive hospitalized patients with confirmed COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from February 26, 2020 to March 26, 2020. Demographic data, clinical, laboratory, and radiological findings were collected and compared between patients based on diabetes status. Complications and clinical outcomes were followed up until April 4, 2020. Results From among the 595 hospitalized patients with COVID-19, the median age was 55 years and 401 (67.4%) were male. The most common symptoms included fever (419 [70.4%]), dry cough (368 [61.8%]) and dyspnea (363 [61%]). A total of 148 patients (24.9%) had diabetes, and compared with patients without diabetes, these patients had more comorbidities (eg, hypertension [48.6% vs. 22.3%; P <.001]); had higher levels of white blood cell count, neutrophil count, C-reactive protein, erythrocyte sedimentation rate and blood urea nitrogen, and had a higher proportion of patchy ground-glass opacity in chest computed tomography findings (52.7% vs. 25.7%; P <.001). Significantly, patients with diabetes had more complications and needed more respiratory support than those without diabetes (P <.001). At the end of the follow-up, treatment failure and death was significantly higher in patients with diabetes compared to those without diabetes (17.8% vs. 8.7%; P = 0.003). Conclusion COVID-19 patients with diabetes are at a higher risk of complications and a higher in-hospital mortality during hospitalization. Diabetes status of COVID-19 patients and frequent monitoring of glycemia would be helpful to prevent deteriorating clinical conditions. Coronavirus disease 2019 caused by a novel coronavirus named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially reported in Wuhan, China and has rapidly become a global pandemic [1, 2] . The first patient with confirmed COVID-19 in Iran was announced from Qom province on February 19, 2020 [3] . Shortly afterwards, the infection spread rapidly throughout the country, and Iran became one of the epicenters of the COVID-19 pandemic [4] . As of July 13, 2020, a total of 257.303 laboratory-confirmed cases and over 12.000 deaths in Iran have been documented [5] . The COVID-19 infection causes an intricate situation for people with underlying diseases including cardiac disease, diabetes, hypertension and respiratory diseases, which result in rising rates of hospitalization and mortality [6, 7] . Notably, the highest number of comorbidities has been seen in infected patients admitted to the intensive care unit (ICU), suggesting that the chronic diseases are likely to be risk factors for adverse clinical outcomes [8] . In this context, the largest COVID-19 study in America found that diabetes was one of the most frequent comorbidities (33.8%) among 5700 hospitalized patients with COVID-19 [9] . Moreover, it has been shown that expression of angiotensin-converting enzyme II (ACE2) as a cell entry receptor for SARS-CoV-2 is significantly increased in diabetes patients treated with angiotensin-converting enzymes (ACE) inhibitors and angiotensin II receptor blockers (ARBs) [10] . Consequently, the ACE2 overexpression make them highly vulnerable to COVID-19 infection and may have an unfavorable prognosis. Currently, there is limited data on the characteristics and outcomes of diabetes patients hospitalized with COVID-19 in Iran. Further awareness of the baseline characteristics and risk factors for COVID-19 in different clinical settings is needed for better patient management and mitigation of disease complications. Hence, in this study it was aimed to evaluate and compare demographic and clinical characteristics, laboratory findings, treatment and outcomes of hospitalized COVID-19 patients with and without diabetes from a single medical center in Iran. This research was a retrospective study of 595 consecutive patients with confirmed COVID-19 who were admitted to Baqiyatallah Hospital from February 26, 2020 to March 26, 2020. Baqiyatallah Hospital, affiliated to Baqiyatallah University of Medical Sciences, located in Tehran province, Iran, is one of the major assigned hospitals for the treatment of COVID-19 patients by the government. All COVID-19 patients included in this study were hospitalized and were diagnosed according to the World Health Organization (WHO) interim guidance [11] . The cases infected with SARS-CoV-2 were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) assay on throat and nose swab samples. The clinical outcomes of these patients were monitored to April 4, 2020, the date of the last follow-up. This study was reviewed and approved by the ethical committee of the Baqiyatallah University of Medical Sciences, Iran (IR.BMSU.REC.1399.183). The need for written informed consent was waived by the ethics committee due to the retrospective nature of this study and the patient data anonymity. However, a verbal consent was obtained from either each patient or their next of kin before their data were included in this study. The demographic data, exposure history, clinical symptoms and signs, laboratory findings, chest X-ray or computed tomography (CT) scans, underlying comorbidities, treatment measures and outcomes data of each patient were obtained using standardized data collection forms from electronic medical records. All data collected were reviewed by an experienced team of physicians and entered into the computer database. Patients with missing data or medical recorded unknown on characteristics studied were excluded. Diabetes cases were identified based on patient's selfreport or medical records confirmed by endocrinologists. Diagnosed diabetes was defined according to the WHO diagnostic criteria of fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L). The date of disease onset was defined as the day when the first sign or symptom was appeared. Acute respiratory distress syndrome (ARDS) was diagnosed according to the Berlin definition [12] . All clinical outcomes of patients were presented after completing the hospital period at the end of the study. In this study, patients were clinically stratified into three groups of moderate, severe and critical disease according to the criteria defined as follows: Diagnostic criteria for moderate cases were: fever, respiratory symptoms and CT manifestation of pneumonia. At least one of the diagnostic criteria for severe cases was: dyspnea with a respiratory rate ≥30 breaths/min, blood oxygen saturation ≤93% at rest or partial pressure of oxygen in arterial blood (PaO2)/ fraction of inspired oxygen (FiO2) ≤300 mmHg as hypoxemia and chest imaging with progression in lesion of more than 50% within 24-48 hours. The diagnostic criteria for critical cases was: respiratory failure with mechanical ventilation need, shock and dysfunction of other organ requiring ICU care. Continuous variables were presented as mean ± standard deviation (SD) or median and interquartile range (IQR). Categorical variables were expressed as frequencies and percentages (%). The Fisher exact test or χ 2 test was applied to compare categorical variables and independent t-test or Mann-Whitney U test was applied to compare continuous variables, as appropriate. The data were analyzed using SPSS software (version 22.0; IBM). For all the statistical analyses, pvalue <0.05 was considered statistically significant. CoV-2 were included in this retrospective study. Among these patients, 148 (24.9%) and 447 (75.1%) were identified as diabetic and non-diabetic COVID-19 patients, respectively. The demographic and clinical characteristics of the studied patients according to diabetes status are shown in Table 1 The laboratory and radiographic findings at admission are shown in Table 2 P = 0.003) were more prevalent in patients with diabetes than in those without diabetes. Next, a similar analysis was performed in the absence of other comorbidities to investigate whether diabetes increases the disease severity and death per se. We found that white blood cell count Table 4 ). Comparisons of the disease severity and mortality between COVID-19 patients with diabetes and those without diabetes in the presence and absence of other comorbidities showed statistically significant differences (Fig. 2) . The present research was a retrospective study of 595 hospitalized patients with COVID-19 which were analyzed in the cases of baseline demographic, clinical characteristics, and outcomes. The rapid global expansion of COVID-19 has shown that SARS-CoV-2 has a high transmission potential in humans, especially in elderly people and those with underlying diseases. Greater proportions of hospitalized patients in this study were men (67.4%), indicating that men are at higher risk from COVID-19 infection, which in some studies the cause has been partly attributed to the high prevalence of smoking among men [13, 14] . However, in this study, current smokers accounted for a low percentage of COVID-19 patients and no significant relationship was found between smoking and COVID-19, which was consistent with a recent meta-analysis study [15] . One of the important factors in increasing the transmission of the virus is the long duration of the disease onset to hospital admission. In the present study, the time from symptom onset to hospital admission was relatively long (7 days, IQR 3.7-9 days), which indicates the need for raising awareness and public education to mitigate the spread of this infection. Recent studies have reported that diabetes is one of the most important underlying comorbidities in patients with COVID-19 and is associated with severity and mortality in these patients [16, 17] . Consistently, the data of this study showed a high prevalence of diabetes in patients with COVID-19 (24.9%) and significant statistical associations between hospitalized COVID-19 patients with diabetes and those without diabetes. According to finding, fever, dry cough, and dyspnea were most common symptoms in patients with diabetes, which were consistent with previous studies [17, 18] . Laboratory findings at admission indicated the white blood cell count increased, neutrophil count increased and lymphocyte count decreased significantly in the COVID-19 patients with diabetes compared to those without diabetes, which are consistent with earlier studies [18] [19] [20] . These findings may indicate the fact that patients with diabetes had suffered a more severe viral infection and had propensity to bacterial infections. In addition, inflammatory markers levels including Creactive protein and erythrocyte sedimentation rate were significantly higher in patient with diabetes than in patients without diabetes. Previous studies have shown the effect of Th17 cells and Treg cells on immune system imbalance and induction of inflammatory factors secretion in patients with diabetes and obesity [21, 22] . Diabetes-associated inflammatory process can result in a reduction in the immune response and more severe infection along with worse outcomes in COVID-19 patients with diabetes [23] . On the other hand, the level of blood urea nitrogen, kidney damage indicator, significantly increased in patients with diabetes compared to patients without diabetes, suggesting that kidney damage may have occurred. It is worth noting that the high level of LDH in the blood of COVID-19 patients with diabetes in the absence of other comorbidities can partly justify the more severe tissue damage compared with those without diabetes without comorbidities. Since the CT imaging results were different between patients with diabetes and without diabetes, it can be considered as an indicator to determine the severity of the COVID-19 pneumonia. Radiographic findings demonstrated that the patchy ground-glass opacity obtained from chest CT was significantly more prevalent in patients with diabetes, indicating that pneumonia was more severe in these patients. In the present study, patients with diabetes showed a more severe disease and a higher mortality rate than patients without diabetes which could be significantly related to a higher incidence of complications and coexistence with other comorbidities, especially obesity and hypertension. Many recent studies have also noticed an association between obesity and hypertension with more severe COVID-19 illness [9, 16, 24, 25] . Additionally, further analysis showed that COVID-19 patients with diabetes without these comorbidities had also more complication and death compared to those without diabetes without comorbidities. This means that other comorbidities may have only little impact on the prognosis and outcome of COVID-19 patients with diabetes. Thus, more attention should be paid to COVID-19 patients with diabetes during hospitalization. The strengths of this study were the large sample size of COVID-19 patients, comprehensive clinical records and admission of a wide range of ethnicities. In addition, as the studied hospital is one of the major designated-government hospitals for COVID-19 patients' treatment in Tehran, so, it would be a good representative of patients in the region. To the best of our knowledge, this is the first study in Iran to investigate the clinical characteristics and outcomes of hospitalized COVID-19 patients with and without diabetes. However, this study also faced some limitations. First, all included patients were only from a single center within the Tehran metropolitan area which means a nationwide multicenter study is needed. Second, the data were collected from the electronic medical records and some indicators have not been tested in all patients, so bias from missing data might exist. Third, given that most patients were still hospitalized at the end of the study and due to short-term outcome follow-up, it was difficult to assess risk factors for a poor prognosis. In conclusion, COVID-19 patients with diabetes presented a more severe infection and a worse prognosis than that of non-diabetes patients. Moreover, diabetes could be considered as a risk factor for disease progression and increase in-hospital death in patients with COVID-19. The study's findings highlighted the importance of understanding the clinical features of COVID-19 to implement effective control measures and more intensive disease management in patients with diabetes worldwide. 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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. None.