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ORIGINAL ARTICLE
Year : 2022  |  Volume : 15  |  Issue : 8  |  Page : 317-324  

Study of clinical features, laboratory and radiological findings, morbidity, and mortality in COVID-19 patients with controlled and uncontrolled diabetes mellitus


Department of General Medicine, Dr. D Y Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India

Date of Submission16-Sep-2021
Date of Decision06-Feb-2022
Date of Acceptance14-Feb-2022
Date of Web Publication05-Apr-2022

Correspondence Address:
Dr. Pradnya Diggikar
B G Vastu, Flat No 101, Plot No 305, Sector No 28, Pradhikaran, Near Ganganagar Bus Stop, NIGDI, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_753_21

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  Abstract 


Introduction: Coronavirus disease 19 (COVID-19) is a pandemic caused by a novel coronavirus, the Severe Acute Respiratory Syndrome Coronavirus 2. Diabetes and its complications are major causes of morbidity and mortality. Patients with uncontrolled diabetes may be associated with poorer outcomes as compared with patients with good glycemic control. Methodology: A total of 120 patients with type 2 diabetes mellitus with COVID-19 were taken from a tertiary care center in Pune, Maharashtra, and included in the study following their voluntary informed consent. Results: It was observed that patients with poor glycemic control had a greater prevalence of symptoms including fever (64.9% vs 55.4%), cough (51.3% vs 42.2%), and dyspnoea (40.5% vs 27.7%). C-reactive protein (9.40 vs 5.66), D-dimer (668.2 vs 457.9), and ferritin levels (352 vs 238) were observed to be greater in patients with poor glycemic control. Chest X-Ray changes (45.9% vs 17.2%) and CT severity score (9.32 vs 5.79) were significantly greater in patients with poor glycemic control. Patients with poor glycemic control also had an increased incidence of O2 requirement, increased mortality, and a longer duration of hospital stay. Poor glycemic control was also associated with an increased incidence of complications like acute respiratory distress syndrome (35.1% vs 18.0%), sepsis with or without septic shock (18.9% vs 9.6%), acute coronary syndrome (13.5% vs 8.4%), acute kidney injury (18.9% vs 3.6%), acute hepatic injury (13.5% vs 2.4%), and other complications like diabetic ketoacidosis, pulmonary thromboembolism, and cerebrovascular accident (10.8% vs 6.0%).Conclusion: On the basis of our findings, we concluded that patients with poor glycemic control were associated with poorer outcomes and increased complications.

Keywords: Clinical features, COVID-19, diabetes mellitus, morbidity, mortality


How to cite this article:
Gopal P, Diggikar P, Satya Saranya NS. Study of clinical features, laboratory and radiological findings, morbidity, and mortality in COVID-19 patients with controlled and uncontrolled diabetes mellitus. Med J DY Patil Vidyapeeth 2022;15, Suppl S2:317-24

How to cite this URL:
Gopal P, Diggikar P, Satya Saranya NS. Study of clinical features, laboratory and radiological findings, morbidity, and mortality in COVID-19 patients with controlled and uncontrolled diabetes mellitus. Med J DY Patil Vidyapeeth [serial online] 2022 [cited 2023 Jan 31];15, Suppl S2:317-24. Available from: https://www.mjdrdypv.org/text.asp?2022/15/8/317/342629




  Introduction Top


Coronavirus disease 19 (COVID-19) is a pandemic caused by a novel coronavirus, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2). The current outbreak of the novel coronavirus SARS-CoV-2 (coronavirus disease 2019; previously 2019-nCoV), epi-centered in Hubei Province of the People's Republic of China, has rapidly spread to many other countries. On 30th January 2020, the World health organization Emergency Committee declared a global health emergency based on growing case notification rates at Chinese and international locations.[1]

Coronaviruses are enveloped, positive-sense, single-stranded RNA viruses of ~30 kb. They infect a wide variety of host species. They are largely divided into four genera; α, β, γ, and δ based on their genomic structure. α and β coronaviruses infect only mammals. Human coronaviruses such as 229E and NL63 are responsible for common cold and croup and belong to αcoronaviruses. In contrast, SARS-CoV, Middle East respiratory syndrome coronavirus, and SARS-CoV-2 are classified under β coronaviruses.[2]

The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 not only activates antiviral immune responses but can also cause uncontrolled inflammatory responses characterized by marked pro-inflammatory cytokine release in patients with severe COVID-19, leading to lymphopenia, lymphocyte dysfunction, granulocyte, and monocyte abnormalities. These SARS-CoV-2-induced immune abnormalities may lead to infections by microorganisms, septic shock, and severe multiple organ dysfunction. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 must be elucidated to guide clinical management of the disease. Moreover, rational management of the immune responses to SARS-CoV-2, which includes enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful management.[3]

Current evidence indicates an initial animal-to-human transmission from wild animals traded at the Huanan seafood market in Wuhan. The origin and mechanism of which remain to be clarified—while some genomic studies suggested bats as the natural reservoir,[4] others suggested pangolins.[5] As the outbreak progressed, person-to-person transmission remains the main mode of spread. This is through

  1. Respiratory droplets released via coughing or sneezing,
  2. Aerosol, typically during aerosol-generating clinical procedures, and
  3. Mucosal membrane contact with fomites.[6],[7]


Fecal-oral transmission has been speculated,[8] given the detection of viral RNA in stools, reported gastrointestinal (GI) symptoms, and angiotensin converting enzyme 2 (ACE2) receptor expression along the GI-tract.[9] No evidence of intrauterine or transplacental transmission has been reported.

To date, the RNA virus has caused the death of over 5,325,880 people with over 270,786,885 people infected worldwide. Patients may be asymptomatic, present with mild symptoms like fever and cough, or may present with severe pneumonia associated with acute respiratory failure.

SARS-CoV-2 virus primarily affects the respiratory system, although other organ systems are also involved. Lower respiratory tract infection related symptoms including fever, dry cough, and dyspnoea were reported in the initial case series from Wuhan, China. In addition, headache, dizziness, generalized weakness, vomiting, and diarrhea were observed. It is now widely recognized that respiratory symptoms of COVID-19 are extremely heterogeneous, ranging from minimal symptoms to significant hypoxia with acute respiratory distress syndrome (ARDS).[3]

A large number of patients may be asymptomatic. COVID-19 could be associated with fatal complications such as pneumonia, sepsis, septic shock, ARDS, multi-organ failure, and disseminated intravascular coagulation ultimately leading to death. A high percentage of patients have pre-existing comorbidities including hypertension (HTN), Type 2 Diabetes mellitus (T2DM), obesity, chronic kidney disease (CKD), cardiovascular disease (CVD), old age, and dyslipidemia.

DM is a group of chronic metabolic conditions, all of which are characterized by an elevated blood glucose levels resulting from the body's inability to produce insulin or resistance to insulin action, or both. The disease burden related to DM is rising in every country. The latest estimates show a global prevalence of 382 million people with diabetes in 2013, expected to rise to 595 million by 2035. Diabetes and its complications are major causes of morbidity and mortality and contribute substantially to health care costs. Although studies have failed to show an increased incidence of COVID-19 among diabetic patients, there is evidence to show that diabetic patients with COVID-19 have poor prognosis, severe symptoms, and a higher death rate as compared with non-diabetic patients with similar demographics.

Patients with diabetes have high rates of other metabolic risk factors including HTN, higher body mass index, higher frequency of CKD, coronary artery disease, and heart failure. They also tend to have higher inflammatory markers compared with those without diabetes. There is a lot of literature that has shown the chronic inflammatory state in patients with diabetes. Pro-inflammatory cytokines and increased production of glycosylation end products can all be induced by hyperglycemia and insulin-resistant states. Patients with diabetes have a higher propensity of developing infections, and this chronic inflammatory process may be the underlying mechanism.[10]

Some studies have shown that severe COVID-19 patients have a higher incidence of diabetes than non-severe COVID-19 patients (13.8%–40.0% vs 3.5%–11.0%). Moreover, the proportion of diabetic patients was higher among deceased patients than those who survived.[11] Patients with DM appear to be at a greater risk for severe symptoms and complications, including death from COVID-19.[12],[13] DM is a common comorbidity in patients affected with COVID-19 and may cause ketosis, ketoacidosis, and diabetic ketoacidosis (DKA).[14] A study with more than 1.3 million participants showed that 98% of adults with type 2 diabetes have at least one comorbid chronic disease and almost 90% have at least two.[15],[16] The most commonly associated comorbid conditions in patients with T2DM include HTN (82.1%), overweight/obesity (78.2%), hyperlipidaemia (77.2%), CKD (24.1%), and CVD (21.6%).


  Methods and Materials Top


The total period of study was spread over 3 months from 1st October 2020 to 31st December 2020. Overall 120 patients with T2DM with COVID-19 taken from COVID-19 wards and COVID-19 Intensive care unit (ICU) from a tertiary care center in Pune, Maharashtra, were included in the study following their voluntary informed consent. Ethical clearance for the study was taken from the institutional ethical committee. Data entry was done in MS Excel data sheet. Based on the glycemic control at admission, all patients were categorized into two separate groups. HBA1c of 8 gm% or higher was categorized as group 1 and HBA1c of less than 8 gm% was categorized as group 2.

Data collection

COVID-19 cases were diagnosed by a positive RT-PCR assay of swab specimens taken from the nasopharynx and oropharynx. Data on patients of T2DM, after exclusion of other comorbidities like HTN, ischemic heart disease, chronic pulmonary disease, CKD, chronic liver disease, and cerebrovascular accident were collected and patients were divided into two groups based on their HBA1c levels. Data regarding medical history, clinical features, laboratory investigations, chest X-ray (CXR) findings, high resolution computerised tomography (HRCT) severity score, complications, treatment, and outcome were collected. Data on laboratory investigations included hemogram, C-reactive protein (CRP), ferritin, and D-dimer. The data of patients with complications were collected. Outcome of COVID-19-infected patients was measured by the duration of hospital stay, number of recovered patients, and the total number of deaths. The collected data were compiled, tabulated, analyzed, and correlated to establish differences in COVID-19 manifestations on the basis of glycemic variations in T2DM.

Inclusion criteria

Patients with COVID-19 (RT-PCR positive) in the last 14 days with a history of DM.

Exclusion criteria

Patients with comorbidities like HTN, ischemic heart disease, chronic pulmonary disease, CKD, chronic liver disease, and cerebrovascular accident.

Patients with anaemia

Patients previously on steroids or drugs causing hyperglycemia.


  Results Top


In this study, it was observed that 37 (30.83%) patients had HbA1c level more than 8% and belonged to group 1, whereas 83 (69.17%) patients had HbA1c level less than 8% and belonged to group 2. The mean age of COVID-19 patients with T2DM was 57.56 years (95% CI: 57.56 ± 1.445, SD = 8.07). Mean age of uncontrolled diabetes group was 56.97 years (95% CI: 56.97 ± 2.74, SD = 8.51), whereas mean age in controlled diabetes group was 57.82 years (95% CI: 57.82 ± 1.69, SD = 7.86). The total male patients were 19 in the uncontrolled diabetes group and 39 in the controlled group. The female patients were 18 in the controlled diabetes group and 44 in the uncontrolled group.

Clinical presentation

Most of the COVID-19 patients with T2DM presented with fever (58.3%), cough (45.0%), dyspnea (11.25%), and fatigue (20.0%). A few patients also reported myalgia (10.8%), diarrhea (8.3%), vomiting (5.8%), headache (7.5%), and other symptoms (5.8%) like pain abdomen and altered sensorium.

Fever (64.9% in group 1 vs 55.4% in group 2), cough (51.3% in group 1 vs 42.2% in group 2), and dyspnea (40.5% in group 1 vs 27.7% in group 2) were found more in the uncontrolled diabetes group as compared with the controlled diabetes group [Table 1].
Table 1: Demographics and clinical presentation

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Laboratory and radiological findings

On admission, HBA1c (mean) in the uncontrolled diabetes group was 10.8% as compared with 6.97% in the controlled diabetes group. Fasting sugar levels (BSL-F) on admission in the uncontrolled group was 282.2 mg/dl as compared with 160.6 mg/dl in the controlled diabetes group while the mean total was 198.1 mg/dl.

The hemogram of both the groups showed an average total leukocyte count (TLC) of 7.41 × 109/L and a platelet count of 2.43 Lac/μl. However, patients in uncontrolled diabetes group showed higher TLC counts (7.84 × 109/L) as compared with controlled group (7.21 × 109/L).

The other laboratory investigations were significantly different among the two groups of patients. CRP (9.40 vs 5.66), D-dimer (668.2 vs 457.9), and ferritin levels (352 vs 238) were observed to be greater in group 1 patients in comparison with group 2 patients.

CXR represented classic changes for COVID-19 in 32 patients (26.6%). The average CT severity score was 6.88 out of 25. CXR changes were significantly higher in group 1 (45.9%) than group 2 (18.07%). CT severity score was significantly greater in group 1 (9.32) as compared with group 2 (5.79) [Table 2].
Table 2: Laboratory and radiological findings

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Complications

Totally 28 patients developed ARDS, 15 patients developed sepsis with or without septic shock, 12 patients developed acute cardiac injury, 10 patients developed acute kidney injury, 7 patients developed acute hepatic injury, and 9 patients developed other complications like allergic reactions and DKA.

Complications like ARDS (35.1% vs 18.0%), sepsis with or without septic shock (18.9% vs 9.6%), acute coronary syndrome (13.5% vs 8.4%), acute kidney injury (18.9% vs 3.6%), acute hepatic injury (13.5% vs 2.4%), and other complications like DKA, pulmonary thromboembolism, and CVA (10.8% vs 6.0%) were observed more in patients of uncontrolled diabetes group than in patients of the controlled diabetes group [Table 3].
Table 3: Complications

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Management and outcomes

Requirement of oxygen (O2) supplementation (56.7% vs 30.1%) and non-invasive ventilation (37.8% vs 20.5%) was more in the uncontrolled diabetes group as compared with the controlled diabetes group. A higher number of group 1 patients (27.0%) required invasive ventilation as compared with group 2 patients (15.7%) [Table 4].
Table 4: Need for O2 support, non-invasive, and invasive ventilation

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Out of 120 patients; 95 patients (79.2%) recovered, whereas 25 patients (20.8%) succumbed to COVID-19 [Table 5]. Average duration of hospital stay was more in group 1 patients (15.1 days) as compared with group 2 patients (13.5 days) [Figure 1]. From the above data, we can elicit that the percentage of patients who recovered were lower in group 1 (73%) compared with group 2 (81.9%). COVID-19-related mortality was higher in group 1 compared with group 2 (27.0% vs 18.1%) [Figure 2] and [Figure 3].
Figure 1: Mean duration of hospital stay

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Figure 2: Outcome in group 1

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Figure 3: Outcome in group 2

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Table 5: Outcomes

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  Discussion Top


Mean age of the study population was 57.56 (±1.445) years. The percentage of males (48.3%) and females (51.7%) in our study were almost equal. This was comparable to a study conducted by Abdullah M. Alguwaihes et al.[17] with 439 study participants, where the median age was 55 years. However, the male to female ratio was 2:1 which differed from our study. In another study by Ciardullo S. et al.,[18] which included 373 participants, the mean age was 72 (±14) years with 65.4% males and 34.6% females. This difference may be due to small sample size or due to a difference in local demographics.

Most common clinical feature on presentation was fever (58.3%) followed by cough (45.0%), fatigue (20.0%), and dyspnea (11.25%). In a study by Abdullah M. Alguwaihes et al.,[17] the presenting complaints were fever (75.2%) and cough (70%) and one in every five patients also had vomiting (23.1%) and diarrhea (21.3%). In another study by Ciardullo S. et al.,[18] 82.6% had fever and 39.1% had cough on presentation. This difference may be due to the small sample size of our study. In our study, the clinical features on admission were more pronounced in uncontrolled diabetes group as compared with controlled diabetes group. Fever, cough, and dyspnoea were more common in patients with poor glycemic control, and the underlying cause for such presentation might be early and extensive lung involvement in COVID-19 infection due to greater glycemic variation.

A study by Pawan K. Garg et al.[19] showed a TLC count of 9.19 × 109/L in COVID-19 patients. In our study, the average TLC was 7.41 × 109/L. This difference may be due to small sample size or due to a difference in local demographics. However, in our study, patients in uncontrolled diabetes group showed higher TLC counts (7.84 × 109/L) as compared with controlled diabetes group (7.21 × 109/L). This may be due to the increased incidence of secondary infections more common in patients with uncontrolled diabetes.

A study by Wei Chen et al.[20] showed that plasma CRP levels had a positive correlation with the severity of COVID-19 infection and higher CRP levels were associated with a longer duration of hospital stay. A study by Tobias Herold et al.[21] concluded that CRP levels were highly predictive of the need for mechanical ventilation. In our study, CRP levels were significantly higher in uncontrolled diabetes group CRP (9.40 mg/L) as compared with controlled diabetes group CRP (5.66 mg/L).

A systematic review by Mehrdad Rostami et al.[22] showed that diabetic individuals with COVID-19 had higher D-dimer levels compared with non-diabetic individuals and were more likely to develop severe illness. In our study, patients with uncontrolled diabetes showed higher D-dimer levels (668.2 mg/dL) compared with the controlled diabetes group (457.9 mg/dL).

A meta-analysis and systemic review by Linlin Cheng et al.[23] showed that COVID-19 patients with diabetes had significantly higher levels of serum ferritin and were associated with poorer outcomes. In our study, patients in the uncontrolled diabetes group had higher ferritin levels (352 μg/L) compared with the controlled diabetes group (238 μg/L).

In our study, inflammatory biomarkers such as D-Dimer, ferritin, and CRP were markedly elevated in the uncontrolled diabetes group as compared with the controlled diabetes group and this correlates with the increased severity and poorer outcomes seen in this group. Increased ferritin levels suggest a higher susceptibility of such patients to develop an inflammatory (cytokine) storm which in turn may be associated with a significant rise in D-dimer levels.

A study by Liqa A. Rousan et al.[24] demonstrated CXR abnormalities in 31% of patients as compared with 26.6% in our study. Another study by Rabab Yasin et al.[25] showed X-ray abnormalities in 77% of patients. This difference may be due to the small sample size of our study.

A study by Bita Abbasi et al.[26] found a significant correlation between CT severity score and the rapidity of decline in the clinical condition of the patient. Another study by Ghufran Aref Saeed et al.[27] showed a significant correlation between DM and CT severity scores and was in turn associated with poorer outcomes. In our study, significantly higher CT severity scores were seen in the uncontrolled diabetes group (9.32) as compared with the controlled diabetes group (5.79). CXR findings and CT severity score indicate extensive lung involvement in patients with uncontrolled diabetes. These radiological findings indicate a more severe pneumonia in patients with poor glycemic control as compared with patients with controlled diabetes.

A study by Susan J. Tzotzos et al.[28] showed that 33% of hospitalized patients developed ARDS and a study by Aibin Wang et al.[29] showed that 20% of COVID-19 patients developed ARDS. In our study, 23.3% of patients developed ARDS but this percentage was significantly higher in the uncontrolled diabetes group (35.1%). Several studies have demonstrated that secondary systemic complications like sepsis with or without septic shock, acute coronary syndrome, acute kidney injury, acute hepatic injury, DKA, pulmonary thromboembolism, and CVA were more common in diabetic patients especially in patients with uncontrolled diabetes as is reflected in our study. This may be due to the increased inflammatory markers seen in COVID-19 patients with uncontrolled diabetes causing to an inflammatory response with cytokine storm leading to multisystem involvement.

A study by Jacqueline Seiglie et al.[30] demonstrated that patients with uncontrolled DM were at a significantly higher risk for ICU admission, increased duration of ICU stay, and the need for oxygen supplementation and mechanical ventilation. It also showed a significantly higher mortality in patients with uncontrolled DM as compared with patients with good glycemic control. This is comparable to our study which shows a significantly higher need for oxygen supplementation and mechanical ventilation in patients with uncontrolled DM. Our study also shows an increased duration of hospital stay as well as increased mortality in patients with uncontrolled DM.


  Conclusion Top


From our study, it can be concluded that patients with uncontrolled DM are at a greater risk of developing a severe and fatal COVID-19 infection. The severity of COVID-19 in diabetics could be attributable to the dysfunctional immune system. Uncontrolled diabetics also have a greater susceptibility to viral infections and an exaggerated immune response. COVID-19 patients with uncontrolled diabetes require greater care in terms of medical and supportive therapy than those with controlled diabetes group. Patients with uncontrolled diabetes have a greater symptomatic presentation, rapid pulmonary invasion, and a greater requirement of intensive care. They are at a greater risk for severe illness and poorer outcomes. Hence, extreme care should be taken in prevention and management of COVID-19 infection in patients with underlying DM.

Ethics committee approval

Ethical clearance number: I.E.S.C/51/2021.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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