Efficacy of AI-Guided (GenAISTM) Dietary Supplement Prescriptions versus Traditional Methods for Lowering LDL Cholesterol: A Randomized Parallel-Group Pilot Study.

Emerging evidence suggests that personalized dietary supplement regimens can significantly influence lipid metabolism and cardiovascular risk. The efficacy of AI-guided dietary supplement prescriptions, compared with standard physician-guided prescriptions, remains underexplored. In a randomized, parallel-group pilot study, 70 patients aged 40-75 years with LDL-C levels between 70 and 190 mg/dL were enrolled. Participants were randomized to receive either AI-guided dietary supplement prescriptions or standard physician-guided prescriptions for 90 days. The primary endpoint was the percent change in LDL-C levels. Secondary endpoints included changes in total cholesterol, HDL-C, triglycerides, and hsCRP. Supplement adherence and side effects were monitored. Sixty-seven participants completed the study. The AI-guided group experienced a 25.3% reduction in LDL-C levels (95% CI: -28.7% to -21.9%), significantly greater than the 15.2% reduction in the physician-guided group (95% CI: -18.5% to -11.9%; p < 0.01). Total cholesterol decreased by 15.4% (95% CI: -19.1% to -11.7%) in the AI-guided group compared with 8.1% (95% CI: -11.5% to -4.7%) in the physician-guided group (p < 0.05). Triglycerides were reduced by 22.1% (95% CI: -27.2% to -17.0%) in the AI-guided group versus 12.3% (95% CI: -16.7% to -7.9%) in the physician-guided group (p < 0.01). HDL-C and hsCRP changes were not significantly different between groups. The AI-guided group received a broader variety of supplements, including plant sterols, omega-3 fatty acids, red yeast rice, coenzyme Q10, niacin, and fiber supplements. Side effects were minimal and comparable between groups. AI-guided dietary supplement prescriptions significantly reduce LDL-C and triglycerides more effectively than standard physician-guided prescriptions, highlighting the potential for AI-driven personalization in managing hypercholesterolemia.

A Novel Multiplex LAMP Assay for the Detection of Respiratory Human Adenoviruses.

Human adenoviruses (HAdVs) are common pathogens that are associated with a variety of diseases, including respiratory tract infections (RTIs). Without reliable, fast, and cost-effective detection methods for HAdVs, patients may be misdiagnosed and inappropriately treated. To address this problem, we have developed a multiplex loop-mediated isothermal amplification (LAMP) assay for the detection of the species Human adenovirus B (HAdV-B), Human adenovirus C (HAdV-C) and Human adenovirus E (HAdV-E) that cause RTIs. This multiplexing approach is based on the melting curve analysis of the amplicons with a specific melting temperature for each HAdV species. Without the need for typing of HAdVs, the LAMP results can be visually detected using colorimetric analysis. The assay reliably detects at least 375 copies of HAdV-B and -C and 750 copies of HAdV-E DNA per reaction in less than 35 min at 60 °C. The designed primers have no in silico cross-reactivity with other human respiratory pathogens. Validation on 331 nasal swab samples taken from patients with RTIs showed a 90-94% agreement rate with our in-house multiplex quantitative polymerase chain reaction (qPCR) method. Concordance between the quantitative and visual LAMP was 99%. The novel multiplexed LAMP could be an alternative to PCR for diagnostic purposes, saving personnel and equipment time, or could be used for point-of-care testing.

Vitamin D Metabolism Parameters and Cytokine Profile in COVID-19 Patients with Bolus Cholecalciferol Supplementation.

Recent studies have demonstrated the relationship between vitamin D deficiency, infection severity and mortality from COVID-19. This study aimed to analyze the vitamin D metabolites and cytokine expression levels of COVID-19 patients who were hospitalized with bolus cholecalciferol supplementation. MATERIALS AND METHODS: This study represents the next stage of the open-label randomized pilot conducted by the Almazov National Medical Research Centre. A total of 44 hospitalized patients, comparable in demographic, clinical, laboratory and instrumental baseline characteristics, with moderate/severe COVID-19 were included. All patients had similar doses of concomitant corticosteroid therapy. Twenty-two patients received 50,000 IU cholecalciferol on the first and eighth days of hospitalization. The serum 25(OH)D, 1,25(OH)2D and 28 plasma cytokines were estimated for each group initially and on the ninth day of hospitalization. RESULTS: Initially, there were no differences in the 1,25(OH)2D and cytokine levels in patients with vitamin D deficiency and normal 25(OH)D. Bolus cholecalciferol therapy at a total dose of 100,000 IU led to an increase in 25(OH)D levels in hospitalized patients with COVID-19, while the levels of the active metabolite (1,25(OH)2D) did not show significant differences between the groups or in its increased level over time, regardless of cholecalciferol supplementation. Furthermore, cholecalciferol supplementation at a total dose of 100,000 IU did not affect the majority of the cytokines estimated on the ninth day of hospitalization, except for the pro-inflammatory marker IL-1b, the concentration of which was lower in the group of patients without vitamin D supplementation. CONCLUSIONS: The 25(OH)D level was positively associated with an anti-inflammatory immune response, but cholecalciferol supplementation at a total dose of 100,000 IU did not affect the active-form vitamin D or cytokine expression levels. This fact may be explained by the impact of corticosteroid therapy, and it requires further investigation in a post-COVID-19 context.

Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (SolowaysTM) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized Controlled Trial.

Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5'-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40-75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo (p < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, p < 0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, p < 0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, p < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, p < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, p < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, p < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.

Are Endomyocardial Ventricular Biopsies Useful for Assessing Myocardial Fibrosis?

Myocardial fibrosis is an important factor in the progression of cardiovascular diseases. However, there is still no universal lifetime method of myocardial fibrosis assessment that has a high prognostic significance. The aim of the study was to determine the significance of ventricular endomyocardial biopsies for the assessment of myocardial fibrosis and to identify the severity of myocardial fibrosis in different cardiovascular diseases. Material and Methods: Endomyocardial biopsies (EMBs) of 20 patients with chronic lymphocytic myocarditis (CM), endomyocardial fragments obtained during septal reduction of 21 patients with hypertrophic cardiomyopathy (HCM), and 36 patients with a long history of hypertensive and ischemic heart disease (HHD + IHD) were included in the study. The control group was formed from EMBs taken on 12-14 days after heart transplantation (n = 28). Also, for one patient without clinical and morphological data for cardiovascular pathology, postmortem myocardial fragments were taken from typical EMB and septal reduction sites. The relative area of fibrosis was calculated as the ratio of the total area of collagen fibers to the area of the whole biopsy. Endocardium and subendocardial fibrosis were not included in the total biopsy area. Results: The relative fibrosis area in the EMBs in the CM patient group was 5.6 [3.3; 12.6]%, 11.1 [6.6; 15.9]% in the HHD + IHD patient group, 13.4 [8.8; 16.7]% in the HCM patient group, and 2.7 [1.5; 4.6]% in the control group. When comparing the fibrosis area of the CM patients in repeat EMBs, it was found that the fibrosis area in the first EMBs was 7.6 [4.8; 12.0]%, and in repeat EMBs, it was 5.3 [3.2; 7.6]%. No statistically significant differences were found between the primary and repeat EMBs (p = 0.15). In ROC analysis, the area of fibrosis in the myocardium of 1.1% (or lower than one) was found to be highly specific for the control group of patients compared to the study patients. Conclusions: EMB in the assessment of myocardial fibrosis has a questionable role because of the heterogeneity of fibrotic changes in the myocardium.

Bronchial Asthma and COVID-19: Etiology, Pathological Triggers, and Therapeutic Considerations.

Bronchial asthma (BA) continues to be a difficult disease to diagnose. Various factors have been described in the development of BA, but to date, there is no clear evidence for the etiology of this chronic disease. The emergence of COVID-19 has contributed to the pandemic course of asthma and immunologic features. However, there are no unambiguous data on asthma on the background and after COVID-19. There is correlation between various trigger factors that provoke the development of bronchial asthma. It is now obvious that the SARS-CoV-2 virus is one of the provoking factors. COVID-19 has affected the course of asthma. Currently, there is no clear understanding of whether asthma progresses during or after COVID-19 infection. According to the results of some studies, a significant difference was identified between the development of asthma in people after COVID-19. Mild asthma and moderate asthma do not increase the severity of COVID-19 infection. Nevertheless, oral steroid treatment and hospitalization for severe BA were associated with higher COVID-19 severity. The influence of SARS-CoV-2 infection is one of the protective factors. It causes the development of severe bronchial asthma. The accumulated experience with omalizumab in patients with severe asthma during COVID-19, who received omalizumab during the pandemic, has strongly suggested that continued treatment with omalizumab is safe and may help prevent the severe course of COVID-19. Targeted therapy for asthma with the use of omalizumab may also help to reduce severe asthma associated with COVID-19. However, further studies are needed to prove the effect of omalizumab. Data analysis should persist, based on the results of the course of asthma after COVID-19 with varying degrees of severity.

COVID-19 and Tuberculosis: Mathematical Modeling of Infection Spread Taking into Account Reduced Screening.

The COVID-19 pandemic resulted in the cessation of many tuberculosis (TB) support programs and reduced screening coverage for TB worldwide. We propose a model that demonstrates, among other things, how undetected cases of TB affect the number of future M. tuberculosis (M. tb) infections. The analysis of official statistics on the incidence of TB, preventive examination coverage of the population, and the number of patients with bacterial excretion of M. tb in the Russian Federation from 2008 to 2021 is carried out. The desired model can be obtained due to the fluctuation of these indicators in 2020, when the COVID-19 pandemic caused a dramatic reduction in TB interventions. Statistical analysis is carried out using R v.4.2.1. The resulting model describes the dependence of the detected incidence and prevalence of TB with bacterial excretion in the current year on the prevalence of TB with bacterial excretion in the previous year and on the coverage of preventive examinations in the current and previous years. The adjusted coefficient of model determination (adjusted R-squared) is 0.9969, indicating that the model contains almost no random component. It clearly shows that TB cases missed due to low screening coverage and left uncontrolled will lead to a significant increase in the number of new infections in the future. We may conclude that the obtained results clearly demonstrate the need for mass screening of the population in the context of the spread of TB infection, which makes it possible to timely identify patients with TB with bacterial excretion.

Imbalance between Actin Isoforms Contributes to Tumour Progression in Taxol-Resistant Triple-Negative Breast Cancer Cells.

The widespread occurrence of breast cancer and its propensity to develop drug resistance highlight the need for a comprehensive understanding of the molecular mechanisms involved. This study investigates the intricate pathways associated with secondary resistance to taxol in triple-negative breast cancer (TNBC) cells, with a particular focus on the changes observed in the cytoplasmic actin isoforms. By studying a taxol-resistant TNBC cell line, we revealed a shift between actin isoforms towards γ-actin predominance, accompanied by increased motility and invasive properties. This was associated with altered tubulin isotype expression and reorganisation of the microtubule system. In addition, we have shown that taxol-resistant TNBC cells underwent epithelial-to-mesenchymal transition (EMT), as evidenced by Twist1-mediated downregulation of E-cadherin expression and increased nuclear translocation of ß-catenin. The RNA profiling analysis revealed that taxol-resistant cells exhibited significantly increased positive regulation of cell migration, hormone response, cell-substrate adhesion, and actin filament-based processes compared with naïve TNBC cells. Notably, taxol-resistant cells exhibited a reduced proliferation rate, which was associated with an increased invasiveness in vitro and in vivo, revealing a complex interplay between proliferative and metastatic potential. This study suggests that prolonged exposure to taxol and acquisition of taxol resistance may lead to pro-metastatic changes in the TNBC cell line.

Actin-Dependent Mechanism of Tumor Progression Induced by a Dysfunction of p53 Tumor Suppressor.

Cancer cell aggressiveness, marked by actin cytoskeleton reconfiguration critical for metastasis, may result from an imbalanced ratio favoring γ-actin. Dysfunctional p53 emerges as a key regulator of invasiveness and migration in various cancer cells, both in vitro and in vivo. P53 inactivation (via mutants R175H, R248W, R273H, or TP53 repression) significantly enhanced the migration, invasion, and proliferation of human lung adenocarcinoma A549 cells in vitro and in vivo, facilitating intrapulmonary xenograft metastasis in athymic mice. Conversely, wild-type TP53 (TP53 WT) overexpression in p53-deficient non-small- cell lung cancer (NSCLC) H1299 cells substantially reduced proliferation and migration in vitro, effectively curbing orthotopic tumorigenicity and impeding in vivo metastasis. These alterations in cell motility were closely associated with actin cytoskeleton restructuring, favoring γ-actin, and coincided with ERK1/2-mediated signaling activation, unveiling an innovative regulatory mechanism in malignancy progression. Cancer cell aggressiveness, driven by actin cytoskeleton reorganization and a shift towards γ-actin predominance, may be regulated by p53 dysfunction, thereby providing novel insight into tumor progression mechanisms.

The brain serotonin system in autism.

Autism spectrum disorders (ASDs) are among the most common neurodevelopmental diseases. These disorders are characterized by lack of social interaction, by repetitive behavior, and often anxiety and learning disabilities. The brain serotonin (5-HT) system is known to be crucially implicated in a wide range of physiological functions and in the control of different kinds of normal and pathological behavior. A growing number of studies indicate the involvement of the brain 5-HT system in the mechanisms underlying both ASD development and ASD-related behavioral disorders. There are some review papers describing the role of separate key players of the 5-HT system in an ASD and/or autistic-like behavior. In this review, we summarize existing data on the participation of all members of the brain 5-HT system, namely, 5-HT transporter, tryptophan hydroxylase 2, MAOA, and 5-HT receptors, in autism in human and various animal models. Additionally, we describe the most recent studies involving modern techniques for in vivo regulation of gene expression that are aimed at identifying exact roles of 5-HT receptors, MAOA, and 5-HT transporter in the mechanisms underlying autistic-like behavior. Altogether, results of multiple research articles show that the brain 5-HT system intimately partakes in the control of some types of ASD-related behavior, and that specific changes in a function of a certain 5-HT receptor, transporter, and/or enzyme may normalize this aberrant behavior. These data give hope that some of clinically used 5-HT-related drugs have potential for ASD treatment.

Assessment of Comorbidity in Patients with Drug-Resistant Tuberculosis.

A wide range of comorbidities, especially in multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) patients, markedly complicates selecting effective treatment of tuberculosis (TB) and preventing the development of adverse events. At present, it is impossible to assess the severity of comorbid pathologies and develop indications for the administration of accompanying therapy in TB patients. The aim of this study was to identify the difference in the range of comorbidities between patients with MDR-TB and XDR-TB and assess the impact of comorbidities on TB treatment. Materials and Methods: A retrospective, prospective study was conducted where 307 patients with MDR-TB and XDR-TB pulmonary tuberculosis aged 18 to 75 years who received eTB treatment from 2016 to 2021 in St. Petersburg hospitals were analyzed. The analysis showed that the comorbidity level in MDR-TB and XDR-TB patients with TB treatment success and treatment failure was comparable with the use of the Charlson Comorbidity Index (CCI). The CCI demonstrated declining data in terms of TB treatment outcome period in both groups. A slight predominance of CCI score (3 to 4 points) in XDR-TB (22.7%) vs. MDR-TB (15.4%) patients was found. In the case of an TB treatment failure, the CCI level in MDR-TB vs. XDR-TB patients was characterized by a significantly higher rate of low magnitude (ranging from 1 to 2 points) in 21.1% vs. 4.5% (p < 0.05), which was higher in XDR-TB patients (ranging from 4 to 5 points, in 10.0% vs. 0, χ2 = 33.7 (p < 0.01)). Chronic viral hepatitis B and C infection, cardiovascular pathology, chronic obstructive pulmonary disease, and chronic alcoholism were found to be significant comorbidity factors that influenced the TB treatment success. Conclusions: It is evident that XDR-TB patients comprise a cohort with the most severe disease course due to comorbidities impacting TB treatment efficacy. The obtained data pointed to the need to determine comorbidity severity in patients with drug-resistant Mbt prior to administering TB treatment schemes.

Expression of Cytoskeletal Proteins (GFAP, Vimentin), Proapoptotic Protein (Caspase-3) and Protective Protein (S100) in the Epileptic Focus in Adults and Children with Drug-Resistant Temporal Lobe Epilepsy Associated with Focal Cortical Dysplasia.

The European Commission of the International League Against Epilepsy (ILAE) has identified glial mechanisms of seizures and epileptogenesis as top research priorities. The aim of our study was to conduct a comparative analysis of the expression levels of cytoskeletal proteins (glial fibrillar acidic protein (GFAP) and vimentin), protective protein S100, and proapoptotic caspase-3 protein in patients with drug-resistant epilepsy (DRE) associated with focal cortical dysplasia (FCD). We aimed to investigate how the expression levels of these proteins depend on age (both in children and adults), gender, and disease duration, using immunohistochemistry. Nonparametric statistical methods were employed for data analysis. In the epileptic focus area of the cortex and white matter in patients with FCD-associated temporal lobe DRE, a higher level of expression of these proteins was observed. Age and gender differences were found for vimentin and S100. In the early stages of disease development, there was a compensatory sequential increase in the expression of cytoskeletal and protective proteins. In patients with DRE, depending on the disease duration, patterns of development of neurodegeneration were noted, which is accompanied by apoptosis of gliocytes. These results provide insights into epilepsy mechanisms and may contribute to improving diagnostic and treatment approaches.

High Risk of Heart Tumors after COVID-19.

An emergence of evidence suggests that severe COVID-19 is associated with an increased risk of developing breast and gastrointestinal cancers. The aim of this research was to assess the risk of heart tumors development in patients who have had COVID-19. METHODS: A comparative analysis of 173 heart tumors was conducted between 2016 and 2023. Immunohistochemical examination with antibodies against spike SARS-CoV-2 was performed on 21 heart tumors: 10 myxomas operated before 2020 (the control group), four cardiac myxomas, one proliferating myxoma, three papillary fibroelastomas, two myxofibrosarcomas, one chondrosarcoma resected in 2022-2023. Immunohistochemical analysis with antibodies against CD34 and CD68 was also conducted on the same 11 Post-COVID period heart tumors. Immunofluorescent examination with a cocktail of antibodies against spike SARS-CoV-2/CD34 and spike SARS-CoV-2/CD68 was performed in 2 cases out of 11 (proliferating myxoma and classic myxoma). RESULTS: A 1.5-fold increase in the number of heart tumors by 2023 was observed, with a statistically significant increase in the number of myxomas. There was no correlation with vaccination, and no significant differences were found between patients from 2016-2019 and 2021-2023 in terms of gender, age, and cardiac rhythm dis-orders. Morphological examination revealed the expression of spike SARS-CoV-2 in tumor cells, endothelial cells, and macrophages in 10 out of 11 heart tumors. CONCLUSION: The detection of SARS-CoV-2 persistence in endothelium and macrophages as well as in tumor cells of benign and malignant cardiac neoplasms, the increase in the number of these tumors, especially cardiac myxomas, after the pandemic by 2023 may indicate a trend toward an increased risk of cardiac neoplasms in COVID-19 patients, which re-quires further research on this issue and a search for new evidence.

A Key Role of CD8+ T Cells in Controlling of Tuberculosis Infection.

The main role in the control of tuberculosis infection is played by macrophages and Th1 and CD8+ T cells. The study aimed to identify the most diagnostically significant CD8+ T cell subsets in tuberculosis patients. METHODS: Peripheral blood samples from patients with clinical, radiological, and bacteriologically confirmed pulmonary tuberculosis (TB, n = 32) and healthy subjects (HC, n = 31) were collected and analyzed using 10-color flow cytometry. RESULTS: The frequency of the EM4 CD3+CD8+ cells was reduced in the peripheral blood of patients with pulmonary tuberculosis, while the relative and absolute number of EM1 CD3+CD8+ cells increased compared to the control group. CD57 expression was reduced in patients with pulmonary tuberculosis on EM1, EM2, and pE1 CD3+CD8+ cells, whereas the EM3 cells had a high level of CD57 expression. The relative and absolute number of Tc2 (CCR6-CXCR3-) cells in peripheral blood in patients with pulmonary tuberculosis was increased, while the frequency of Tc1 (CCR6-CXCR3+) was decreased, compared to healthy donors. CONCLUSIONS: Patients with pulmonary tuberculosis have an abnormal CD3+CD8+ cell profile and demonstrate their impaired maturation and functional activity.

The Features of COVID-19's Course and the Efficacy of the Gam-COVID-Vac Vaccine in Patients with Paroxysmal Nocturnal Hemoglobinuria.

COVID-19 and other infectious diseases can exacerbate the course of paroxysmal nocturnal hemoglobinuria (PNH). The efficacy and safety of the Gam-COVID-Vac vaccine in patients with PNH has not been adequately studied. A retrospective, observational, cohort, non-comparative study was performed to assess the course of COVID-19 as well as the safety and efficacy of the Gam-COVID-Vac (Sputnik V) vaccine in patients with paroxysmal nocturnal hemoglobinuria (PNH). The study included data from 52 patients with PNH aged 18 to 75 years, 38 of whom received background therapy with eculizumab (Elizaria®) between March 2020 and January 2022. COVID-19 was diagnosed according to the results of PCR testing. The patients were divided into two groups for comparison of the incidence of COVID-19. Group 1 included non-vaccinated patients with PNH, and Group 2 included patients vaccinated prior to the onset of COVID-19. According to vaccination, patients were subdivided into non-vaccinated and vaccinated groups without signs of previous COVID-19 at the beginning of the analyzed period, and patients vaccinated half a year or more after recovery from COVID-19. Testing for anti-SARS-CoV-2 IgG levels was carried out in patients with PNH in the year after their COVID-19. Tests for anti-SARS-CoV-2 RBD IgG levels were performed on vaccinated patients. In total, 28 (53.8%) of the enrolled patients had COVID-19, including asymptomatic forms in 7 (25%) and mild forms in 16 (57%) patients. A total of 22 (42.3%) patients were fully vaccinated with Gam-COVID-Vac, of which 13 (25%) patients were vaccinated without the signs of previous SARS-CoV-2infection, and 9 (17.3%) patients were vaccinated after COVID-19. The number of patients who had COVID-19 was about two times higher in Group 1 (non-vaccinated; 24) (61.5%), whereas in Group 2 (vaccinated), the number of patients with COVID-19 was only 4 (30.8%). The proportion and number of patients who did not have COVID-19 was higher in the group of vaccinated patients (9; 69.2%) than in the group of non-vaccinated patients (15; 38.5%) (p = 0.054). In patients who had been infected with COVID-19, maximum concentrations of anti-SARS-CoV-2 IgG were observed 2-3 months after the acute infection phase, followed by a gradual decline by month 9-10. The mean RBD IgG concentration was higher in the group of patients who had been infected by COVID-19 than in the group of patients without COVID-19 (p = 0.047). Therapy type, including eculizumab, did not have a significant impact on RBD IgG titers (p > 0.05). Hospitalization was required in five (18%) patients, all of whom had breakthrough hemolysis and severe lung damage on CT scans. After the first dose, adverse events (AEs) were reported in 41% of the patients (body temperature increased in 18%; headache in 13.6%; and pain in joints in 4.5%; colitis exacerbation was observed in 4.5%). After the second dose, no AEs were reported. The performed study suggests the possible efficacy and demonstrates the safety of Gam-COVID-Vac (Sputnik V) for the prophylaxis of COVID-19 in patients with PNH who experience immunosuppression due to target therapy.

Tuberculosis and COVID-19 Dually Affect Human Th17 Cell Immune Response.

COVID-19 infection not only profoundly impacts the detection of tuberculosis infection (Tbc) but also affects modality in tuberculosis patient immune response. It is important to determine immune response alterations in latent tuberculosis infection as well as in SARS-CoV-2-infected tuberculosis patients. Such changes may have underlying effects on the development and course of further tuberculosis. Here, we aimed to review the characteristics of immune response in TB patients or convalescent COVID-19 patients with latent TB infection (LTBI). MATERIALS AND METHODS: We analyzed the features of immune response in tuberculosis and COVID-19 patients. For this, we analyzed publications released from December 2019 to March 2023; those which were published in accessible international databases ("Medline", "PubMed", "Scopus") and with keywords such as "COVID-19", "SARS-CoV-2", "tuberculosis", "pulmonary tuberculosis", "latent tuberculosis infection", "Treg", "follicular Treg", and "Treg subsets", we considered. RESULTS: Through our analysis, we found that tuberculosis patients who had been infected with COVID-19 previously and elevated Th1 and Th2 cell levels. High levels of Th1 and Th2 cells may serve as a positive marker, characterizing activated immune response during TB infection. COVID-19 or post-COVID-19 subjects showed decreased Th17 levels, indicating a lack of tuberculosis development. Moreover, the typical course of tuberculosis is associated with an increase in Treg level, but COVID-19 contributes to a hyperinflammatory response. CONCLUSION: According to the data obtained, the course of tuberculosis proceeds in a dissimilar way due to the distinct immune response, elicited by SARS-CoV-2. Importantly, the development of active tuberculosis with a severe course is associated with a decline in Treg levels. Both pathogens lead to disturbed immune responses, increasing the risk of developing severe TB. The insights and findings of this paper may be used to improve the future management of individuals with latent and active tuberculosis.

Features of Myocarditis: Morphological Differential Diagnosis in Post-COVID-19 Children.

Myocarditis is characterized by dysfunction and destruction of cardiomyocytes, infiltrative inflammation, and development of fibrosis. Late diagnosis of myocarditis has been a serious global health problem, especially due to the spread of a new coronavirus infection. The aim of this review is to identify differences between myocarditis of viral etiology, including SARS-CoV-2 lesions, based on instrumental and pathomorphological findings. MATERIAL AND METHODS: We analyzed publications covering the period from December 2019 to May 2023, published in publicly accessible international databases ("Medline", "PubMed", "Scopus"), with queries for the keywords "myocarditis", "children", "cardiovascular inflammation", "COVID-19", "SARS-CoV-2", "severe acute respiratory syndrome coronavirus 2", "differential diagnosis". RESULTS: It was found that no unambiguous morphological criteria for the diagnosis of myocarditis coupled to SARS-CoV-2 lesions were identified. However, the detected histopathological changes such as virus-associated degeneration, apoptosis, cardiomyocyte necrosis, moderate interstitial hyperemia, myocardial tissue oedema, and capillary endothelial cell dysfunction were the major markers of SARS-CoV-2 infection. CONCLUSION: It is necessary further reconsider morphological criteria to diagnose SARS-CoV-2-caused myocarditis, rather than solely relying on detecting viral RNA by PCR as the sole evidence-based criterion. Similar issues accompany diagnostics of myocardial lesions associated with other viral infections. Evidence for an etiological diagnosis of myocarditis can be provided by a comprehensive analysis of the diagnostic criteria obtained, confirming virus exposure, followed by development of distinct clinical symptoms, MRI and CT changes, and morphological criteria.

New Scenarios in Heart Transplantation and Persistency of SARS-CoV-2 (Case Report).

Heart transplantation is a treatment of choice for patients with severe heart failure. Infection transmission from a donor to a recipient remains a prominent problem in organ transplantation. However, the risk of SARS-CoV-2 transmission in nonlung organ transplantation is still unclear. In this article we presented a case of a 28-year-old pregnant woman who developed heart failure soon after recovery from a SARS-CoV-2 infection in the third trimester of gestation. In the postpartum period, the heart disease worsened and the patient required cardiac transplantation. We examined the recipient's heart and made a diagnosis of left ventricular noncompaction cardiomyopathy. Immunohistochemical analysis showed SARS-CoV-2 antigen expression in the donor's heart before transplantation, and after the transplantation, an endomyocardial biopsy was taken. Moreover, an ultrastructural assessment of the endomyocardial specimen revealed endothelial and pericyte injury and a single particle on the surface of the endothelium consistent with SARS-CoV-2 viral particles. Recent findings in the literature associated these damages with SARS-CoV-2 infection. The present study describes the rare case of SARS-CoV-2 transmission from donor to postpartum recipient through a heart transplant and demonstrates the importance of endomyocardial biopsy before and after heart transplantation.

Morphological Changes in the Myocardium of Patients with Post-Acute Coronavirus Syndrome: A Study of Endomyocardial Biopsies.

The clinical manifestation study of post-acute sequelae of SARS-CoV-2 infection (PASC) has shown a lack of knowledge regarding its morphology and pathogenesis. The aim of this research was to investigate morphological manifestations of PASC in the myocardium. MATERIALS AND METHODS: The study included 38 patients requiring endomyocardial biopsy (EMB) during the post-acute phase of coronavirus infection and a control group including patients requiring EMB prior to the SARS-CoV-2 pandemic. The patients' clinical and laboratory data were analyzed. Histological examination and immunohistochemistry (IHC) of the myocardial tissue was conducted with antibodies to CD3, CD68, HLA-DR, MHC1, C1q, VP1 enteroviruses, spike protein SARS-CoV-2, Ang1, von Willebrand factor (VWF), and VEGF. The morphometric analysis included counting the mean number of inflammatory infiltrate cells per mm2 and evaluating the expression of SARS-CoV-2 spike protein, HLA-DR, MHC1, C1q, Ang1, VWF, and VEGF using a scoring system. If the expression of SARS-CoV-2 spike protein was >3 points, an additional IHC test with antibodies to ACE2, CD16 as well as RT-PCR testing of the myocardial tissue were performed. For two patients, immunofluorescence tests of the myocardial tissue were performed using antibody cocktails to SARS-CoV-2 spike protein/CD16, SARS-CoV-2 spike protein/CD68, CD80/CD163. The statistical data analysis was carried out using the Python programming language and libraries such as NumPy, SciPy, Pandas, and Matplotlib. RESULTS: The study demonstrated a significant increase in the number of CD68+ macrophages in the myocardium of PASC patients compared to patients who did not have a history of COVID-19 (p = 0.014 and p = 0.007 for patients with and without myocarditis, respectively), predominantly due to M2 macrophages. An increase in the number of CD68+ macrophages was more frequently observed in patients with shorter intervals between the most recent positive SARS-CoV-2 PCR test and the time of performing the EMB (r = -0.33 and r = -0.61 for patients with and without myocarditis, respectively). The expression scores of Ang1, VEGF, VWF, and C1q in PASC patients did not significantly differ from those in EMB samples taken before 2019. CONCLUSION: The myocardium of PASC patients demonstrated a significant increase in the number of CD68+ macrophages and a decrease in the expression of markers associated with angiopathy. No evidence of coronavirus-associated myocarditis was observed in any PASC patient.