The aim of the study is to identify and evaluate the general immunological reactivity of patients with COVID-19 and its relationship with gene polymorphism, severity of the clinical course of the disease and combination with comorbidities. A cohort study was conducted involving 204 patients with COVID-19 diagnosed with community-acquired pneumonia of mild, moderate, and severe degrees who also had comorbidities: endocrinopathies (46 patients), cardiovascular diseases (82 patients), and comorbidities of the ENT organs, connective tissue, gastrointestinal tract, chronic kidney disease (CKD), which were grouped into the group "other comorbidities (76 patients). Among the patients there were 51.97% (106) women and 48.03% (98) men. The average age of patients was 55.93±8.75 years. The polymorphism of the NOS3 (rs2070744), FGB (rs1800790) and TMPRSS2 (rs12329760) genes was determined by real-time polymerase chain reaction (qualitative determination). The overall immunological reactivity was detected and evaluated based on the analysis of 14 integral leukocyte indices: leukocyte shift index, absolute leukocyte count/erythrocyte sedimentation rate (ESR) ratio index, lymphocyte-granulocyte index, lymphocyte index, immunological resistance and reactivity index, and others. The overall immunological reactivity of the body of patients with coronavirus infection increases in the presence of the wild-type T-allele of the eNOS gene (rs2070744) in the patient's genotype, especially the CC genotype, by 21.98-57.89% (p≤0.029-0.001), against the background of a decrease in the index of nonspecific reactivity and the ratio of agranulocytes to ESR – by 23.0 (p=0.039) and 15.74% (p=0.044), indicating the onset of specific immunological reactions in the active infectious process. Carriers of the mutational A-allele of the FGB gene (rs1800790) and the TT genotype of the TMPRSS2 gene (rs12329760) showed higher immune reactivity and resistance, which was significantly confirmed by the level of increase in immune reactivity by 6.31-17.21% (p=0.007) and 22.05-35.78% (p≤0.06-0.004), respectively, against the background of a slightly higher rate of allergy (especially in owners of the AG genotype of the FGB gene – by 68.18%, PAG=0.017), a higher ratio of agranulocytes and ESR – by 18.30-21.84% (p≤0.008-0.007) and 19.46-31.07% (p=0.023), with a higher ratio of lymphocytes and eosinophils – by 13.35-19.20% (p≤0.002-0.001). The influence of the wild-type T-allele of the eNOS gene (rs2070744), the A-allele of the FGB gene (rs1800790) and the TT genotype of the TMPRSS2 gene (rs12329760) on the immunological reactivity of the body of a patient with coronavirus infection was revealed.

The purpose of this study was to investigate polymorphic variants of the genes FGB (rs1800790), NOS3 (rs2070744) and TMPRSS2 (rs12329760) in patients with SARS-CoV-2 and to determine their role in the COVID-19 severity course against the background of antiviral therapy. Real-time polymerase chain reaction (RT-PCR) was used to genotype the polymorphism of the selected genes. GS-5734 (remdesivir) was prescribed as the basic antiviral drug. Binary logistic regression confirmed a low probability of COVID-19 developing in carriers of the A-allele of the FGB gene. The highest probability of moderate and severe COVID-19 clinical forms developing was found in G-allele carriers (especially the GG genotype) of the FGB gene (rs1800790) and the T-allele of the TMPRSS2 gene (rs12329760). Antiviral drug GS-5734 (remdesivir) administration with anti-inflammatory therapy reduces the TMPRSS2 blood level in moderate COVID-19, IL-6 in severe COVID-19 course, and fibrinogen A- and D-dimers in both groups. The proposed treatment does not significantly affect the concentration of endothelin-1, but a decrease in procalcitonin associated with additional antibacterial use was observed, especially in severe COVID-19.

COVID-19 remains a global health challenge, with severe cases often leading to complications and fatalities. The objective of this study was to assess supervised machine learning algorithms for predicting severe COVID-19 based on demographic, clinical, biochemical, and genetic variables, with the aim of identifying the most informative prognostic markers. For Machine Learning (ML) analysis, we utilized a dataset comprising 226 observations with 68 clinical, biochemical, and genetic features collected from 226 patients with confirmed COVID-19 (54—moderate, 142—severe and 30 with mild disease). The target variable was disease severity (mild, moderate, severe). The feature set included demographic variables (age, sex), genetic markers (single-nucleotide polymorphisms (SNPs) in FGB (rs1800790), NOS3 (rs2070744), and TMPRSS2 (rs12329760)), biochemical indicators (IL-6, endothelin-1, D-dimer, fibrinogen, among others), and clinical parameters (blood pressure, body mass index, comorbidities). The target variable was disease severity. To identify the most effective predictive models for COVID-19 severity, we systematically evaluated multiple supervised learning algorithms, including logistic regression, k-nearest neighbors, decision trees, random forest, gradient boosting, bagging, naïve Bayes, and support vector machines. Model performance was assessed using accuracy and the area under the receiver operating characteristic curve (AUC-ROC). Among the predictors, IL-6, presence of depression/pneumonia, LDL cholesterol, AST, platelet count, lymphocyte count, and ALT showed the strongest correlations with severity. The highest predictive accuracy, with negligible error rates, was achieved by ensemble-based models such as ExtraTreesClassifier, HistGradientBoostingClassifier, BaggingClassifier, and GradientBoostingClassifier. Notably, decision tree models demonstrated high classification precision at terminal nodes, many of which yielded a 100% probability for a specific severity class.

Background. The level of antiinfective protection is important in the comprehensive assessment of the immune status of patients, the study of which will provide an opportunity to develop a high-quality set of therapeutic and preventive measures to improve the effectiveness of medical care for patients with COVID-19. Aim: to conduct a comprehensive analysis of the level of nonspecific antiinfective protection in patients with COVID-19 depending on the polymorphism of the genes TMPRSS2 (C-allele; rs12329760), FGB (G-allele; rs1800790) and eNOS (T-allele; rs2070744), the severity of the disease and the combination with comorbidities. Materials and methods. We examined 204 patients with coronavirus infection who were hospitalized in the Infectious Diseases Department of the Uman Central City Hospital during 2021-2023, among the patients there were 51.97% (106) women, 48.03% (98) men, the average age of patients was 55.93±8.75 years. Comorbidity was retrospectively established in patients participating in the cohort study: 82 patients had concomitant cardiovascular disease; 46 patients were diagnosed with endocrine pathology; 76 patients had other comorbidities, which were grouped into one group “Other comorbidities”. The polymorphism of the TMPRSS2 (rs12329760), FGB (rs1800790) and NOS3 (rs2070744) genes was investigated by real-time polymerase chain reaction (Real Time PCR) in 96 patients. The level of nonspecific antiinfective protection of patients was determined by the following indicators: neutrophil granulocyte response, neutrophil-lymphocyte ratio, neutrophil shift index, neutrophil-monocyte ratio, etc. Results. It has been established that the reactive response of neutrophil granulocytes (NG) is higher in patients with COVID-19 who carry the wild G-allele (especially the GG genotype) of the FGB gene (rs1800790) - by 60, 0% (p=0.007), TT-genotype of the TMPRSS2 gene (rs12329760) - by 41.38% (p=0.012) and wild T-allele of the NOS3 gene (rs2070744) - by 29.87% (p=0.046). Severe and, to a lesser extent, moderate COVID-19 is accompanied by a lower level of cellular nonspecific resistance - by 34.33% (p<0.001), nonspecific reactivity and reactive response - by 45, 34% (p=0.002) and 15.02%, with a worse response to endo- and exo-intoxication in coronavirus infection with lower leukocyte intoxication indices (LII) by 29.56-41.50% (p≤0.049-0.003). Comorbidities significantly worsen the clinical and laboratory course of COVID-19: the lowest cellular reactivity with the highest reactive response of NG was found in comorbidity with cardiovascular disease against the background of more severe endogenous intoxication - by 38.60% (p<0.001) and 30.21-40.0% (p≤0.032-0.017), respectively. Conclusion. Polymorphism of FGB (rs1800790), TMPRSS2 (rs12329760), NOS3 (rs2070744) genes, disease severity and comorbidities have different effects on nonspecific antiinfective protection in patients with COVID-19.

Objective — to establish and evaluate the impact of comorbid pathology and the severity of the clinical course on the activity of anti-infective protection in patients with coronavirus disease 2019 (COVID-19), based on the analysis of the absolute and relative counts of major immune cell populations in peripheral blood. Materials and methods. A cross-sectional prospective study was conducted involving 204 patients with COVID-19-associated pneumonia of mild, moderate and severe stages. The cohort included 106 (51.97 %) women and 98 (48.03 %) men, with an average age of (55.93 ± 8.75) years. Anti-infective ­protection was studied using comprehensive clinical blood analysis, including the count of major immune-competent cells. Patients were categorised into groups based on comorbi­dity, taking into account the predominant concurrent pathology at the time of examination (endocrine, cardiovascular or other). Results and discussion. More severe COVID-19 cases were characterised by leukopenia, relative and absolute granulocytopenia, neutropenia, a slight hyporegenerative nuclear shift to the right and a reduction in the number of segmented neutrophils by 24.63—34.72 % (p ≤ 0.047—0.009) and eosinophilic granulocytes by 52.94—70.59 % (p ≤ 0.004—0.001). This was accompanied by relative and absolute agranulocytosis due to lymphocytosis (by 20.10—63.33 %; p ≤ 0.05—0.003) and monocytosis (by 40.0—74.12 %; p ≤ 0.046—0.049), indicating an active inflammatory infectious process of viral etiology against a background of decreased resistance and increased activity of the lymphocyte-macrophage link with the beginning of the formation of specific immune protection (cellular and humoral response to coronavirus intervention). Mild cases of COVID-19 showed a higher absolute count of peripheral blood granulocytes (by 48.25 %; p = 0.018), neutrophils, particularly segmented neutrophils and eosinophilic granulocytes, compared to moderate and severe cases (by 32.36—53.18 % (p ≤ 0.049—0.01) and 3.4 times (p ≤ 0.005—0.002)) and the lowest content of monocytes (by 35.41—42.57 %; p ≤ 0.049—0.046). In cases with concurrent endocrine and cardiological pathologies against a background of a more severe clinical course of COVID-19, immunoinflammatory changes intensified due to absolute and relative leukopenia, neutrophilic granulocytopenia, neutropenia, with the presence of relative lymphocytosis and monocytosis, and normal ESR indicators, confirming the inflammatory process of viral etiology, which, in the absence of treatment, may tend to form post-COVID and/or long-term effects of COVID-19 with multisystem involvement. Conclusions. The study found an enhancement of the immunoinflammatory response and an increase in the depletion of cellular factors of non-specific anti-infective protection with the progression of the clinical manifestations of COVID-19, particularly against the backdrop of comorbid endocrine and/or cardiological pathology.

Background. In the pathogenesis of COVID-19 development, cellular and general reactivity of the patient's body in response to exo- and endo-intoxication are important indicators, they are diagnostic markers of the severity of the disease. Aim: to find out and analyze the effect of gene polymorphism, severity of the clinical course of the disease and combination with comorbidities on the cellular and general body reactivity of patients with COVID-19. Materials and methods. The study included 204 patients with mild, moderate, and severe COVID-19-associated pneumonia who had comorbidities: cardiovascular disease (82 patients), endocrinopathy (46 patients), and comorbidities of the ENT organs, connective tissue, gastrointestinal tract, chronic kidney disease (CKD), who were grouped into the group "other comorbidities (76 patients). Among the patients were 51.97% (106) women and 48.03% (98) men. The average age of patients was 55.93±8.75 years. The polymorphism of the TMPRSS2 (rs12329760), FGB (rs1800790) and NOS3 (rs2070744) genes was investigated by real-time polymerase chain reaction (Real Time PCR). The level of cellular and general reactivity of the body of patients with coronavirus infection was determined by the cellular resistance index and leukocyte indices of intoxication (LII) according to J.Y. Kalf-Kalf, Reis, Himich, modified leukocyte index, intoxication index, hematological index of intoxication according to V.S. Vasiliev and nuclear index of endotoxemia. Results. It was found that patients with coronavirus infection carry mutational T-alleles of the gene (especially TT genotype) of the TMPRSS2 gene (rs12329760), A-allele of the FGB gene (rs1800790) and T-allele of the NOS3 gene (rs2070744) have the highest level of cellular resistance and cellular reactivity in response to endo- and exo-intoxication, which leads to a probable decrease in intoxication and is an adaptive defense response of the body. It was found that in the mild clinical course of coronavirus infection, the highest level of cellular reactivity and cellular resistance is observed, in the moderate course, the cellular reactivity of the body decreases by 81.34%, and in the severe course - by 45.35%, while high to moderate endo- and exo-intoxication, respectively, persists. In comorbidity with endocrinopathies or cardiovascular diseases (CVD), lower cellular resistance (especially in CVD) was found than in the combination of COVID-19 with other comorbidities in the remission/compensation phase - by 32, 64% (p<0.001) and 38.60% (p<0.001) against the background of higher endogenous intoxication according to the modified intoxication index and Reiss LI - by 30.21-40.0% (p≤0.032-0.017), respectively. Conclusion. The severity of the clinical course, the presence of comorbidities, polymorphism of the genes TMPRSS2 (rs12329760), FGB (rs1800790), NOS3 (rs2070744) have a multidirectional effect on cellular and general reactivity in patients with COVID-19.