Introduction: We aimed to evaluate the clinical characteristics of patients presenting with DKA and COVID-19 infection and describe the clinical outcomes compared to those without COVID-19. Methods: A retrospective study in a single tertiary care hospital in Dubai was conducted on patients admitted between 1st March 2020 and 30th July 2020 with a diagnosis of DKA with and without COVID-19 infection. Results: A total of 32 patients with DKA were identified. Eleven patients had a positive COVID-19 test and 21 patients were negative. The majority of DKA patients were males (84.4%). In the COVID-19 group, the mean age was 41.3 years old. Seven patients had preexisting diabetes (63.7%) and 4 patients (36.4%) had newly diagnosed diabetes. COVID-19 patients had a longer median length of hospital stay (7 days vs. 4 days; p = 0.278), shorter duration of DKA (16 h vs. 24 h; p = 0.043), and higher mortality (18.2% vs. 0%; p = 0.047). Conclusion: COVID-19 infection can precipitate DKA in patients with either newly diagnosed or preexisting diabetes. DKA patients with COVID-19 infection had higher mortality compared to those without COVID-19. This should urge physicians to be more vigilant in assessing the glycemic status of patients presenting with COVID-19 infection.

In December 2019, SARS-CoV-2 was identified as the pathogen causing coronavirus disease (COVID-19) in Wuhan, China [1]. On March 11th, 2020, COVID-19 was announced as a pandemic by the World Health Organization [1]. In the United Arab Emirates, the first case was detected on January 29th, 2020, after which there was a gradual upsurge of cases.

Current epidemiological reports show a close association between diabetes and COVID-19 infection with an increased likelihood of complications and mortality [2]. On the other hand, the coexistence of hypertension, obesity, and cardiovascular disease in patients with diabetes may also contribute to the increased risk of morbidity and mortality [3].

The clinical characteristics of patients with diabetes admitted with SARS-CoV-2 infection and their outcomes have been widely reported. However, as the burden of diabetes in our region remains high, it remains important to examine this association in our population.

A retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed COVID-19 infection at Zhongnan Hospital of Wuhan from January 1 to January 28, 2020; 22.2% of ICU care admissions were for patients with diabetes [4]. In a parallel Chinese retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital between December 2019 and January 2020, 41.8% developed acute respiratory distress syndrome (ARDS), out of which 19.0% had diabetes. Those patients with diabetes had severe complications and mortality secondary to ARDS (hazard ratio = 1.58) [5].

DKA is the most common hyperglycemic crisis and life-threatening complication of diabetes [6]. DKA has been reported in COVID-19, as with other infections, in both T1D and T2D [7]. In one prospective observational study of 93 patients with diabetes, conducted in the department of medicine of a tertiary health care hospital in Karachi, Pakistan from July to December 2018, the commonest risk factor for DKA development was underlying infection compared with other risk factors [8].

In this study, we investigated the clinical characteristics and laboratory tests of all patients admitted to our tertiary hospital with DKA during the COVID-19 pandemic, with and without COVID-19 infection. The data from this study will highlight knowledge gaps that require further research and studies pertinent to DKA in patients with COVID-19 infection.

Study Design and Population

This is a retrospective observational study in a single tertiary care hospital in Dubai, United Arab Emirates on patients admitted between March 1st, 2020, and July 30th, 2020, with laboratory-confirmed DKA upon presentation with and without COVID-19 infection. Our inclusion criteria were defined as (1) age above 18 years old; (2) patients who fulfilled the DKA definition; (3) COVID-19 test whether it is negative or positive. The exclusion criteria were (1) pregnancy and (2) age less than 18 years old.

Definitions

A confirmed case of COVID-19 infection was defined as a positive result on polymerase chain reaction of a nasopharyngeal specimen swab. All patients who tested positive for SARS-CoV-2 also had radiological imaging with a chest X-ray as per the hospital policy. DKA was defined as: blood glucose level >250 mg/dL, serum bicarbonate <18 mmol/L, serum pH <7.3, and blood ketones >3 mmol/L [9].

DKA severity was defined as mild by a pH of 7.25–7.29 and/or a bicarbonate level between 15 and 17.9 mmol/L and an anion gap >10; moderate by a pH of 7.0–7.24 and/or a bicarbonate level between 10 and 14.9 mmol/L and an anion gap >12; and severe by a pH of 7.0 and or a bicarbonate level between 10 and 14.9 mmol/L and an anion gap >12 without coma or DKA with altered conscious level: DKA coma. This classification is as per the ADA consensus on acute complications of diabetes in 2009 [9]. The duration of DKA was defined by the time of resolution of acidosis and ketosis when the serum bicarbonate level is > 18 mmol/L, pH >7.3, and blood ketones <0.3 mmol/L [9].

COVID-19 severity was classified as mild, moderate, severe, and critical based on the living guidelines of the WHO publication for “Clinical Management of COVID-19” [10]. Mild COVID-19 is defined as symptomatic patients without evidence of pneumonia or hypoxia; moderate disease is defined as clinical signs and symptoms of pneumonia with SpO2 >90% on room air; severe disease is defined as clinical signs and symptoms of pneumonia with SpO2 <90% on room air; and critical disease is associated with ARDS, sepsis, septic shock, or acute thrombosis [10].

Data Collection

Clinical, laboratory parameters, and demographic data were obtained from the electronic medical records of admitted patients, including the baseline patient’s characteristics, type of diabetes, HbA1c level, antidiabetic medications, predisposing factors, comorbidities, Glasgow Coma Scale (GCS), vital signs at admission, chest X-ray findings, oxygen requirements, blood glucose, pH, serum bicarbonate, blood ketone, ferritin, lactate dehydrogenase, D-Dimer and C-reactive protein, lactic acid, renal parameters, duration of DKA, duration of hospital stay, complications, and outcome. All the chest X-rays were viewed and reported by radiologists within our facility.

Statistical Analysis

Data analysis was performed using the SPSS software version 24. Numerical variables were presented as median with interquartile range (IQR) for skewed data and as mean ± SD for data with normal distribution. Categorical variables were presented as total numbers with percentages. The comparison of parameters between groups (COVID-19 positive and COVID-19 negative) was made using the Mann-Whitney test for variables with a skewed distribution, t test for variables with normal distribution, the χ2 test, and Fisher’s exact test for categorical variables. A p value of <0.05 was considered significant. Kolmogorov-Smirnov test was used to test for normality.

A review of the electronic medical records of all the patients admitted with DKA identified a total of 32 patients from March to July 2020. Eleven patients had a laboratory confirmed COVID-19 infection diagnosed on real-time reverse transcription-polymerase chain reaction assays, and 21 patients were negative.

Demographics and clinical characteristics of patients with DKA according to their COVID-19 status are summarized in Table 1.

Table 1.

Demographics and clinical characteristics of patient with DKA according to their COVID-19 status

ParametersCOVID-19 positive group (n = 11)COVID-19 negative group (n = 21)p value
Gender, n (%) 0.777 
 Male 9 (81.8) 18 (85.7) 
 Female 2 (18.2) 3 (14.3) 
Age, mean±SD, years 41.3±11.9 33.71±14.7 0.091 
Ethnicity, n (%) 0.517 
 Asian 9 (81.8) 13 (61.9) 
 Middle East 3 (14.3) 
 Africa 2 (18.2) 4 (19) 
 Others 1 (4.8) 
BMI, n (%) 0.080 
 Underweight 1 (4.8) 
 Normal 9 (81.8) 8 (38.1) 
 Overweight 2 (18.2) 10 (47.6) 
 Obese 2 (9.5) 
Type of diabetes, n (%) 0.725 
 Type 1 3 (27.3) 4 (19) 
 Type 2 4 (36.4) 13 (61.9) 
 Newly diagnosed 4 (36.4) 4 (19) 
Antidiabetic medications 0.481 
 Nil 4 (36.4) 6 (28.6) 
 Oral hypoglycemic agents 4 (36.4) 5 (23.8) 
 Oral and insulin 0 (0.0) 2 (9.5) 
 Insulin 3 (27.3) 8 (38.1) 
Comorbidities, n (%) 0.599 
 No 8 (72.7) 17 (81) 
 Yes 3 (27.3) 4 (19) 
Predisposing factors, n (%) 0.197 
 Nil 2 (18.2) 7 (33.3) 
 Noncompliance 3 (27.3) 9 (42.9) 
 Infection 6 (54.5) 4 (19) 
 Others: alcohol, myocardial infarction 0 (0.0) 1 (4.8) 
ParametersCOVID-19 positive group (n = 11)COVID-19 negative group (n = 21)p value
Gender, n (%) 0.777 
 Male 9 (81.8) 18 (85.7) 
 Female 2 (18.2) 3 (14.3) 
Age, mean±SD, years 41.3±11.9 33.71±14.7 0.091 
Ethnicity, n (%) 0.517 
 Asian 9 (81.8) 13 (61.9) 
 Middle East 3 (14.3) 
 Africa 2 (18.2) 4 (19) 
 Others 1 (4.8) 
BMI, n (%) 0.080 
 Underweight 1 (4.8) 
 Normal 9 (81.8) 8 (38.1) 
 Overweight 2 (18.2) 10 (47.6) 
 Obese 2 (9.5) 
Type of diabetes, n (%) 0.725 
 Type 1 3 (27.3) 4 (19) 
 Type 2 4 (36.4) 13 (61.9) 
 Newly diagnosed 4 (36.4) 4 (19) 
Antidiabetic medications 0.481 
 Nil 4 (36.4) 6 (28.6) 
 Oral hypoglycemic agents 4 (36.4) 5 (23.8) 
 Oral and insulin 0 (0.0) 2 (9.5) 
 Insulin 3 (27.3) 8 (38.1) 
Comorbidities, n (%) 0.599 
 No 8 (72.7) 17 (81) 
 Yes 3 (27.3) 4 (19) 
Predisposing factors, n (%) 0.197 
 Nil 2 (18.2) 7 (33.3) 
 Noncompliance 3 (27.3) 9 (42.9) 
 Infection 6 (54.5) 4 (19) 
 Others: alcohol, myocardial infarction 0 (0.0) 1 (4.8) 
The clinical and biochemical findings in the COVID-19 positive group were as follows: the mean age was 41.3 ± 11.9 years. Nine patients are male and 2 patients are female. As for ethnicity, nine were Asian (81.8%) and two were African (18.2%). Only 2 patients (18.2%) had a BMI in the overweight range, and 9 patients (81.8%) had a normal BMI. Of the 11 patients, 3 patients (27.3%) had preexisting T1D, 4 patients (36.4%) had preexisting T2D, and 4 patients (36.4%) were newly diagnosed with diabetes. Four patients (36.4%) were not on any antidiabetic medications; 4 patients (36.4%) were on oral hypoglycemic agents; and three (27.3%) were on insulin. Eight patients (72.7%) have no associated comorbidities apart from diabetes. Predisposing factors for DKA were underlying infection 54.5% followed by medications noncompliance 27.3% and in 18.2% no clear cause was identified but were newly diagnosed diabetes mellitus.

Five out of 11 (45.5%) had moderate COVID-19 infection, 4 patients (36.4%) had asymptomatic disease, 1 patient (9.1%) had severe infection, and 1 patient (9.1%) had critical infection.

Presenting symptoms of DKA patients in both COVID-19 positive and COVID-19 negative groups are summarized in Table 2.

Table 2.

Presenting symptoms of DKA patients in both COVID-19 positive and COVID-19 negative groups

SymptomsCOVID-19 positive (n = 11)COVID-19 negative (n = 21)
Fever 3 (27.3) 5 (23.8) 
Upper respiratory tract infection 1 (9.1) 1 (4.8) 
Respiratory symptoms 5 (45.5) 7 (33.3) 
Gastrointestinal symptoms 6 (54.4) 15 (71.4) 
Weight loss 4 (36.4) 2 (9.5) 
Fatigue 4 (36.4) 4 (20) 
Osmotic symptoms* 4 (36.4) 9 (42.9) 
SymptomsCOVID-19 positive (n = 11)COVID-19 negative (n = 21)
Fever 3 (27.3) 5 (23.8) 
Upper respiratory tract infection 1 (9.1) 1 (4.8) 
Respiratory symptoms 5 (45.5) 7 (33.3) 
Gastrointestinal symptoms 6 (54.4) 15 (71.4) 
Weight loss 4 (36.4) 2 (9.5) 
Fatigue 4 (36.4) 4 (20) 
Osmotic symptoms* 4 (36.4) 9 (42.9) 

n is the number of patients and the values in parentheses are percentages.

*Osmotic symptoms: polydipsia, polyuria, weight loss.

The main presenting symptoms in both groups were gastrointestinal symptoms in the form of vomiting and abdominal pain (54.4% in COVID-19 and 71.4% in non-COVID-19), followed by respiratory symptoms in the COVID-19 positive group (45.5%) and osmotic symptoms in the COVID-19 negative group (42.9%).

Laboratory parameters of both COVID-19 positive and COVID-19 negative DKA patients are summarized in Table 3.

Table 3.

Laboratory parameters of both COVID-19 positive and COVID-19 negative DKA patients

ParametersCOVID-19 positiveCOVID-19 negativep value
HBA1C%, mean±SD 13.5±3.061 12.8±2.148 0.688 
LDH, U/L, mean±SD 279.4±120 289.6±186 0.650 
Bicarbonate mmol/L, mean±SD 8.2±3.26 8.6±3.99 0.874 
pH, median (IQR) 7.20 (0.10) 7.1 (0.20) 0.483 
Blood glucose, mg/dL, median (IQR) 484 (282) 429 (201) 0.077 
Creatinine, mg/dL, median (IQR) 1.3 (0.8) 1 (0.8) 0.320 
Urea, mg/dL, median (IQR) 50 (97) 36 (34) 0.062 
Blood ketone, mmol/L, median (IQR) 6.7 (1.8) 6.0 (2.4) 0.886 
CRP, mg/L, median (IQR) 50.2 (111.6) 10 (94) 0.237 
Ferritin, ng/mL, median (IQR) 459 (393) 419 (571) 0.705 
Dimer, μg/mL, median (IQR) 1.0 (3.0) 0.690 (4.44) 0.515 
Lactic acid, mmol/L, median (IQR) 2.40 (1.2) 2.0 (1.5) 0.241 
ParametersCOVID-19 positiveCOVID-19 negativep value
HBA1C%, mean±SD 13.5±3.061 12.8±2.148 0.688 
LDH, U/L, mean±SD 279.4±120 289.6±186 0.650 
Bicarbonate mmol/L, mean±SD 8.2±3.26 8.6±3.99 0.874 
pH, median (IQR) 7.20 (0.10) 7.1 (0.20) 0.483 
Blood glucose, mg/dL, median (IQR) 484 (282) 429 (201) 0.077 
Creatinine, mg/dL, median (IQR) 1.3 (0.8) 1 (0.8) 0.320 
Urea, mg/dL, median (IQR) 50 (97) 36 (34) 0.062 
Blood ketone, mmol/L, median (IQR) 6.7 (1.8) 6.0 (2.4) 0.886 
CRP, mg/L, median (IQR) 50.2 (111.6) 10 (94) 0.237 
Ferritin, ng/mL, median (IQR) 459 (393) 419 (571) 0.705 
Dimer, μg/mL, median (IQR) 1.0 (3.0) 0.690 (4.44) 0.515 
Lactic acid, mmol/L, median (IQR) 2.40 (1.2) 2.0 (1.5) 0.241 
Laboratory parameters in the COVID-19-positive patients revealed mean HbA1c: 13.5 ± 3.06%, mean lactate dehydrogenase: 279 ± 120 U/L, median plasma glucose: 484 mg/dL (IQR: 282), median creatinine: 1.3 mg/dL (IQR: 0.8), median ferritin: 459 ng/mL (IQR: 393), median D-Dimer: 1 μg/mL (IQR: 3.0), median lactic acid: 2.4 mmol/L (IQR: 1.2), and median C-reactive protein: 50.2 mg/L (IQR: 111.6). But none of these biochemical parameters at presentation was significantly different between the COVID-19 positive and negative groups.

DKA severity, duration, length of hospital stay, complications, and outcomes in COVID-19 positive and negative groups are summarized in Table 4.

Table 4.

DKA severity, duration, length of hospital stay, complications, and outcomes in COVID-19 positive and negative groups

ParametersCOVID-19 positive group (n = 11)COVID-19 negative group (n = 21)p value
DKA severity, n (%) 0.370 
 Mild 0 (0.0) 2 (9.5) 
 Moderate 4 (36.4) 8 (38.1) 
 Severe 7 (63.6) 11 (52.4) 
Duration of DKA, mean±SD, h 17.5±10.8 31±20.9 0.043 
Length of hospital stay, mean±SD, days 7.55±6.5 6.38±5.9 0.278 
Complications, n (%) 0.489 
 Nil 9 (81.8) 19 (90.5) 
 Intubation, ICU admission 2 (18.2) 2 (9.5) 
Outcomes, n (%) 0.047 
 Discharged 9 (81.8) 21 (100) 
 Deceased 2 (18.2) 0 (0.0) 
ParametersCOVID-19 positive group (n = 11)COVID-19 negative group (n = 21)p value
DKA severity, n (%) 0.370 
 Mild 0 (0.0) 2 (9.5) 
 Moderate 4 (36.4) 8 (38.1) 
 Severe 7 (63.6) 11 (52.4) 
Duration of DKA, mean±SD, h 17.5±10.8 31±20.9 0.043 
Length of hospital stay, mean±SD, days 7.55±6.5 6.38±5.9 0.278 
Complications, n (%) 0.489 
 Nil 9 (81.8) 19 (90.5) 
 Intubation, ICU admission 2 (18.2) 2 (9.5) 
Outcomes, n (%) 0.047 
 Discharged 9 (81.8) 21 (100) 
 Deceased 2 (18.2) 0 (0.0) 
COVID-19 patients compared to non-COVID-19 patients had a longer median length of hospital stay (median [IQR]; 7 [5] days vs. 4 [8] days: p = 0.278), but this was not statistically significant. They also had a shorter duration of DKA (median [IQR]; 16 [6] hours vs. 24 [26] hours; p = 0.043) and higher mortality (18.2% vs. 0%; p = 0.047).

The majority of patients in both groups did not develop complications (87.5%), while 12.5% required interventions such as intubation, mechanical ventilation, and/or ICU admission. Out of the total 32 patients in both groups, 30 patients were discharged (93.8%) and 2 patients died (6.3%).

The clinical profile of DKA patients who required ICU admission based on their COVID-19 status is summarized in Table 5.

Table 5.

The clinical profile of DKA patients who required ICU admission based on their COVID-19 status

ParametersCOVID-19 positive groupCOVID-19 negative group
patient 1patient 2patient 1patient 2
Intubation Yes Yes No No 
DKA severity Severe Severe Severe Severe 
COVID-19 severity Critical Severe NA NA 
Outcome Deceased Deceased Discharged Discharged 
Duration of DKA, h  16 48 32 60 
Length of hospital stay, days 9  5  8  5  
Age, years 52 55 32 18 
Gender Male Male Male Male 
Ethnicity Asian Asian Asian Asian 
BMI, kg/m2 29 24 28 34 
Type of diabetes Preexisting type 2 Newly diagnosed type 2 Preexisting type 2 diabetes Newly diagnosed type 1 
HBA1C% 9.8 13.4 12.7 
Predisposing factors Infection Infection Medications noncompliance Newly diagnosed diabetes 
Comorbidities:  other than diabetes Nil Nil Nil Nil 
Presenting  symptoms Respiratory symptoms Respiratory symptoms Osmotic symptoms Osmotic symptoms 
pH 6.8 
Bicarbonate,  mmol/L 8.8 5.5 3.6 6.3 
Blood glucose,  mg/dL 389 425 641 301 
Creatinine, mg/dL 0.9 1.4 2.2 0.7 
CRP, mg/L 130 221 5.8 26 
Dimer, μg/mL 1.9 3.5 2.52 Not done 
Lactic acid, mmol/L 1.7 2.6 3.5 
ParametersCOVID-19 positive groupCOVID-19 negative group
patient 1patient 2patient 1patient 2
Intubation Yes Yes No No 
DKA severity Severe Severe Severe Severe 
COVID-19 severity Critical Severe NA NA 
Outcome Deceased Deceased Discharged Discharged 
Duration of DKA, h  16 48 32 60 
Length of hospital stay, days 9  5  8  5  
Age, years 52 55 32 18 
Gender Male Male Male Male 
Ethnicity Asian Asian Asian Asian 
BMI, kg/m2 29 24 28 34 
Type of diabetes Preexisting type 2 Newly diagnosed type 2 Preexisting type 2 diabetes Newly diagnosed type 1 
HBA1C% 9.8 13.4 12.7 
Predisposing factors Infection Infection Medications noncompliance Newly diagnosed diabetes 
Comorbidities:  other than diabetes Nil Nil Nil Nil 
Presenting  symptoms Respiratory symptoms Respiratory symptoms Osmotic symptoms Osmotic symptoms 
pH 6.8 
Bicarbonate,  mmol/L 8.8 5.5 3.6 6.3 
Blood glucose,  mg/dL 389 425 641 301 
Creatinine, mg/dL 0.9 1.4 2.2 0.7 
CRP, mg/L 130 221 5.8 26 
Dimer, μg/mL 1.9 3.5 2.52 Not done 
Lactic acid, mmol/L 1.7 2.6 3.5 

NA, not applicable.

Two out of the 11 DKA COVID-19 patients required intubation and ICU admission, and both died. One had a severe COVID-19 infection and the other one had a critical disease. Both had severe DKA and presented with respiratory symptoms related to the COVID-19 infection. They were males, Asian, aged in their 50 s with no associated comorbidities apart from underlying T2D. Both patients were observed to have higher levels of C-reactive protein and one had a higher dimer level. They developed complications such as ARDS and renal failure. While in the COVID-19 negative group, 2 out of 21 patients required ICU admission related to severe DKA but did not require intubation, and both survived. Both had severe DKA and presented with osmotic symptoms.

The current study is a retrospective observational study that examined the clinical profile of patients presenting with DKA and COVID-19 infection, in addition to the difference in mortality, length of hospital stay, DKA status, complications, and outcomes compared to those without COVID-19 infection. The majority of our patients admitted with DKA were males and of Asian ethnicity, with a mean age of 41.3 years in the COVID-19 positive group and 33.7 years in the COVID-19 negative group, which is much younger than the age reported in a previous study [11]. These findings are a reflection of the United Arab Emirates population demographics, which showed that 75% are of Asian ethnicity, 72% are males, and 65% are in the age group of 25–54 years [12]. Most of the patients in both groups had a normal BMI since the majority of our patients are of Asian ethnicity. Our findings match with the scientific evidence that Asian populations are at a high risk of T2D and its complications at BMIs lower than the existing WHO cut-off point [13].

Although DKA is more likely to happen in T1D, it is documented that the majority of DKA cases worldwide occur in patients with T2D due to its higher prevalence [14]. Moreover, DKA more frequently occurs in people with established diabetes than at the time of diagnosis, probably because of increased diabetes screening and early recognition [6]. In our study, we found that out of 11 patients in the COVID-19 positive group, 3 patients (27.3%) had a history of T1D, 4 patients (36.4%) had preexisting T2D, and 4 patients (36.4%) were newly diagnosed with T2D. Heaney et al. [15]. described a 54-year-old male with newly diagnosed T2D presenting as DKA and COVID-19 infection Soe et al. [8] reported 2 cases of DKA and COVID-19 that were known to have T2D.

Infection is a well-documented predisposing factor for DKA [16]. During the pandemic in patients with diabetes, whether infected with COVID-19 or not, noncompliance is another predisposing factor which is related to potential lapses in access to medicines or their care team [2]. This was demonstrated in our study, which showed that the most common precipitating factors for DKA in the COVID-19 positive group were underlying infection (54.5%), followed by medication noncompliance (27.3%), while in the COVID-19 negative group, noncompliance was the main predisposing factor (42.9%). This finding points out that COVID-19 infection might precipitate DKA. Our finding was similar to the finding observed at Jacobi Medical Center, an epicenter of the COVID-19 pandemic crisis in NYC, which noticed that a significant number of patients with COVID-19 presented with DKA [17]. Similarly, in a study of case series presented with DKA and COVID-19 infection to King Saud University hospital in Saudi Arabia, it was shown that COVID-19 infection can precipitate DKA [18]. In Singapore, Chee et al. [19] reported a case of DKA precipitated by COVID-19 infection.

The mechanism of how SARS-CoV-2 could lead to DKA is still poorly understood. Several mechanisms have been suggested based on previous findings with SARS-CoV-1 infection. SARS-CoV-2 could affect the pancreatic cells directly, leading to islet cell damage and reduced insulin secretion. On the other hand, SARS-CoV-2 can bind to angiotensin-converting enzyme 2 (ACE2) receptors, which are present in pancreatic beta islets, leading to their downregulation and subsequent increase in angiotensin 2 levels, resulting in beta cell injury by causing vasoconstriction and reduced blood flow, impaired insulin secretion and subsequent hyperglycemic crisis [18, 19]. Moreover, interleukin-6, which is a cytokine released during the hyper-inflammatory state in COVID-19 infection, has also been found to be high in DKA and play a role in stimulating ketogenesis [20]. These postulated mechanisms play a role in precipitating DKA in patients with COVID-19 disease, in addition to increased production of the counterregulatory hormone by stimulating cytokines released during infection [20].

Both COVID-19 and non-COVID-19 patients had a higher HbA1c level (mean: 13.5% vs. 12.8%, respectively). This finding indicates that uncontrolled diabetes mellitus increases the risk of developing DKA, as previously demonstrated in the literature [21].

With regard to DKA severity, we demonstrated that patients with COVID-19 had more severe DKA (63.6% vs. 52.4%) compared to non-COVID-19, but this was not statistically significant (p = 0.37). This result is similar to the finding of a recent retrospective study [22]. The findings in our study regarding COVID-19 severity in relation to DKA severity were variable. Out of the seven cases of severe DKA, two patients were asymptomatic, three had moderate COVID-19 infection, one had severe, and one had critical COVID-19 infection. We did not observe a relationship between DKA severity and COVID-19 severity apart from diabetes as a risk for severe COVID-19 infection. This was consistent with one retrospective study, which showed that diabetes increased the risk of severe COVID-19 infection [23] and similarly was shown in a recent meta-analysis [24]. There are no definite associations between DKA severity and COVID-19 severity reported in the literature. Recent studies have found that excess fluid resuscitation in DKA management increases the risk of pulmonary edema and subsequent ARDS development in COVID-19 infection [25]. This finding could be attributed to the increased level of angiotensin 2 after binding SARS-CoV-2 to the ACE 2 receptor, which enhances pulmonary vascular permeability, leading to parenchymal lung injury [25].

The median length of hospital stay in our study was longer in the COVID-19 patients compared to the non-COVID-19 patients (7 days vs. 4 days), but this was not statistically significant (p = 0.278). The increased length of hospital stay has been attributed to several factors: COVID-19 infection and its associated complications of pneumonia, renal impairment, and ARDS requiring intubation and ICU admission. All of these conditions require more aggressive treatment and close hospital monitoring, and hence an extended hospitalization. Furthermore, both diabetes and ketosis in patients with COVID-19 infection increase the length of the hospital stay [26].

Interestingly, we observed in our study that the median duration of DKA in the COVID-19 patients was shorter (16 h) than in the non-COVID-19 patients (24 h) (p = 0.043). The patients in both groups of our study received the same management of DKA as per the hospital DKA protocol. However, there was no clear explanation for the above observation. Our finding is in contrast to a study that reported a prolonged duration of DKA for up to 35 h in COVID-19 patients [27]. In another study, the duration of DKA was short (15–17 h) but did not demonstrate any difference between COVID-19 and non-COVID-19 groups [28]. The variations in the results between our study and other studies could be due to the differences in the sample size, the characteristics of the comparator groups, and the DKA management protocols in different hospitals. Further studies with a large sample size are required to assess the duration of DKA and factors affecting it in COVID-19 patients.

Our study found two deaths in the COVID-19 positive group but none in the COVID-19 negative group (p = 0.047). Several meta-analyses showed that diabetes increased the mortality of patients with COVID-19 [24, 29]. The clinical outcome of COVID-19 patients with DKA has been conflicting and variable between the studies. Our finding is consistent with other studies that have reported a high mortality rate in patients with DKA and COVID-19 [17, 30] but contrasts with a study that showed DKA patients were more likely to survive than non-DKA patients [31]. Our study revealed that deceased DKA COVID-19 patients had severe and critical COVID-19 infection, severe DKA, a high CRP level, required ICU admission, and mechanical ventilation, all of which indicate poor prognosis in DKA patients with associated COVID-19 infection. A recent retrospective study reported that 95% of DKA COVID-19 patients who required mechanical ventilation died [32]. Another reported studyshowed a mortality of 88% in COVID-19 patients who were intubated [33].

To the best of our knowledge, this is the first study nationally to assess the clinical profile and outcomes of DKA patients with associated COVID-19 infection in comparison to those without COVID-19. However, our study had some limitations due to the small sample size and the fact that data were collected retrospectively and from a single center.

COVID-19 infection can precipitate DKA in patients with either newly diagnosed or preexisting diabetes. Our study showed that DKA patients with COVID-19 infection had a higher mortality rate and a shorter duration of metabolic ketoacidosis in comparison to DKA patients without COVID-19 infection. The 2 deceased patients in the DKA COVID-19 group were those who required ICU admission and mechanical ventilation. They also had high CRP levels and severe to critical COVID-19 infection.

A larger prospective cohort study is recommended to explore the degree of blood glucose control and its impact on the severity of COVID-19 infection, and if any association between DKA severity and COVID-19 severity does exist. In addition, more studies are needed to assess the prognostic factors in DKA patients with COVID-19.

The COVID-19 pandemic continues to pose a significant impact on health care with the worldwide increase in diabetes prevalence. Appropriate preventive strategies and effective use of telemedicine are crucial to detect undiagnosed cases, ensure adequate glycemic control, prevent acute complications of diabetes like DKA, and improve the prognosis of COVID-19 in diabetic people.

We thank all healthcare providers involved in taking care of patients with COVID-19.

The study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The study protocol was approved by DSREC (Dubai Scientific Research Ethics Committee), code number: (DSREC-08/2020_17). All subjects gave their written informed consent to participate in the study.

The authors have no conflicts of interest to declare.

No funding was received for this study.

Hana AlSughaiyer conceptualized the study design, designed the data collection tool, analyzed the data in its entirety, and was involved in data collection and in writing, review, and editing of the manuscript. Abeer AlHaj designed the data collection tool, was involved in review, and editing of the manuscript. Samia Murad was involved in review of the manuscript. All authors reviewed and agreed the final version of the manuscript.

The data that support the findings of this study are not publicly available due to privacy and confidentiality but are available from the corresponding author upon reasonable request.

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