Aim To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of “cytokine storm”. Material and methods The COLORIT study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.c., as a single dose (n=20); ruxolitinib 5 mg, twice a day (n=10); and a control group with no anti-inflammatory therapy (n=22). The effect was evaluated after 12±2 days of inpatient treatment or upon discharge, what comes first. For ethical reasons, completely randomized recruitment to the control group was not possible. Thus, for data analysis, 17 patients who did not receive any anti-inflammatory therapy for various reasons not related with inclusion into the study were added to the control group of 5 randomized patients. Inclusion criteria: presence of coronavirus pneumonia (positive PCR test for SARS-CoV-2 RNA or specific clinical presentation of pneumonia; IDC-10 codes U07.1 and U07.2); C-reactive protein (CRP) concentration >60 mg/l or its threefold increase from baseline; at least 2 of 4 symptoms (fever >37.5 °C, persistent cough, shortness of breath with inspiratory rate >20 per min or blood saturation with oxygen <94 % by the 7 th –9 th day of disease. The study primary endpoint was changes in COVID Clinical Condition Scale (CCS-COVID) score. The secondary endpoints were the dynamics of CRP and changes in the area of lung lesion according to data of computed tomography (CT) of the lungs from the date of randomization to 12±2 days. Results All three drugs significantly reduced inflammation, improved the clinical course of the disease, and decreased the disease severity as evaluated by the CCS score: in the ruxolitinib group, by 5.5 (p=0.004); in the secukinumab group, by 4 (p=0.096); in the colchicine group, by 4 (p=0.017), and in the control group, by 2 (р=0.329). In all three groups, the CCS-COVID score was 2–3 by the end of observation period, which corresponded to a mild process, while in the control group, the score was 7 (р=0.005). Time-related changes in CRP were significant in all three anti-inflammatory treatment groups with no statistical difference between the groups. By the end of the study, changes in CT of the lungs were nonsignificant. Conclusion In severe СOVID-19 with a risk of “cytokine storm”, the proactive therapy with ruxolitinib, colchicine, and secukinumab significantly reduces the inflammation severity, prevents the disease progression, and results in clinical improvement.

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Academy of Medical Sciences of Ukraine Background Identifying reliable biomarkers of early ageing is an important goal for the prevention of cardiovascular disease (CVD). Chronological age (CA) is an essential risk factor for age-related disease including CVD. Biological age (BA) may be a more accurate metric for the risk of CVD and prediction of early vascular ageing, atherosclerosis. Available data allow us to judge the relationship of early ageing with all-cause mortality, healthspan and CVD. There is a hypothesis that BA can be used into models of risk prediction and stratification of CVD for personalized treatment. Purpose to determine the relationship between BA and factors of risk CVD in patients of different ages without clinical manifestations CVD. Methods We selected 102 patients aged 31–60 years with moderate cardiovascular risk without clinical symptoms of CVD. The patients did not receive regular drug therapy. Consenting subjects had a physical assessment, anthropometric measurements, electrocardiogram recording, blood sampling for laboratory analyses, including analysis of telomerase activity, telomere length in leukocytes and buccal epithelium by a polymerase chain reaction in real-time. The SCORE scale was used for evaluation of the 10-year risk of fatal stroke and fatal myocardial infarction. In addition, 40 control individuals aged 31–60 years (20 men and 20 women), were also included in the study. BA was determined by 3 methods: PhenoAge, Voitenko’s method and Gorelkin-Pinhasov’s method. Multiple logistic regression analysis was used to develop a prediction of the early ageing model. Results The comparing patients of the control and main groups of the same CA shows, that patients with CVD risk have significantly higher BA, higher levels of proatherogenic lipids and shorter telomere length of the buccal epithelium. It was determined that body mass index, blood pressure, glucose levels are associated with an increase in BA in the main and the control groups. The increase of BA in the control group was associated with smoking, telomere length and telomerase activity and the level of antioxidant protection, in patients of the main group premature aging was associated with impaired lipid metabolism. Conclusion The biomarkers of biological aging can have benefits of the early identification of persons who age "faster" than others. The possibility of measuring biological aging can allow the assessment of health status at a time when there are still no symptoms, and interventions are more likely to be effective.

Background and Aims: Leukocyte telomere length (LTL) is a putative biological marker of early ageing, and there are demonstrated associations between LTL and cardiovascular disease (CVD). This may be partly due to the relationship of LTL with other biomarkers associated with cardiovascular disease risk (CVR). Aims: to determine age differences in the association between LTL and CVR.

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19.Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days.Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group.Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.

Background and Aims: HDL exerts several protective effects on endothelial cells including promotion of nitric oxide production and inhibition of leukocyte adhesion. It is controversial whether they depend on the interaction with scavenger receptor B1 (SR-B1) and/or sphingosine-1-phosphate receptors S1P1 and S1P3. We therefore investigated the mutual effects of SR-BI, S1P1, and S1P3 on their mRNA and protein expression as well as cellular HDL association.

The article presents the analysis of the relationship between thyroid function abnormality -subclinical hypothyroidism (SH) and non-alcoholic fatty liver disease (NAFLD), depending on age peculiarities (>50 years and <50 years), and the risk of cardiovascular complications in this category of patients. Research of early predictors of cardiovascular complications: dyslipidemia, insulin resistance, inflammatory marker- C-reactive protein, marker of vascular aging-telomerase activity and marker of endothelial dysfunction (ED) - CDECs and VEGF-A that have been analyzed are on the front burner. In this regard, the effect of the given values on the formation of cardiac risk in patients with NAFLD combined with SH was studied. 74 patients (29 men (39.2%) and 45 women (60.8%)), with verified NAFLD and SH have been examined. Patients were divided into two clinical groups: group 1 (n=31) - patients with NAFLD, with the mean age 47.2±2.6 years; group 2 (n=43) patients with NAFLD in combination with SH, with the mean age 56,8±6,5 years. Results of the performed tests have shown that patients with NAFLD combined with SH aged over 50 years have pro-atherogenic lipid profile and significantly more pronounced manifestations of endothelial dysfunction. The process of age-dependent shortening of telomere length predominantly in the buccal epithelium is an important point to be made. Consequently, the total effect of cardiometabolic risk factors in patients with NAFLD combined with SH probably is the determining factor of the rate of progression of vascular aging.