Aim Despite the regular heart damage in patients with coronavirus pneumonia caused by SARS-Cov-2, a possibility of developing lymphocytic myocarditis as a part of COVID-19 remains unsubstantiated. The aim of this study was to demonstrate a possibility of lymphocytic myocarditis and to study its morphological features in patients with the novel coronavirus infection (COVID-19) with a severe course. Material and methods  Postmortem data were studied for 5 elderly patients (74.8±4.4 years; 3 men and 2 women) with the novel coronavirus infection and bilateral, severe polysegmental pneumonia (stage 3–4 by computed tomography). COVID-19 was diagnosed based on the typical clinical presentation and positive polymerase chain reaction test in nasopharyngeal swabs. All patients were treated in different hospitals repurposed for the treatment of patients with COVID-19. A standard histological study was performed with hematoxylin and eosin, toluidine blue, and van Gieson staining. Serial paraffin slices were studied immunohistochemically with antibodies to CD3, СD68, CD20, perforin, and toll-like receptors (TLR) 4 and 9. Results In none of the cases, myocarditis was suspected clinically, added to the diagnosis or indicated as a possible cause of death. IHD and acute myocardial infarction were mentioned as error diagnoses not confirmed by the postmortem examination. The morphological examination of the heart identified signs of lymphocytic myocarditis consistent with Dallas criteria for this diagnosis. Myocardial infiltrate was characterized in detail, and a combined inflammatory damage of endocardium and pericardium was described. The immunohistochemical study with cell infiltrate typing confirmed the presence of CD3-positive Т lymphocytes and the increased expression of TLR-4. A picture of coronaritis, including that with microvascular thrombosis, was found in all cases. Conclusion A possibility for development of lymphocytic viral myocarditis in COVID-19 was confirmed morphologically and immunohistochemically. Specific features of myocarditis in COVID-19 include the presence of coronaritis and a possible combination of myocarditis with lymphocytic endo- and pericarditis.

Tuberculosis (TB) is a significant problem of public health both in Russia and abroad. About one third of the world’s population is infected with Mycobacterium tuberculosis. Every year more than 10 million new TB cases are registered in the world, and about 1.7 million people die from TB. In the Russian Federation, due to the measures taken by the Government and health authorities the epidemic TB situation has been noticeably improved since the sharp deterioration in the 90s of the last century. At the same time, the spread of drug-resistant TB and its low treatment effectiveness, the spread of combined HIV and TB infection reduces the effectiveness of anti-tuberculosis interventions. The research conducted by CTRI, the WHO Collaborating Center for TB in the Russian Federation, is aimed at solving such urgent problems as studying latent infection mechanisms, developing new test systems for accelerated diagnostics of drug resistance, clinical approbation and introduction of short effective regimens of chemotherapy, developing new antituberculosis agents. The achieved successes in the study of tuberculosis in the 21st century creates preconditions for eliminating its epidemic both in Russia and the world, though suggesting imminent breakthrough for tuberculosis is a hasty conclusion.

Widespread drug-resistant tuberculosis is a global challenge that has a potential to have a negative impact on the global TB situation. Rapid TB diagnosis and early initiation of effective treatment based on the individualized chemotherapy regimens underpin efforts in prevention of further spread of tuberculosis. Microbiological methods of TB diagnosis that provide evidence of the TB process etiology and identify drug susceptibility of the pathogen play a very important role. The review covers the current and emerging methods of the microbiological TB diagnosis including conventional microbiological (microscopy of diagnostic material, cultural studies on solid media and culture fluids) and modern molecular genetic tests (DNA strips, biological microchips, multiplex PCR, GeneXpert and diagnostic systems of the new generation and point-of-care tests) and demonstrates the role of the described methods in the diagnostic TB laboratory algorithm. The example of the Microbiology Department of the Central TB Research Institute illustrates the effectiveness of modern developments in the diagnosis of drug-resistant tuberculosis and their impact on improving treatment success in the clinical departments of the CTRI. The review presents further prospects of drug-resistant TB diagnosis in relation to the new technologies such as Next Generation Sequencing. The conclusion summarizes information on the current state of microbiological diagnosis of drug-resistant tuberculosis and emphasizes the importance of developing and introducing new technologies into the diagnostic process.

Background. The effect on the activity of the multidrug resistance protein P-glycoprotein (P-gp, MDR1 gene) in pro-inflammatory (M1) human macrophages is considered one of the promising strategies for increasing the effectiveness of the treatment in patients with pulmonary tuberculosis: P-gp activity is considered a factor that reduces intracellular accumulation of rifampicin (RIF), a substrate for P-gp. The aim of this work was to reveal the effect of the therapeutic concentration of RIF on the activity of P-gp in M1 human macrophages. The objectives were as follows: to determine the expression levels of the MDR1 gene, P-gp protein, as well as its functional activity at different periods of cell differentiation and under the influence of RIF.Material and methods. The following cell lines were used in the work: suspension cells of promonocytic leukemia THP-1 and THP-1 macrophages induced by phorbol ether according to the pro-inflammatory phenotype. Suspension cells of myeloid leukemia K562/IS-9 transfected with the MDR1 gene were used as a comparison group. An important factor is the choice of the experimental concentration of RIF: the average concentration of the drug in patients with pulmonary tuberculosis was 10 µg/ml. The methods of RT-PCR, immunocytochemistry, and flow cytometry were used in the work.Results and discussion. The induction of MDR1 gene expression in M1 macrophages under short-term exposure to a therapeutic concentration of RIF was revealed. This effect is typical only for THP-1 macrophages, in which a significant functional activity of P-gp is registered. This induction does not occur in the cells with no detectable P-gp activity (THP-1 suspension cells). This indicates the presence of different mechanisms of RIF influence on MDR1, which can be used to develop a strategy for P-gp inhibition in inflammatory macrophages.Conclusion. Given the key role of macrophages in tuberculosis, further evaluation of MDR1/P-gp in the surgical material of patients with pulmonary tuberculosis is necessary, which makes it possible to draw a conclusion that it is necessary to develop and apply drug strategies aimed at blocking the functional activity of P-gp and choosing more effective anti-tuberculosis therapy regimens.

Во всем мире табакокурение и заболевания туберкулезом легких представляют собой проблему здравоохранения на протяжении длительного времени. За последние годы наблюдался значительный рост лекарственной устойчивости микобактерии туберкулеза, что приводит к снижению эффективности проводимой терапии. Также неуклонно растет и распространенность курения среди пациентов с туберкулезом легких. В связи с этим является актуальным проанализировать связь табакокурения и клинического течения туберкулезной инфекции. ЦЕЛЬ ИССЛЕДОВАНИЯ Провести количественную оценку ассоциации табакокурения с основными клиническими формами и тяжестью течения туберкулеза легких. МАТЕРИАЛ И МЕТОДЫ Проведен анализ медицинской документации пациентов в отделе фтизиатрии ФГБНУ ЦНИИТ за период с 2018 по 2020 г. В группу исследования были включены 60 пациентов в возрасте 18 лет и старше с подтвержденным туберкулезом легких, из которых 31 являлся курильщиком и 29 никогда не курили. РЕЗУЛЬТАТЫ Табакокурение ассоциировано с более тяжелым течением туберкулеза легких, требующим длительной интенсивной терапии. Статистически значимо табакокурение связано с фиброзно-кавернозной и другими распространенными формами туберкулеза легких, наличием бактериовыделения, которые встречаются у курящих больных соответственно в 5, 6,5 и 3,5 раза чаще, по сравнению с некурящими. Доказано, что у курящих пациентов статистически значимо в 3 раза чаще присутствуют сопутствующие заболевания, что может являться причиной более тяжелого течения туберкулеза легких и затрудняет лечение. Табакокурение у пациентов с туберкулезом легких сопровождается бронхообструктивными нарушениями легких. ЗАКЛЮЧЕНИЕ Таким образом, табакокурение является значимым фактором, ассоциированным с распространенными клиническими формами туберкулеза легких и тяжелым течением заболевания.

The lack of simple, rapid diagnostic tests for isoniazid-resistant rifampicin-susceptible tuberculosis infection (Hr-TB) can result in low treatment efficacy and further amplification of drug resistance. Based on the clinical data, this study sought to estimate the prevalence of Hr-TB in the general population and characterize the phenotypic susceptibility and genetic determinants of isoniazid resistance in M. tuberculosis strains. Molecular-genetic and culture-based drug susceptibility tests were performed on M. tuberculosis isolates and M. tuberculosis DNA obtained from the patients with pulmonary TB undergoing treatment at the Central Tuberculosis Research Institute between 2011 and 2018. The tests revealed that Hr-TB accounted for 12% of all TB cases in the studied sample. Hr-TB strains were either resistant to isoniazid only (45%) or had multiple resistance to 2–6 anti-TB agents. Resistance to isoniazid was caused by mutations in the katG gene. Based on the literature analysis and our own observations, we emphasize the importance of developing simple molecular drug susceptibility tests capable of detecting simultaneous resistance to rifampicin and isoniazid and the necessity of their translation into clinical practice.