No abstract

Aim. To study the epidemiological and clinical features of COVID-19 among patients with tuberculosis.Materials and Methods. We studied the incidence of COVID-19 in various population groups in Kemerovo Region in 2020 (from March, 13 to December, 31). The study cohort consisted of 3929 tuberculosis patients, including 113 with a verified COVID-19 diagnosis. The control cohort included tuberculosis-free subjects with COVID-19 (25,774 individuals). Out of these subjects, we enrolled 71 patients with tuberculosis and 71 age- and gender-matched controls. All patients underwent complete blood count, urinalysis, biochemical analysis, and coagulation testing.Results. The incidence of COVID-19 in patients with tuberculosis was 2.96-fold higher than in the tuberculosis-free population (2876.05 and 971.17 per 100,000 population, respectively). In patients with tuberculosis, the highest incidence of COVID-19 was recorded in two age categories: from 18 to 29 years and ≥ 65 years of age. In tuberculosis patients, COVID-19 was mostly mild, was characterised by a 9.2-fold lower frequency of pneumonia, 11.8-fold less use of antibiotics, and oxygen therapy was required only in 1.41% of cases in comparison with 16.9% in the tuberculosis-free subjects. In addition, patients with tuberculosis less often suffered from hyperthermia, cough and weakness. Regarding the comorbid conditions, patients with tuberculosis showed lower prevalence of arterial hypertension, chronic heart failure, peripheral artery disease, and obesity. Further, patients with tuberculosis generally had higher glomerular filtration rate and rarely had neutrophilia or lymphopenia when compared with the control individuals with COVID-19, although having higher fibrinogen and aspartate aminotransferase serum levels.Conclusion. Tuberculosis is a risk factor of COVID-19 but not a predictor of morbidity and mortality from this disease.

Mycobacterium tuberculosis is the causative agent of human tuberculosis; enabling multilayered mechanisms to evade from immune response along with reactivation of the process with subsequent pathogen dissemination. Modification of immune responses through imbalanced intracellular signaling pathways and reprogramming of differential gene expression is one of such mechanisms. Modification targets for M. tuberculosis are the genes which products are involved in lipid metabolism and apoptosis, a key to eliminate intracellular pathogens. here, we review the current scientific data related to this problem: the results of studies published in domestic and foreign literature from the years 2003 to 2022 were systematized and summarized; data on the role of a number of molecular mechanisms regulating lipid metabolism and apoptosis in human TB-infection; discuss contemporary ideas about the importance of the VDR signaling cascade controlled by the vitamin D-axis counteracting M. tuberculosis infection, its course and outcome. In addition, there are provided the data on the main M. tuberculosis genetic lines common in Siberia and the elements of the pathogen-related genetic structure that are important in the context of the topic. The effects of interplay and interactions of intracellular molecular cascades (VDR, NFKB, MAPK, NFAT5, AMPK, GR) are considered and analyzed, as well as their role in the differential expression of genes that ensure M. tuberculosis inactivation and elimination. Presenting the data confirming that one of the main strategies of mycobacterium immune evasion counteraction to apoptosis is implemented through altered VDR signaling pathway, including the epigenetic mechanisms occurring in the pathogen. Based on results of the analysis and summarized literature data (60 articles retrieved from eLIBRARY, PubMed), it is demonstrated that during the thousand-year history of co-evolution with human, M. tuberculosis acquired unique features of genetic organization and mastered the pathways of immune evasion using non-genomic and genomic mechanisms. Available publications confirm that one of the main strategies for M. tuberculosis survival in macrophages is to modify a balance between intracellular signaling cascades controlling the differential expression of genes that provide a proper immune response to infection, followed by pathogen elimination.

Fungi are opportunistic microorganisms that colonize all biotopes of the human body, including intestinal. In case of emerging adverse environmental factors (HIV infection, other immunodeficiencies, antibiotic therapy), these microbial representatives begin active reproduction, which might require prescribing antimycotics. Frequent use of the latter in clinical practice induces the development of drug resistance to antifungal drugs, which may impact on effectiveness of both the treatment of fungal infections and other diseases. The purpose of the study was to assess the pattern and spectrum of drug resistance of Candida genus in the intestinal biotope of patients with respiratory tuberculosis and identify risk factors for developing total fungal drug resistance to antimycotic drugs. Material and methods. There were enrolled 21 patients with respiratory tuberculosis. Pattern of the fungal species diversity for the Candida genus isolated from faeces was evaluated, and the spectrum of relevant drug resistance to antimycotic drugs was determined. Patients (n=21) were divided into 2 groups: with (n=10) and without (n=11) total resistance to antimycotics, after which the main risk factors for its development were identified. Results. Members of the Candida genus were isolated from all patients examined, wherein pure cell cultures were characterized by high level of antimycotics resistance. Resistance to three drugs was noted in 1 culture (4.8%), to four in 10 cultures (47.6%), also found in 10 cultures to the entire drug panel (47.6%). During statistical processing, the data were obtained on affecting formation of total resistance to antimycotics of concomitant pathology of the gastrointestinal tract, the presence of a clinically significant dyspeptic syndrome, a history of antimycotic therapy, HIV infection with severe immunodeficiency, and some decrease in the peripheral blood CD4+ lymphocyte count. Conclusions. Fungi of the Candida genus isolated from tuberculosis patients were characterized by high level of resistance to antimycotics. Total resistance was observed in 47.6% of patients. In addition, the major fungi colonizing the intestines of tuberculosis patients were found to be Candida albicans species. The risk factors for the development of total antifungal resistance included: chronic enterocolitis, dyspeptic syndrome, peripheral blood CD4+ lymphocyte count lower than 350 cells/l, and history of antimycotic therapy.