**1. Introduction**

The available data so far indicatethat in SARS-CoV-2, the nature of the pathology goes beyond acute respiratory infection [1–4]. Researchers identify 2 more disease periods associated with SARS-coronavirus-2 infection, including a rare hyperinflammatory syndrome after an acute period and late inflammatory andvirological complications [1, 2]. These 3 disease periods not only determine the time course of SARS-CoV-2 infection at the population level, but also reflect the possible multiple organ involvement [1, 2, 5]. Patients may have pronounced cardiovascular and gastrointestinal lesions, and dermatological and cutaneous-mucous manifestations, such as giperosmolarna with Kawasaki disease [1, 2]. Laboratory studies can reveal elevated inflammatory markers (e.g., levels of C-reactive protein and ferritin), a coagulopathy (e.g. D-dimer) and elevated cardiac markers (troponin level), [6, 7]. According to the available data and according to some experts, the COVID-19 developing trebovatelna process or COVID-19-associated coagulopathy [5, 8, 9].

To the development of the disease most often predispose:


According to sources from the Chinese center for disease control and prevention (February 2020) and who information materials [12, 13], the death rate from COVID-19 largely depends on the age of patients and the presence of chronic diseases, including diabetes mellitus (**Figure 1**). Based on the study of 72,314 cases of COVID-19, the researchers obtained the following statistics: patients suffering from cardiovascular diseases had a mortality rate of 13.2%, with verified diabetes mellitus 9.2%, with arterial hypertension 8.4%, with chronic forms of diseases respiratory tract 8%, with oncological pathology 7.6% [12, 13].

*Frequency of Hyperglycemia in Patients with Covid-19 Infection and Pneumonia DOI: http://dx.doi.org/10.5772/intechopen.96306*

#### **Figure 1.**

*Mortality rate of covid-19 patients by chronic disease (sources: WHO, Chinese authorities as of February 2020), [12, 13].*

Diabetes can increase the risk of death in COVID-19 by 12 times, according to the portal of the US Centers for disease control and prevention [14]. Coronavirusinfected diabetics are six times more likely to need hospital admission and inpatient treatment, and diabetes is the second most severe complication in COVID-19 after cardiovascular disease [15].

The state of carbohydrate metabolism in patients with COVID-19 has not been sufficiently studied in clinical studies. Isolated studies indicate that viral infection may be accompanied by an increase in the concentration of glycated hemoglobin in patients with viral pneumonia [16–18].

#### **2. Purpose and objectives of the study**

To assess the frequency of fasting hyperglycemia and the frequency of diagnosis of newly diagnosed diabetes mellitus in patients with COVID-19 and acute lung damage aged 41–80 years, who were hospitalized in a repurposed infectious diseases hospital in Moscow with a diagnosis of pneumonia.

#### **3. Material and methods**

We have analyzed laboratory and clinical diagnostic data of 278 patients who had, according to the anamnesis and the medical conclusions of impaired glucose tolerance and manifested forms of diabetes, including 163 men and 115 women, aged 41–80 years, admitted to the hospital for diagnosis and treatment in the period from 12.04.2020 on 10.11.2020 of diagnoses according to international classification of diseases and causes of death revision 10 (ICD-10): U07.1 Coronavirus infection caused by a virus COVID-19, virus identified (confirmed by laboratory testing regardless of the severity of clinical signs or symptoms); J12.9 community acquired pneumonia. Patients 'data were archived in the city computer system of DZM KIS EMIAS (unified medical information and analytical system Department of health

of the city of Moscow). All patients were admitted to the hospital with fever symptoms, cough complaints, and shortness of breath. After inpatient treatment, all patients showed regression of inflammatory changes in the lungs and improvement of their condition. Patients were divided into groups depending on their age and the results of biochemical (PCR diagnostics and enzyme immunoassay for determining the concentration of M and G-immunoglobulins) and clinical-radiological studies


#### **Table 1.**

*The nature of the respiratory system pathology and the frequency of respiratory failure in two groups of patients without clinical, radiological and biochemical signs of COVID-19.*

#### *Frequency of Hyperglycemia in Patients with Covid-19 Infection and Pneumonia DOI: http://dx.doi.org/10.5772/intechopen.96306*

MSCT (multispiral computed tomography of the chest and lung radiography) performed in all 278 patients. Diagnosis COVID-19 was verified from 162 patients, including 86 men and 76 women who were divided into two groups according to age: 1st - 86 patients at the age from 41 to 60 years, an average of 50.7 ± 1.8 years, men 50(58.1 per cent), women 36(41.9 percent) and 3-group, 76 patients aged 61 to 80 years, an average of 70.3 ± 2.6 years, men 36,women 40. The comparison group consisted of 116 patients, including 77 men and 39 women with pathology of respiratory system coming to the hospital on an emergency basis with referral physician diagnosis of SMP J12.9 community acquired pneumonia, in which the results of the study in the hospital signs of infection COVID-19 have been identified. By age, these patients were divided into two groups: group 2–57 patients aged 41–60 years, average 50.2 ± 2.4, men 36, women 21 and group 4–59 patients, including 41 men and 18 women, age from 61 to 80 years, average age 66.3 ± 1.5 years. The nature of the pathology of the lungs and respiratory system in patients without signs of covid-19 infection is shown in **Table 1**.

The nature of lung damage according to the chest MSCT method and the severity of respiratory failure in patients with COVID-19 and pneumonia are shown in **Table 2**.

In the selected groups of patients, theinitial and subsequent fasting blood glucose levels were analyzed after 8 hours without food intake on a stationary automatic analyzer and using portable glucose, meters using diagnostic test strips. The concentration of glucose and ketones in the urine was determined by a semiquantitative method. We evaluated the dynamics of indicators when detecting pathological values of glucose concentration. Glucose levels above 6.4 mmol/l were taken as pathological.


*Note: MSCT scan 0 Lungs are clean, there are no lesions. CT1 Focal inflammatory processes filling no more than 25% of alveoli. CT2 Half of the lung tissue is affected. CT3 Up to 75% of lungs are involved in the pathological process. CT4 Bilateral interstitial pneumonia, complete filling of the lung tissue with exudate. The condition is designated by the term respiratory distress syndrome, requires connection to a ventilator. From the site: https://tyubik.net/lecheniyepreparatami/991-kt-1-2-3-4-chto-jeto-znachit-pri-koronaviruse .html.*

**Table 2.**

*The frequency of detection of pneumonia in one and two lungs, the severity of pneumonia according to the criteria of multispiral computed tomography of the lungs, and the severity of respiratory failure in two groups of patients of different ages with COVID-19 (number of cases, frequency in %).*

To assess hyperglycemia and diabetes, the "criteria for newly diagnosed diabetes mellitus" were used [World Health Organization, WHO, 9 June 2012]:


If there are no symptoms of diabetes, a second test should be performed on a different day to confirm the diagnosis. If the diagnosis cannot be confirmed by the level of fasting glycemia or by random measurement, a glucose tolerance test is performed.

**Note:** The normal concentration of fasting plasma glucose is considered to be 6.1 mmol/l. Impaired glucose tolerance is diagnosed when the fasting plasma glucose concentration is 6.1–7.0 mmol/l. A preliminary diagnosis of diabetes mellitus is established at an fasting plasma glucose concentration of 7.0 mmol/l. The diagnosis of diabetes must be confirmed.

At values above 7.0 mmol/l, according to WHO recommendations, 2012, a glucose tolerance test was performed and the level of glycosylated hemoglobin in the patient's peripheral blood was determined. The level of triglycerides and cholesterol in the blood serum was determined using a Getpremier spectrophotometer (USA). The level of pathologically elevated triglyceride concentrations was considered to be values above 2.8 mmol/l, cholesterol concentrations above 5.2 mmol/l.

Exclusion criteria. The sample did not include patients with worsening of pneumonia, transfer to the intensive care unit, death due to complications of covid infection, cirrhosis of the liver, oncopathology and hemoblastosis, chronic kidney disease of stages 4 and 5, purulent lung lesions, heart failure above stage 2A, with previously diagnosed diabetes and glucose tolerance disorders.

Methods of statistical processing of the obtained data. All the results of the study were processed statistically using the Exsel and Statgraphics software packages (version 2.6). The student's "t-test" was used to compare continuous variables. The Chi – square test or Fisher's exact test were used to evaluate a feature that characterizes the frequency of the phenomenon. The values were compared with the non-Gaussian distribution using the Mann–Whitney U-test. The average intergroup differences of the same type of indicators were compared with the assessment of the reliability of the detected differences.Were considered to be reliable values at p < 0,05.

### **4. Results and discussion**

The detection rate of hyperglycemia exceeded 30% in group 1 of patients aged 41–60 years with COVID-19 and pneumonia, hyperglycemia persisted during the hospital follow - up period – in 14%, and the frequency of newly diagnosed diabetes mellitus exceeded 9% (**Table 3**). For all these parameters, we did not find any


*Frequency of Hyperglycemia in Patients with Covid-19 Infection and Pneumonia DOI: http://dx.doi.org/10.5772/intechopen.96306*

#### **Table 3.**

*Frequency of diagnosis of hyperglycemia, glucosuria, ketonuria and newly diagnosed diabetes mellitus in groups of patients aged 41–60 years with COVID-19 and pneumonia (group 1) and in patients with respiratory system damage without COVID-19 infection (group 2).*

significant differences from the average values in the 2nd comparison group.The frequency of diagnosis of ketonuria in urine was 3.6 times higher in group 1 (the difference was statistically significant, p).

In the study of lipid metabolism in groups of patients it was found that pukazatel the frequency of hypertriglyceridemia was 25% in the 1st group of patients and was significantly higher than the values of the comparison group - 2-group, in which cases the improvement in the levels of TG in peripheral blood have been identified (**Table 4**). The average values of the concentrations of this lipid was also significantly higher in patients with COVID-19 and pneumonia (group 1), by 43.4% (p < 0,001). The frequency of hypercholesterolemia was higher in the 1st group of patients – in 22.2% of patients and exceeded by 18.4% (significantly, p).

The frequency of hyperglycemia detection exceeded 45% in group 3 patients aged 61–80 years with COVID-19 and pneumonia, hyperglycemia persisted during the hospital follow - up period – in 16.7%, and the frequency of newly diagnosed diabetes mellitus exceeded 13% (**Table 5**). In these parameters, except for the frequency of hyperglycemia preservation, we did not detect significant differences from the average values in group 4 comparison.

This indicator was 20.4% higher in the 1st group of patients, the difference was significant (p < 0.05). The frequency of diagnosis of ketonuria in urine was 2.0 times higher in group 1 (the difference is statistically unreliable, p > 0.2), but the average concentration of ketone bodies was 47.9% lower (significantly, p < 0,001).

We did not detect any cases of pathological elevation of TG levels in peripheral blood in groups 3 and 4 of patients (**Table 6**). The Mean values of the concentration of this lipid also did not differ significantly and significantly in patients with COVID-19 and pneumonia (group 3), and in patients of the comparison group (group 4). The frequency of hypercholesterolemia was also higher in the 4th group of patients – in 23.6% of patients and exceeded by 14.7% (unreliable, p > 0,05).

To clarify the nature of the association of hyperglycemia with comorbidity and the nature of therapy in patients with COVID-19 and pneumonia, we compared the


#### **Table 4.**

*The nature of changes in the concentration of triglycerides and cholesterol in peripheral blood in patients aged 41–60 years with COVID-19 and pneumonia (group 1) and in patients with respiratory system damage without COVID-19 infection (group 2), M ± m, the frequency of the sign in % and the significance of differences.*


*Frequency of Hyperglycemia in Patients with Covid-19 Infection and Pneumonia DOI: http://dx.doi.org/10.5772/intechopen.96306*

#### **Table 5.**

*Frequency of diagnosis of hyperglycemia, glucosuria, ketonuria and newly diagnosed diabetes mellitus in groups of patients aged 61–80 years with COVID-19 and pneumonia (group 3) and in patients with respiratory system damage without COVID-19 infection (group 4).*

frequency of diseases recorded in medical records in 162 patients aged 41–80 years, including 63 with hyperglycemia and 99 with normoglycemia (**Table 7**). A statistically significant association with hyperglycemia was confirmed only for the diagnosis of grade 2–3 hypertension (arterial hypertension) – the difference between the groups was 22.8% (p < 0,03). The sign of grade 2–3 obesity was 16.8% more common in patients with hyperglycemia, the difference is on the verge of statistical significance (p > 0.05).

The study conducted in patients aged 41–80 years admitted to the hospital with suspected covid-19 infection revealed fasting hyperglycemia in 31–47% of different age groups, and newly diagnosed DM in 9–13% of patients. Comparison with groups of patients with acute and chronic lung pathology did not allow us to note significant and significant differences in these indicators. These data suggest that the development of covid infection with the addition of pneumonia is a significant factor in both the development of transient hyperglycemia and the manifestation of diabetes mellitus.


#### **Table 6.**

*The nature of changes in the concentration of triglycerides (TG) and cholesterol (CH) in peripheral blood in patients aged 61–80 years with COVID-19 and pneumonia (group 3) and in patients with respiratory system damage without COVID-19 infection (group 4), M ± m, the frequency of the sign in % and the significance of differences.*


#### **Table 7.**

*The degree of difference in the frequency of certain forms of pathology and treatment measures in patients with COVID-19 and pneumonia aged 41–80 years, which prevailed in patients with hyperglycemia (n = 63), compared with patients with normal blood glucose concentration (n = 99).*

Our data are confirmed by the results obtained in previous studies on the clinical assessment of the course of covid-19 in patients at a hospital in Wuhan (China). Thus, the authors reported that of 99 infected individuals, it was shown that 52% had elevated glucose levels, and in some patients with viral pneumonia, virus infection was accompanied by an increase in the concentration of glycated hemoglobin [19].

#### *Frequency of Hyperglycemia in Patients with Covid-19 Infection and Pneumonia DOI: http://dx.doi.org/10.5772/intechopen.96306*

According to our data, in 16.6–31.3% of patients after treatment and regression of changes in the lungs, normalization of glucose levels was also observed, but in 14.8–16.7% the changes persisted, and in 9–13% of them, after an additional study, newly diagnosed diabetes mellitus was diagnosed. From these data, it can be assumed that the effect of covid-viral infection on carbohydrate metabolism in patients with pneumonia is observed mainly in the acute period of the disease, but in some patients, the disease in subsequent periods may manifest previously existing prerequisites for the development of chronic pathology (diabetes mellitus).

A feature of carbohydrate metabolism disorders in patients with COVID-19 and pneumonia in our study was a high frequency of ketonuria – more than 45% of patients aged 41–60 years studied in group 1. In the 3rd group of older patients, this pattern was less pronounced, the frequency of ketonuria exceeded 20%. We tried to link this feature of changes in the metabolism of ketone bodies with the vastness of the lung lesion and impaired gas exchange. However, a comparison of the rates of respiratory failure of varying severity in groups 1–3 of patients with COVID-19, as well as indicators of the severity of lung damage according to the diagnostic criteria of the chest MSCT method (multispiral computed tomography of the chest), did not reveal significant and significant differences between the groups. Based on the obtained data, we suggested that viral antigens can change the parameters of tissue membrane permeability for glucose in patients, with an increase in under-oxidized ketone bodies in the bloodstream and an increase in their urinary excretion. The rate of elimination of ketone bodies in the urine was apparently, higher in patients with COVID-19 in group 1 aged 41–60 years than in group 3, 61–80 years, which can be explained by a more preserved filtration function of the kidneys in the younger part of patients with this infection.

To date, apparently, only a few studies have estimated the prevalence of acidosis and ketoacidosis in a large number (n = 658) hospitalized patients with confirmed COVID-19 [20]. Of this sample, 42 (6.4%) patients had positive urine or serum ketones, with only three of 42 (7%) meeting the American Diabetes Association criteria for decompensated ketoacidosis (DKA). People with ketosis were about twice as likely to develop diabetes in this study, and three people who developed DKA were diagnosed with diabetes [20]. In a review and analytical article by employees from the Italian University and the Nephrological Center of Naples (Campania University, "Luigi Vanvitelli", and Nefrocenter Research & Nyx Start-UP, Naples, Italy), the nature of keto-acidotic conditions in patients with COVID-19 is analyzed The authors believe that at the onset of diabetes such conditions may include the socalled pre-diabetic state (impaired fasting glucose and impaired glucose tolerance), which occur with persistently normal levels of glycated hemoglobin, in addition, with a temporary hyperglycemic effect, usually observed in any acute or severe inflammatory disease, or symptoms and signs of ketoacidosis in patients, causes decompensated diabetes [21]. In actual clinical practice, clinicians may classify any event that occurs in people with high blood sugar levels as decompensated ketoacidosis (DKA), regardless of whether it was a real case of DKA or the accumulation of ketones was a consequence of respiratory acidosis potentiated by malnutrition (ion-controlled ketosis). A factor of keto-acidosis can also be a high concentration of inflammatory markers in the blood of patients with COVID-19, which is also typical for DKA, regardless of the concomitant disease [22, 23].

This assumption is confirmed by the results of studies in groups of patients with COVID-19 indicators of lipid metabolism. Since the natural type of lipid changes in diabetes mellitus, according to the literature, hypercholesterolemia are the most common types of lipid changes in diabetes mellitus, we analyzed these lipid parameters. The frequency of both hypertriglyceridemia and hypercholesterolemia in the

group of patients aged 41–60 years with COVID-19 and pneumonia exceeded 22% and was significantly higher than in the comparison group of patients of similar age without this viral infection. However, we did not find such differences in the groups of older patients. These data allowed us to assume that COVID-19 infection to a greater extent can affect glucose-dependent mechanisms of lipid exchange of triglycerides and cholesterol in patients with pneumonia at the age of 61 years than in older patients in whom lipid changes often cause not acute, and chronic factors associated with age-related changes of liver function and central hemodynamics. To clarify this issue, we analyzed the frequency of diagnosis of various forms of pathology, including cardiovascular, in patients with COVID-19 and pneumonia with hyperglycemia and normoglycemia in the general group of patients aged 41–80 years. The comparison allowed us to establish that hyperglycemia was significantly more often detected in patients with arterial hypertension of 2–3 degrees of severity and-with a tendency to reliability-more often in patients with obesity of 2–3 degrees. Neither coronary atherosclerosis (confirmed by coronary angiography and coronary stenosis plastic surgery), nor the frequency of previously developed cardiosclerosis with damage to the cardiac conduction system and the development of atrial fibrillation, nor liver damage in viral hepatitis and chronic alcoholism in the groups of patients with COVID-19 and pneumonia had a significant direct relationship with the frequency of detected cases of hyperglycemia.
