During the early phase of the COVID-19 pandemic, Dubai Hospital, where the study was conducted, was among the three main centers designated for the isolation and admission of all patients with COVID-19 in the Emirate of Dubai. Dubai Hospital is a specialized hospital equipped with 625 beds and incorporates 26 surgical and medical departments, including the intensive care unit (ICU), cardiology, oncology, nephrology, and endocrinology. During the first wave of the COVID-19 pandemic, most hospital wards were converted into isolation units. In this cross-sectional nested case-control study, 1083 patients with COVID-19 admitted to Dubai Hospital between March 21^st and September 30^th, 2020, were recruited.

All patients positive for COVID-19 were admitted to hospital. Patients were tested using reverse transcription-polymerase chain reaction (RT-PCR) using a nasopharyngeal swab for respiratory tract infection to test for COVID-19. A total of 1083 patients were randomly recruited for the study. This study included 890 men and 193 women. Of these patients, 427 had T2D and 656 did not.

Patients with type 1 diabetes were excluded. This was based on their previous medical history collected from the SALAMA Electronic Health Records (EHR) and confirmed upon admission. The following clinical data were obtained from the EHR: Age (13–87 years), sex (men/women), nationality (emirates/expatriates), and comorbidities [hypertension, ischemic stroke, cardiomyopathy, heart failure, chronic obstructive pulmonary disease, asthma, and diabetic ketoacidosis]. The following presenting symptoms were recorded at admission: Fever, cough, shortness of breath, sore throat, chest pain, myalgia, headache, chills, fatigue, malaise, loss of appetite, runny nose, abdominal pain, loss of taste, loss of smell, vomiting, diarrhea, dizziness, confusion, skin rash, and arthralgia. Noninvasive ventilation, intubation, and admission to the ICU were also recorded.

The mean ages of the patients were 51 and 39 years for those with and without T2D, respectively. Demographic features and the presence of co-morbidities, such as a prior diagnosis of cardiac disease, hypertension, diabetes, or respiratory disease, and any medication used were recorded. Patients were further categorized as asymptomatic, mild, moderate, severe, or critical according to the National Institutes of Health categorization of COVID-19 severity[26], as follows:

Asymptomatic: Patients have no symptoms but have tested positive for COVID-19.

Mild: Patients have symptoms and signs such as fever, cough, sore throat, malaise, headache, or muscle pain, but no shortness of breath, dyspnea, or abnormal chest radiography.

Moderate: Patients had clinical or imaging findings suggestive of lower respiratory disease but maintained an oxygen saturation of > 93% on room air.

Severe: The respiratory rate (RR) of the patients was above 30/min, oxygen saturation was ≤ 93%, PaO2/FiO2 was < 300, and/or pneumonic infiltrates involving > 50% of the lungs were observed.

Critical: Patients suffer respiratory failure, septic shock, and/or multiple organ dysfunction.

The vital signs recorded at the time of admission included blood pressure, heart rate, RR, SpO₂, and temperature.

Data were collected from all patients with and without T2D from the Dubai Hospital SALAMA Electronic Medical Record System. The information collected was categorized into demographic data, medical and glycemic histories, physical examination results, comorbidities, laboratory investigation results, chest radiographs, complications, and treatment protocols. The collected data were entered into an SPSS data collection sheet explicitly designed for this study. All patient data were de-identified throughout the collection, categorization, and creation of the database. The reporting of this study conformed to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines[27].

Laboratory measurements recorded for patients with COVID-19 included complete blood count, ferritin, absolute lymphocyte count, lactate dehydrogenase, procalcitonin, C-reactive protein (CRP), creatine phosphokinase, D-dimer, pro-BNP, serum creatinine, fasting blood glucose, and Hb_A1C.

Chest X-ray scoring: A chest radiograph severity scoring system was used to determine the severity of the pneumonia. The images were also classified as exhibiting ground-glass opacities, reticular patterns, or consolidations and as normal, mild, moderate, or severe.

The management and Treatment of COVID-19 followed the United Arab Emirates Guidelines[28]. which are based on the National Institutes of Health (NIH) guidelines (NIH, 2021)[29]. After a thorough assessment of clinical severity, all patients with COVID-19 were treated (March–September 2020) with a standard combination of hydroxychloroquine sulfate and Kaletra antiviral (lopinavir/ritonavir). Therefore, there were no differences in drug management between patients with and without T2D. Patients were considered cured after two consecutive negative (determined through RT-PCR) nasopharyngeal swabs following clinical recovery.

Data were analyzed using SPSS for Windows version 28.0 (SPSS Inc., Chicago, IL, United States). Categorical variables are described as percentages. Continuous variables were described using a measure of tendency and dispersion. Continuous data were tested for normality using the Kolmogorov-Smirnov test. The Mann-Whitney U test and t-test were used when appropriate to compare the means between continuous variables. Categorical variables were cross-tabulated to examine the independence between variables, the χ² test or Fisher’s exact test was used as appropriate.

Kaplan-Meier estimates were used to examine the effect of T2D on survival. The estimate was based on the serial time to death of patients with T2D and controls. The results of the computed model are visualized in a survival plot (Figure 1). In addition to the Kaplan-Meier analysis, univariate and multivariate analyses containing all the variables that differed statistically between survivors and non-survivors were performed to identify the independent predictors of mortality among patients with COVID-19 and T2D. Statistical significance was set at P < 0.05.

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Figure 1  The Kaplan-Meier plot relating survival against serial time to death between coronavirus disease 2019 patients with and without type 2 diabetes. T2D: Type 2 diabetes.

A total of 1083 patients (890 men and 193 women) diagnosed with COVID-19 were enrolled in this study. Among the men, 378 (42%) had T2D, whereas among the women, only 49 (25%) had T2D. The mean age of patients with T2D is 51.4 (± 11.2), whereas for patients without T2D is 39.4 (± 13.5) (P < 0.001). There was also a significant difference in BMI between patients with T2D [28.80 (± 5.47)] compared to patients without T2D [27.20 (± 4.94)] (P < 0.001).

The demographic characteristics and comorbidities of patients with T2D and patients without are shown in Table 1. Patients with T2D and COVID-19 had higher rates of comorbidities, such as hypertension, ischemic heart disease, and heart failure compared to patients with COVID-19 without T2D.

Only dyspnea, cough, sore throat, and headache were significantly more frequent in patients with T2D (Table 1).

All 18 Laboratory measurements indicative of disease severity were significantly higher among patients with T2D (Table 1).

Chest radiographs of patients with COVID-19 and T2D exhibited significantly more lung consolidation, ground-glass appearance, and severity than patients without (Table 1). Consequently, COVID-19 patients with T2D had significantly lower SpO₂ saturation and required more noninvasive assisted ventilation as well as frequent mechanical ventilation. They also had more life-threatening complications, such as diabetic ketoacidosis and acute kidney failure. Therefore, these patients had longer hospital stays and significantly higher mortality rates.

All patients with COVID-19 were treated (March-September 2020) with a standard combination of hydroxychloroquine sulfate and Kaletra antiviral medication (lopinavir/ritonavir). Therefore, there were no differences in drug management between patients with and without T2D.

In general, patients with COVID-19 with T2D were 12 years older than those without T2D (Table 1). In addition, non-survivors were older than survivors in both groups (Table 2). On admission, there were no significant differences in the symptoms between the two groups.

Most laboratory indicators of disease severity were equally high among the COVID-19 non-survivors in each group (Table 2). The association of radiographic and severity indices of chest infection with mortality in patients with COVID-19 was also equally high among the patients in each group. Therefore, most risk factors for severity and predictors of mortality in T2D non-survivors and controls were similar, with few exceptions (Table 2).

The relationship between random blood glucose, fasting blood glucose and blood Hb_A1C, and mortality among patients with COVID-19 and T2D was tested using the Mann-Whitney U test and found to be statistically insignificant.

Predictors of mortality were determined in non-survivors of COVID-19 with and without T2D, using univariate analysis. Among the eight clinical and 12 Laboratory risk factors (Table 2), significant associations of mortality of COVID-19 in patients with and without T2D were identified with advanced age, increased total white blood cell (WBC) count, lymphopenia, and elevated serum troponin. In multivariate analysis, only lymphopenia was identified as a predictor of mortality in patients with T2D.

Kaplan-Meier analysis was used to compare survival against serial time to death between patients with and without T2D (Figure 1). The median time of death among patients without T2D is less than that among patients with T2D [42 d with 95%CI: 32.2–51.8 and 54 d with 95%CI (23.3–84.7)]; respectively. This difference was not statistically significant because 95% of the CIs overlapped. However, the number of deaths was significantly higher among patients with T2D [63 (14.8%)] than among patients without T2D [36 (5.5%)], with P < 0.001 (Table 3).

The overall ratio of COVID-19 patients who died among patients with T2D was three times that of patients without T2D (Table 3). The ratio remained high in each successive 5-d interval for the first 4 wk of admission but decreased thereafter.

The authors acknowledge the several limitations of this study. It is possible that there was a selection bias in this study, as it was a short-term cross-sectional nested case-control study in which data were collected over a short period in a pandemic environment. In this cross-sectional study, it was not possible to establish causal inferences or analyze temporal changes. Patients could not be followed-up with after discharge, limiting the possibility of further outcomes. Despite these limitations, this study provided data on a large cohort of patients with COVID-19 and T2D with results similar to those of many internationally acknowledged studies.

Patients with diabetes suffer higher morbidity and mortality from corona virus disease 2019 (COVID-19). Despite better outcomes due to vaccination, many patients with diabetes continue to suffer from the disease. It is imperative therefore, to continue investigating the risk and predictors of COVID-19 severity in this vulnerable group, to help shaping better management of the disease.

Identifying independent predictors of mortality from COVID-19 will allow healthcare workers to prioritize vaccination, implement early management strategies for patients with COVID-19 and type 2 diabetes (T2D), and offset disease severity and mortality.

To identify independent mortality predictors among in-hospital patients with COVID-19 and T2D during the first wave of the pandemic (March–September 2020) in Dubai, United Arab Emirates.

In this cross-sectional nested case-control study, a total of 1083 patients with COVID-19 were recruited. Of these, 427 had T2D and 656 were non-diabetic. The clinical, radiographic, and laboratory data of the patients with and without T2D were compared. Independent predictors of mortality in COVID-19 non-survivors were identified in patients with and without T2D.

Patients with T2D and COVID-19 were older and had a higher body mass index than patients without T2D. They had higher rates of comorbidities such as hypertension, ischemic heart disease, heart failure, and more life-threatening complications. All laboratory parameters of disease severity were significantly higher than in those without T2D. Therefore, these patients had a longer hospital stay and a significantly higher mortality rate. These patients died from COVID-19 at three times the rate of patients without T2D. In the univariate analysis of the independent predictors of mortality among all COVID-19 non-survivors, significant associations were identified with old age, increased white blood cell count, lymphopenia, and elevated serum troponin levels. In multivariate analysis, only lymphopenia was identified as an independent predictor of mortality among T2D non-survivors.

It seems that the increased severity and mortality of patients with COVID-19 and T2D is due to older age and comorbidities such as hypertension, cardiovascular disease, chronic kidney disease, and obesity, with an added severe proinflammatory state.

It is necessary to further investigate the factors that heighten the pro-inflammatory state, driving higher mortality among patients with T2D and COVID-19.