Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as “cytokine storm”, and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical. Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients’ condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2 % and 25.6 %), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline. Results The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (р=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134 mg/dl to 41.8 mg/dl (р=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (р=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (р=0.062). Following the GCS treatment, neutrophilia increased (р=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (р=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, р=0.001). Conclusion Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism.

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).

Aim Development of a novel scale for assessing medical state in patients with new coronavirus infection based on clinical and laboratory disease severity's markers, named SHOKS-COVID scale. Material and Methods Clinical Assessment Scale (SHOKS-COVID) is based on1: clinical parameters (respiratory rate, Body temperature, SpO2 need and type of ventilation support) 2: Inflammation markers (C reactive protein (CRP) and prothrombotic marker (D-dimer)) and 3: percent of lungs injury by CT. This scale was used in several clinical studies in patients with varying severity of the course of the COVID 19. SHOKS-COVID scale was also compared against some additional biomarkers and with length of hospital stay. Results In patients with severe COVID-19 (Clinical Trial WAYFARER - 34 patients), SHOKS-COVID scores were correlated with the degree of inflammation: CRP (r = 0.64; p <0.0001); the ratio lymphocytes / CRP (r = - 0.64; p <0.0001). Also, SHOKS-COVID score correlated with the D-dimer (r = 0.35; p <0.0001) and percentage lung damage on multispiral computed tomography (MSCT) - (r = 0.77, p < 0.0001) and length stay in the clinic (r = 0.57, p = 0.0009). In patients with mild course (BISQUIT Study - 103 patients), SHOKS-COVID scores had a statistically significant positive correlation with length of fever (r = 0.37; p = 0.0002) and length of stay in the clinic (r = 0.52, p <0.0001) and negatively correlated with the ratio of lymphocytes / CRP (-0.78, p <0.0001) and the level of CRP (r=0.78; p <0.0001). Patents were grouped based on severity of COVID 19 and median and interquartile range (IQR) of SHOCKS-COVID were measured in these groups. Median and IQR of SHOCKS-COVID were 2.00 [1.0-2.5] points in mild course, 4.0 points [3.0-5.0] in moderate course, 7.0 points [6.0-9.0] in moderately severe course,12.0 points [10.0-14.0] in severe course of disease and 15.0 points [14.5-15.5] in extremely severe patients. Conclusion Here we report a novel scale of COVID 19 disease progression. This scale ranges from zero in asymptomatic patients (with normal range of biomarkers and without lung damage on CT) to fifteen in extremely severe patients. The scores for SHOKS-COVID are increasing, in parallel with the deterioration of all other biomarkers of severity and prognosis in patients with new coronavirus infection. Based on the analysis carried out, we were able to determine values of SHOKS-COVID scale and levels of main clinical and laboratory markers in patients with different severity of COVID 19.

Aim To evaluate the prevalence of iron deficiency (ID) in Russian patients with heart failure (HF). Material and methods Iron metabolism variables were studied in 498 (198 women, 300 men) patients with HF. Data were evaluated at admission for HF (97 %) or during an outpatient visit (3 %). ID was determined according to the European Society of Cardiology Guidelines. Results   83.1 % of patients had ID; only 43.5 % of patients with ID had anemia. Patients with ID were older: 70.0 [63.0;79.0] vs. 66.0 years [57.0;75.2] (p=0.009). The number of patients with ID increased in parallel with the increase in HF functional class (FC). Among patients with ID, fewer people were past or current alcohol users (p=0.002), and a greater number of patients had atrial fibrillation (60.1 vs. 45.2 %, p=0.016). A multiple logistic regression showed that more severe HF (HF FC) was associated with a higher incidence of ID detection, whereas past alcohol use was associated with less pronounced ID. An increase in N-terminal pro-brain natriuretic peptide (NT-proBNP) by 100 pg/ml was associated with an increased likelihood of ID (odds ratio, 1.006, 95 % confidence interval: 1.002–1.011, p=0.0152). Conclusion   The incidence rate of HF patients is high in the Russian Federation (83.1 %). Only 43.5 % of these patients had anemia. The prevalence of ID in the study population increased with increases in HF FC and NT-proBNP.

Aim   The aim of the study was evaluation of the effect of the coenzyme Q10 (Q10) treatment on all-cause and cardiovascular mortality of patients with chronic heart failure (CHF). Q-10 increases the electron transfer in the mitochondrial respiratory chain and exerts anti-inflammatory and antioxidant effects. These effects improve the endothelial function and reduce afterload, which facilitates the heart pumping function. Patients with reduced left ventricular (LV) ejection fraction (EF) (CHFrEF) have low Q10. Material and methods Criteria of inclusion in the meta-analysis: 1) placebo-controlled studies; 2) enrollment of at least 100 patients; 3) publications after 2010, which implies an optimal basic therapy for CHF; 4) duration of at least 6 months; 5) reported cardiovascular and/or all-cause mortality; 6) using sufficient doses of Q10 (>100 mg/day). The search was performed in CENTRAL, MEDLINE, Embase, Web of Science, E-library, and ClinicalTrials.gov databases. All-cause mortality was the primary efficacy endpoint in this systematic review and the meta-analysis. The secondary endpoint was cardiovascular mortality. Meta-analysis was performed according to the Mantel-Haenszel methods. The Cochrane criterion (I2) was used for evaluation of statistical heterogeneity. The random effects model was used at I2≥50 %, whereas the fixed effects model was used at I2<50. Results Analysis of studies published from 01.01.2011 to 01.12.2021 identified 357 publications, 23 of which corresponded to the study topic, but only 6 (providing results of four randomized clinical trials, RCT) completely met the predefined criteria. The final analysis included results of managing 1139 patients (586 received Q10 and 553 received placebo). Risk of all-cause death was analyzed by data of four RCTs (1139 patients). The decrease in the risk associated with the Q10 treatment was 36 % (OR=0.64, 95 % CI 0.48–0.87, р=0.004). The heterogeneity of studies was low (Chi2=0.84; p=0.84; I2=0 %). Risk of cardiovascular mortality was analyzed by data of two RCTs (863 patients). The decrease in the risk associated with the Q10 treatment was significant, 55% (OR=0.45, 95 % CI: 0.32–0.64, р=0.00001). In this case, the data heterogeneity was also low (Chi2=0.41; p=0.52; I2=0 %). Conclusion The meta-analysis confirmed the beneficial effect of coenzyme Q10 on the prognosis of patients with CHFrEF receiving the recommended basic therapy.

The document focuses on key issues of diuretic therapy in CHF from the standpoint of current views on the pathogenesis of edema syndrome, its diagnosis, and characteristics of using diuretics in various clinical situations.