Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7–9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later.Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.Material and Methods Initially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient’s clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1].Results The median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge.Conclusions Colchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.

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.

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Background — Acute kidney injury (AKI) reaches 29% in the intensive care unit (ICU). Our study aimed to determine the prevalence, features, and the main AKI factors in critically ill patients with coronavirus disease 2019 (COVID-19). Material and Methods — The study included 37 patients with COVID-19. We analyzed the total blood count test results, biochemical profile panel, coagulation tests, and urine samples. We finally estimated the markers of kidney damage and mortality. Result — All patients in ICU had proteinuria, and 80.5% of patients had hematuria. AKI was observed in 45.9% of patients. Independent risk factors were age more than 60 years, increased C-reactive protein (CRP) level, and decreased platelet count. Conclusion — Kidney damage was observed in most critically ill patients with COVID-19. The independent risk factors for AKI in critically ill patients were elderly age, a cytokine response with a high CRP level.

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Background Secondary Antiphospholipid Syndrome (APS) can develop in 20-30% of patients with Systemic Lupus Erythematosus (SLE). Renal damage in the form of Lupus nephritis (LN) develops in 50-70% of SLE patients. Thrombotic microangiopathy (TMA) in patients with APS adds to the renal damage. It is known that risk of thrombotic complications increases when defects in genes affecting haemostasis are present. Objectives To study prognostic role of the PAI-1 (4G/5G 675), Factor XIII (G485T), FBG G (-455)A), GPIa (C807T), GPIIIa (T196C), p22phox (C242T), eNOS (G894T), MTHFR (C677T) thrombophilia genes polymorphisms in development of clinical and laboratory manifestations of APS and LN in patients with SLE and APS. Methods The study involved 100 SLE patients of Caucasian race, 80 (80%) of which were females and 20 (20%) were males in the age from 16 to 73 years. Polymorphisms were analysed with molecular genetic analysis methods. SLE was diagnosed according to American College of Rheumatology's criteria. APS was diagnosed using clinical and laboratory criteria developed in 2006. Patients groups (comparable in age and sex) were as follows: first group of 50 patients with SLE and APS, and second group of 50 patients with SLE without APS. Frequency of allelic variations of studied genes were compared between groups. Analysis of frequency of clinical manifestations of APS and LN was performed taking patients' genotypes into account. Results When comparing patients with SLE with APS and SLE without APS statistically significant differences were not observed. Patients with APS-associated arterial and/or venous thromboses more frequently have minor allele (T) and genotype (TT) p22phox (C242T) compared to patients with APS without thromboses; T: 64.5% vs 34% (p=0.033), TT: 36% vs 7% (p=0.021, OR=2.1 (95% confidence interval (CI) 1.5-22.7). Patients with livedo reticularis and APS more frequently had minor allele (T) and genotype (TT) eNOS (G894T) compared to patients without livedo; T: 33% vs 10% (p=0.019), TT: 15% vs 0% (p=0.031, OR=2.49 (95% CI 1.2-28.9). Patients with APS and rapidly progressive lupus nephritis (RPLN) considerably more frequently had minor allele (T) and genotype (TT) MTHFR (C677T); T: 45% vs 27% (p=0.038), TT: 30% vs 0% (p=0.033, OR=3.1 (95% CI 1.4-32.7). In the group of patients without APS no correlation between studied polymorphisms and renal damage was found. Conclusions Having mutant allele of p22phox (C242T) subunit of NADPH-oxidase increases risk of developing arterial and venous thromboses in patients with SLE and APS. eNOS (G894T) gene polymorphism is associated with higher frequency of blood microcirculation disorders in organs and tissues of patients with SLE and APS. RPLN development risk in patients with SLE is probably related to mutation in MTHFR gene (C677T). Allelic contribution of PAI-1 (4G/5G 675), Factor XIII (G485T), FBG (G (-455)A), GPIa (C807T) and GPIIIa (T196C) is less pronounced in development of thrombotic complications within SLE with APS, probably because of existence ...

Anti-angiogenic anticancer drugs that block vascular endothelial growth factor (VEGF) can cause kidney damage. An early assessment of the risk of nephrotoxicity would allow the development of optimal treatment approaches and allow for relatively safer therapeutic regimens. The aim of this study was to assess the utility of neutrophilic gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), hypoxia inducible factor-1α (HIF-1α) and nephrin levels in urine as early biomarkers for the nephrotoxicity of anti-VEGF drugs. The study included 50 patients who received anti-VEGF drugs (aflibercept, bevacizumab or ramucirumab) for 8 weeks. The levels of KIM-1, NGAL, HIF-1α and nephrin in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity, a logistic regression analysis was performed with the inclusion of the primary clinical and laboratory parameters. The primary outcome measure was a decrease in glomerular filtration rate (GFR) to <60 ml/min/1.73 m 2 at 8 weeks, and nephrotoxicity resulting in discontinuation within 9 months. The primary outcome goal was achieved in 21 (42%) patients treated with anti-VEGF drugs. Increased NGAL, KIM-1, HIF-1α and nephrin levels in urine at 1 week of treatment predicted the development of nephrotoxicity. High sensitivity and specificity of these urinary biomarkers were established by ROC analysis: KIM-1 [area under the curve (AUC) 0.69], NGAL (AUC 0.7), HIF-1α (AUC 0.7) and nephrin (AUC 0.7). The unfavorable predictors of nephrotoxicity were an initial decrease in estimated GFR, a history of arterial hypertension, and an increase in urinary concentration KIM-1 OR of 1.1 [CI 95% 1.02-1.183], and HIF-1α OR of 5.6 [CI 95% 3.601-8.949] (P<0,05) at 1 and 2 weeks of treatment. Urinary NGAL, KIM-1, HIF-1α and nephrin are early biomarkers of nephrotoxicity following treatment with anti-VEGF anticancer drugs. The independent risk factors for nephrotoxicity are the initial decrease in GFR, arterial hypertension, and an increase in the concentration of KIM-1 and HIF-1α in the urine in the early stages of therapy.

Среди факторов хозяина, определяющих естествен-ное течение хронической инфекции, вызванной вирусом гепатита С (HCV), и ее исход, наряду с классическими (клинико-демографическими) в последнее время широко