Молодежный инновационный вестник

2415-7805

Федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный медицинский университет имени Н.Н. Бурденко" Министерства здравоохранения Российской Федерации

8352

Unclassified

DIABETES MELLITUS AND NOVEL CORONAVIRUS INFECTION: FEATURES OF PATHOGENESIS, COURSE AND DIAGNOSTICS

Volynkina

Ekaterina A.

studentVolynkina.k@mail.ruhttps://orcid.org/0009-0005-4006-4177Khodarina

Yulia V.

hodarina@list.ruhttps://orcid.org/0000-0001-6513-7735Makeeva

Anna V.

Ph.D. in biology, Associate Professormakeeva81@mail.ruhttps://orcid.org/0000-0002-4926-167XVolynkina

Anna P.

MD, Associate Professoranna-volynkina@mail.ruhttps://orcid.org/0000-0001-8942-6224

Voronezh State Medical University named after N. N. Burdenko

20042023

12S2642644

14022023

05042023

2023

Relevance. More than 600 million cases of a new coronavirus infection with a mortality rate of about 1% have been registered in the world so far. People with comorbidities, including diabetes mellitus, are more susceptible to the adverse course of COVID-19. Numerous studies confirm that post-COVID syndrome is more often formed in the presence of DM. Objective of the study. To reveal characteristic features of course and diagnostics of new coronavirus infection against the background of concomitant diabetes mellitus taking into consideration pathophysiological ways of mutual influence of these pathologies. Materials and Methods. Questions of course and diagnostics of new coronavirus infection on a background of diabetes mellitus were studied; main pathogenesis ways of this comorbid condition were analyzed, the factors influencing negatively on the patient's state against the background of disease development were revealed. To confirm or refute the hypotheses, data of 154 patients who were treated at the "COVID-8" department of the VCCEH No.10 during the period from October 2020 till March 2021 were collected and analyzed. The data were statistically processed using Microsoft Excel 10.0 and StatSoft STATISTICA 12.0 software packages. Results of the study. Compared with the CORONADO data, obesity was much less common in the present study. Of the comorbidities, hypertension, CHD, and coronary artery disease were identified to the greatest extent. Differences with baseline data were also observed for the main complaints. Patients with diabetes mellitus type 2 are characterized by more severe form of the disease according to many indicators. However, there was no statistical significance in the differences in CT and some laboratory indexes. Conclusion. Understanding of pathophysiological mechanisms of mutual influence of DM and new coronavirus infection will serve as a tool for selection of appropriate drug therapy and help to achieve better treatment results.

COVID-19diabetes mellitusnovel coronavirus infectioncomorbid pathologychronic hyperglycemialeukocyte formula

COVID-19сахарный диабетновая коронавирусная инфекциясопутствующая патологияхроническая гипергликемиялейкоцитарная формула

Relevance. There are currently more than 600 million cases of COVID-19 worldwide, according to the Johns Hopkins University Center for Systems Science and Engineering (data updated daily). This pathology is associated with a large number of deaths - more than 6 million people have already died from a new coronavirus infection. The results of the first wave of the disease show that people with comorbid pathology and metabolic disorders are at risk for severe NCI and adverse outcomes. Diabetes mellitus (DM), the most common endocrine pathology, is initially characterized by severe somatic manifestations. This disease is one of the most significant risk factors for the adverse course of COVID-19 [1]. Numerous studies suggest that people with DM are more prone to the formation of post-COVID syndrome (so-called long-COVID), breakthrough infections and cases of reinfection [2]. Purpose of the study. To reveal characteristic features of the course and diagnosis of new coronavirus infection on the background of concomitant diabetes mellitus, taking into account pathophysiological ways of mutual influence of these pathologies. Material and research methods. Russian and international scientific publications on the topic of comorbid pathology of diabetes mellitus+COVID-19 were analyzed. Based on the results of the studies, hypotheses were formulated regarding the diagnosis and prognostic factors of the course of NCI against the background of concomitant diabetes mellitus. To confirm or refute the hypotheses, data of 154 patients' medical charts were collected and analyzed, who were treated at the "COVID-8" department of the VCCEH №10 during the period from October 2020 till March 2021. The following parameters were assessed: comorbid pathology presence, features of NCI course in the background of DM, data of laboratory and instrumental studies. Statistical data processing was performed using Microsoft Excel 10.0 and StatSoft STATISTICA 12.0 software packages. Results. The first stage of the study was the search and evaluation of existing Russian and international scientific papers on the stated topic with further comparison of the results of publications with the data obtained in the course of this work. Multicenter observational study CORONADO, conducted during the first wave of NCI in France, revealed the peculiarities of patient phenotype characteristic of the described pathologies. According to the study, men (63.7%) were more frequently represented in this group of patients, with a mean age of 69.7 years [3]. These results do not compare with the cohort of patients presented in our study (male to female ratio - 30% and 70% respectively, mean age of patients - 63.2 years). According to CORONADO, about one-third (39%) of patients were obese [3]. In our study, obesity was observed slightly less frequently - in 31.4% of the study subjects. Almost all patients in this group suffer from co-morbidities. In CORONADO, hypertension occurred in 76.8% of cases, heart failure in 11.4%, obstructive sleep apnea syndrome in 10.5%, and chronic obstructive pulmonary disease in 9.6% [3]. The most frequent comorbidities in the present work were hypertension (93% of patients), coronary heart disease (82%), chronic heart failure (81%), cerebrovascular disease (38%), chronic pancreatitis and chronic pyelonephritis (34% each). The most common complaints according to CORONADO results were fever (75.4%) and dyspnea (64.3%) [3]. Gastrointestinal disorders were observed in one third of the patients. In our study, patients complained most often about general weakness (88% of respondents), fever (80%), and shortness of breath (54%). A dry cough was observed in every second patient (51% of those studied), and one-third of patients suffered from chest discomfort (29%). Type 2 DM is regarded as a risk factor for the severe course of coronavirus infection. Many mechanisms have been described to explain the worse prognosis of NCI in people with diabetes, but they still remain only speculation. Among these mechanisms are impaired neutrophil degranulation and complement activation, elevated glucose concentrations in airway secretions that significantly increase viral replication, an excessive proinflammatory cytokine response, reduced virus detection, and most significantly, the presence of comorbid diseases [4]. When comparing the course of coronavirus infection in patients with different metabolic backgrounds, patients with type 2 diabetes tend to develop more severe forms of the disease and show a significant increase in inflammatory markers compared to patients without diabetes (high levels of CRP, procalcitonin, ferritin, LDH and D-dimer) [5]. In this study, all patients were divided into 2 groups depending on the presence or absence of diabetes mellitus in the history: Group 1 - patients with COVID-19 and DM (n=105 people) and Group 2 - patients with NCI without DM (n=49 people). There were no significant differences in the levels of CRP, ferritin, and D-dimer. Mean level of plasma leukocytes and CRP was higher in group 1 compared to group 2, but statistically significant (p0.05) was not revealed. Analysis of laboratory data revealed significantly higher levels of proteinuria in the group of patients with NCI against a background of DM, p=0.005. Probably, these results are a consequence of the development of diabetic nephropathy in group 1 against the background of a long course of diabetes mellitus. Pathogenesis of mutual influence of DM and new coronavirus infection on each other is complex and includes many different mechanisms. The course of diabetes is often accompanied by chronic subclinical and low-symptomatic inflammatory reactions as a manifestation of various late complications of the disease. Chronic inflammation leads to decreased production of anti-inflammatory cytokines and increased production of proinflammatory cytokines, including TNF-a, IL-6 and IL-1B [6]. Infection with SARS-Cov-2 in people with diabetes triggers a cascade of reactions. The proinflammatory cytokines described above suppress insulin receptor signaling, resulting in worsening insulin resistance. Changes in innate and acquired immunity, including an abnormal cytokine response, inhibition of leukocyte recruitment, and neutrophil dysfunction trigger a state of chronic hyperglycemia [6]. Prolonged elevation of blood glucose levels results in excessive glycosylation of proteins, including angiotensin-converting enzyme type 2 (ACE-2). It is well known that the SARS-CoV-2 virus uses ACE-2 to mediate entry into the cell. Thus, excessive glycosylation of ACE-2 increases viral proliferation and aggravates the course of coronavirus infection [6]. The severity of the course of NCI in the present study was assessed by the level of lung lesions on computed tomography (CT) images, the mean SpO2 value without oxygen support, and the number of bed-days spent in hospital. It was found that grade 3 and 4 lung tissue lesions on CT scans were more frequent in group 1 (Fig. 1), but there was no statistical significance (p=0.3). The number of bed-days spent in hospital (b/d) was expectedly greater in the group of patients suffering from DM and NCI (median in group 1 - 12 b/d, in group 2 - 10 b/d), statistical significance was found (p=0.001). The analysis of mean SpO2 level without oxygen support in Group 1 revealed lower values, indicating a more severe course of NCI in patients with concomitant DM, but no statistical significance was determined. In order to assess prognostic levels of laboratory data, correlation relations between SpO2 values without oxygen support and leukocyte formula values, as well as coagulogram and blood biochemical analysis data were studied. A negative correlation was found between the relative number of lymphocytes and blood saturation level (p=-0.03). A positive correlation is determined between plasma oxygenation indices and the relative number of basophilic cells (p=0,02). In biochemical blood analysis, creatinine level was of the greatest interest - it also influenced SpO2 value. A negative correlation between these indices was revealed (p=-0.011). When analyzing the coagulogram data, INR value had a significant influence on blood saturation level - a negative correlation relationship was determined (p=-0,03). Discussion of the results. Severe course of new coronavirus infection against the background of concomitant diabetes mellitus causes pathophysiological mechanisms of mutual influence of diseases on each other. As a result of chronic hyperglycemia in diabetes, excessive glycosylation of proteins develops. The SARS-CoV-2 virus, which uses the ACE type 2 protein to enter the cell, is under favorable conditions for increased viral proliferation when glycemia levels are elevated. This is one of the reasons for a more severe course of NCI in DM. Viral load in type 2 diabetes increases the activity of pro-inflammatory cytokines, which suppresses insulin receptor signaling and exacerbates insulin resistance, which is the pathophysiological basis for the formation and adverse course of diabetes. In NCI there are changes in innate and acquired immunity, including neutrophil dysfunction and abnormal cytokine response. They provoke a state of chronic hyperglycemia. Thus, the "vicious circle" of COVID-19 pathogenesis on the background of concomitant diabetes mellitus is closed. Conclusions. The presence of comorbid pathology is one of the most significant risk factors for the severe course of NCI. Among patients with diabetes mellitus tainted with coronavirus infection every third is obese, which aggravates the course of the acute disease. In addition, the vast majority of patients in this group suffer from episodes of high blood pressure, chest pain, and heart rhythm disturbances. General weakness, hyperthermia and dyspnea were the most frequent complaints of patients with NCI and DM. More severe course of COVID-19 against the background of concomitant diabetes mellitus was noted. This is confirmed by CT scan data and the number of bed-days spent in the hospital. This cohort of patients showed higher levels of blood leukocytes and sedimentation rate. The average SpO2 level, which is one of the indicators of NCI course severity, correlates with the laboratory data. High INR and relative lymphocyte counts, as well as decreased plasma basophil levels were prognostically unfavorable. Thus, type 2 DM influences viral proliferation in COVID-19 and is one of the risk factors for an unfavorable course of this disease. Understanding the interactions between the two pathologies is crucial in choosing appropriate therapeutic approaches.

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