key: cord-0843378-wcnmhe0p
authors: Borzouei, Shiva; Mohammadian-khoshnood, Maryam; Omidi, Tahereh; Bashirian, Saeid; Bahreini, Fatemeh; Heidarimoghadam, Rezvan; Khazaei, Salman
title: Predictors of COVID-19 related death in diabetes patients: A case-control study in Iran
date: 2021-05-21
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2021.05.022
sha: 5708c9351a88aca679c0287ce8b3d27f40908f73
doc_id: 843378
cord_uid: wcnmhe0p

BACKGROUND: Identifying the predictors of COVID-19 related death in diabetes patients can assist physicians for detecting risk factors related to the worse outcome in these patients. In this study we investigated the predictors of the death in patients with diabetes compared with non-diabetic COVID-19 patients. METHODS: In the present case-control study, the case group were diabetic patients with COVID-19 and the control group included Non-diabetic COVID-19 patients. The data source regarding the demographic characteristics, clinical symptoms, laboratory, and radiological findings on admission as well as the complications, treatment, and outcomes during hospitalization were gathered from their medical record through two trained nurses. Adjusted and unadjusted odds ratios (OR) estimate were calculated using the simple and multiple logistic regression through backward model. RESULTS: The mean (SD) age of the case group was higher than that of the control group; [65.24 (12.40) years vs. 59.35 (17.34) years, respectively (P < 0.001)]. Results of the adjusted logistic regression model showed that, advanced age (+60 year) (OR = 5.13, P = 0.006), addiction (OR = 5.26, P = 0.033), high level of Blood urea nitrogen (OR = 5.85, P < 0.001), and high level of Alkaline Phosphatase (OR = 3.38, P = 0.012) in diabetic patients were significantly associated with increase the odds of death in COVID-19 patients. CONCLUSION: We found that in COVID-19 patients with diabetes; advanced age, addiction, high level of BUN and Alp and in non-diabetic COVID-19 patients advanced age, dyspnea, high level of BUN and SGOT were associated with increase risk of death in these patients.

Diabetes is one of the most common non-communicable diseases worldwide and there is evidence of its substantial increasing trend in recent years (1) . Several studies have revealed a higher vulnerability to some infectious diseases in diabetic people (2, 3) . Decreased T cellmediated immune response and impaired neutrophil functionin diabetics can explain this higher susceptibility (2) .

Alongside severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), coronavirus disease 2019 )COVID-19( is another common type of coronavirus that infect humans (4) . The role of diabetes in increasing of mortality and morbidity in patients with SARS have been shown previously (5) . Also, noticeable proportion of identified patients are diabetic. In such a way that, the rate of diabetes and COVID-19 comorbidity is range from 20-50% in different global regions (6) . Published studies showed that some underlying diseases such as hypertension and diabetes mellitus are important risk factors for the fatality of COVID-19 patients (7) (8) (9) .

Although, studies have been designed to identify death-related factors in COVID-19 patients.

However, most of them are conducted on the total COVID-19 cases, regardless of having an underlying disease or not, or the investigated variables were rare. Identifying the predictors of death in diabetic COVID-19 patients helps in better management of them, and assist physicians for detecting risk factors which contributes to the severity and mortality of COVID-19 in these patients. This study was conducted in order to identify the predictors of the worse outcome in patients with diabetes in whom COVID-19 was confirmed compared with non-diabetic COVID-19 patients.

In the present case-control study, we identified all patients admitted to Sina Hospital and Beheshti Hospital in Hamadan province, the west of Iran, which was assigned to admit COVID-19 adult patients. Patients recruited from January, 2020 to January, 2021.

The Ethics Committee of the Hamadan University of Medical Sciences approved this study (IR.UMSHA.REC.1399.841). In this study, patients with positive real time reverse transcriptase polymerase chain reaction (RT-PCR) on samples from upper respiratory nasopharyngeal swabs were enrolled to the study.

The case group included diabetic patients with COVID-19 and the control group included Nondiabetic COVID-19 patients. Accordingly, all 420 diagnosed diabetic patients with confirmed COVID-19 in the above mentioned time period were included and considered as case group and for increase the statistical power of the study, compared them with 1260 non-diabetic patients with COVID-19, as controls group. Controls were selected at the same time and from the same hospital in order to overcome some potential confounders such as quality of care and type of prescription drugs.

The data source regarding the demographic characteristics, clinical symptoms, laboratory, and radiological findings on admission as well as the complications, treatment, and outcomes during hospitalization were gathered from their medical record through two trained nurses and was modified according the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) (10) .

The variables registered included demographic data, epidemiological information, comorbidities (chronic cardiac disease, chronic pulmonary disease, cancer, hypertension and chronic liver disease), baseline laboratory tests result (hemoglobin lymphocyte count, platelet count), signs J o u r n a l P r e -p r o o f and symptoms at admission (fever, cough, dyspnea, myalgia and headache) and outcome including mortality in hospital.

Logistic regression (LR):

LR is an exceedingly popular classical statistical technique used for classifications type prediction problems, has traditionally been the choice of many studies to determine the relationship between target variable of with a set of independent variables (11) . The model can be present as follows: The mean (SD) age of the case group was higher than that of the control group; [65. 24 (12.40) years vs. 59.35 (17.34) years, respectively (P<0.001)]. In addition, the proportion of females was significantly higher in case than in control (57.1% versus 43.6%; P<0.001). The details of cases and controls, including demographic characteristics, epidemiological information, comorbidities, signs and symptoms at admission and laboratory tests results are shown in Table 1 . As shown, two groups were heterogenic in regards of gender, headache and fever sign, cardiovascular and hypertension co-morbidity, and ESR, BUN, BS, NA, K, HCT and Hb markers (P<0.05).

The effect of various potential risk factors for mortality of COVID-19 in diabetic AND nondiabetic patients is given in tables 2 and 3 using crude (table 2) In this study we analyzed the demographic characteristics, epidemiological information, comorbidities, signs and symptoms at admission and laboratory tests results of COVID-19 patients with diabetes compared COVID-19 patients without diabetes and identified the risk factors associated with in-hospital death of these patients. In this study we found that in COVID-19 patients with diabetes advanced age, addiction, high level of BUN and Alp and in nondiabetic COVID-19 patients advanced age, dyspnea, high level of BUN and SGOT were associated with increase risk of death in these patients.

Similar to our study, in previous studies advaned age has been considered as a risk factor of death in non-diabetic COVID-19 patients and also in COVID-19 patients with diabete type 1 and 2 diabetes(13). In Cheng et al study age older than 60 years was identified as a independent risk factors for serious disease in SARS-CoV-2 infection (14) . Tehrani and collagenous revealed that advanced age contribute to a fatal outcome in hospitalized COVID-19 patients (15) . It has been shown that high mortality rate of elderly patients with COVID-19 is mainly due to the frequent occurrence of multiple comorbidities including but not limited to hyperglycemia (16) .

We observed that non-diabetic COVID-19 patients with dyspnea were significantly more likely to die than patients without dyspnea. Dyspnea is a sign of respiratory disease, so can be an important risk factor for progression COVID-19 to advanced stages (17) . Shi et al, reported that presence of dyspnea was a risk factors for death in SARS-CoV-2 infection (18) .It has been reported in several studies that COVID-19 patients with dyspnea had a higher risk for hospitalization, ICU addmission, mechanical ventilation, severe disease, disease progression and mortality than those without dyspnea (19) (20) (21) (22) .

Other finding of present study showed that addiction is a risk factor of death in COVID-19 patients with diabetes. It may be because patients with diabetes are at higher risk of receiving polypharmacy than patiens without diabetes. So, addicted patiens with diabetes have increased risks of adverse drug events (23) . In this regard, Baillargeon In our study, high ALP and SGOT (AST) levels respectively in diabetic and non-diabetic patients were associated with increased risk of COVID-19 related death. Both of these enzymes are indicators of liver damage and dysfunction, which can be seen in more than half of patients with COVID-19 (29) . It has been shown that the SARS-CoV-2 virus may also bind to ACE2 on cholangiocytes and induce a systemic inflammatory response leading to liver injury (30) . Also, it has been suspected that some detrimental effects on liver injury is mainly due to certain medications used during COVID-19 hospitalization (31) . In agreement with our findings, Pazoki et al. showed that high serum levels of ALP and AST was a risk factor of in-hospital mortality and disease severity in diabetic patients with confirmed or clinically suspected COVID-19 (27) . (32) . However, liver damage and increased levels of liver enzymes in serum including AST and ALP is also reported in the diabetic patients in Islam et al study (33) .

Limitations of this study include the following: first, due to the retrospective nature of the study, we could not assess all clinical and laboratory information such as d-dimer for all patients.

Secondly, in this study we included only hospitalized patients with relatively severe symptoms and patients with mild or moderate symptoms were not assessed in the present study.

We found that in COVID-19 patients with diabetes; advanced age, addiction, high level of BUN and Alp and in non-diabetic COVID-19 patients advanced age, dyspnea, high level of BUN and SGOT were associated with increase risk of death in these patients. J o u r n a l P r e -p r o o f 

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