Coronavirus disease 2019 (COVID-19) is characterized by immune activation in response to viral spread, in severe cases leading to the development of cytokine storm syndrome (CSS) and increased mortality. Despite its importance in prognosis, the pathophysiological mechanisms of CSS in COVID-19 remain to be defined. Towards this goal, we analyzed cytokine profiles and their interrelation in regard to anti-cytokine treatment with tocilizumab in 98 hospitalized patients with COVID-19. We performed a multiplex measurement of 41 circulating cytokines in the plasma of patients on admission and 3–5 days after, during the follow-up. Then we analyzed the patient groups separated in two ways: according to the clusterization of their blood cytokines and based on the administration of tocilizumab therapy. Patients with and without CSS formed distinct clusters according to their cytokine concentration changes. However, the tocilizumab therapy, administered based on the standard clinical and laboratory criteria, did not fully correspond to those clusters of CSS. Furthermore, among all cytokines, IL-6, IL-1RA, IL-10, and G-CSF demonstrated the most prominent differences between patients with and without clinical endpoints, while only IL-1RA was prognostically significant in both groups of patients with and without tocilizumab therapy, decreasing in the former and increasing in the latter during the follow-up period. Thus, CSS in COVID-19, characterized by a correlated release of multiple cytokines, does not fully correspond to the standard parameters of disease severity. Analysis of the cytokine signature, including the IL-1RA level in addition to standard clinical and laboratory parameters may be useful to define the onset of a cytokine storm in COVID-19 as well as the indications for anti-cytokine therapy.

The molecular mechanisms underlying cardiovascular complications after the SARS-CoV-2 infection remain unknown. The goal of our study was to analyze the features of blood coagulation, platelet aggregation, and plasma proteomics in COVID-19 convalescents with AMI. The study included 66 AMI patients and 58 healthy volunteers. The groups were divided according to the anti-N IgG levels (AMI post-COVID (n = 44), AMI control (n = 22), control post-COVID (n = 31), and control (n = 27)). All participants underwent rotational thromboelastometry, thrombodynamics, impedance aggregometry, and blood plasma proteomics analysis. Both AMI groups of patients demonstrated higher values of clot growth rates, thrombus size and density, as well as the elevated levels of components of the complement system, proteins modifying the state of endothelium, acute-phase and procoagulant proteins. In comparison with AMI control, AMI post-COVID patients demonstrated decreased levels of proteins connected to inflammation and hemostasis (lipopolysaccharide-binding protein, C4b-binding protein alpha-chain, plasma protease C1 inhibitor, fibrinogen beta-chain, vitamin K-dependent protein S), and altered correlations between inflammation and fibrinolysis. A new finding is that AMI post-COVID patients opposite the AMI control group, are characterized by a less noticeable growth of acute-phase proteins and hemostatic markers that could be explained by prolonged immune system alteration after COVID-19.

With the progress of COVID-19 studies, it became evident that SARS-CoV-2 infection is often associated with thrombotic complications. The goal of our present study was to evaluate which component of clot formation process including endothelial function, platelets aggregation and plasma coagulation, as well as endogenous fibrinolysis in patients with COVID-19 correlates with the severity of the disease. We prospectively included 58 patients with COVID-19 and 47 healthy volunteers as a control group that we recruited before the pandemic started. It turns out that plasma coagulation with subsequent platelet aggregation, but not endothelial function, correlates with the severity of the COVID-19. IL-6 blockade may play a beneficial role in COVID-19 induced coagulopathy.

Thrombin is a key regulator of the homeostasis system. Also, it actively participates in progression of various systemic diseases, including atherosclerosis. There is a large amount of experimental and clinical data on the involvement of thrombin in the pathogenesis of ischemic heart disease (IHD). Thus, studying thrombin activity regulation is promising. Also, the question whether it is possible to use biomarkers of thrombin activity as predictors of cardiovascular complications in IHD patients is relevant. The present review focuses on major mechanisms of thrombin functioning, its role in development and progression of atherosclerosis, and available tests for evaluation of thrombin functional activity. Major clinical studies are discussed that evaluated the efficacy of thrombin inhibitors and protease-activated receptor antagonists.

Introduction: Critically ill COVID-19 patients receiving prophylactic-dose antico-agulation exhibit high rates of thrombosis and mortality. Escalation of anticoagu-lation also does not reduce mortality and has an uncertain impact on the throm-bosis rates. The reasons why escalated doses fail to outperform prophylactic doses in reducing risks of thrombosis and death in critically ill COVID-19 patients remain unclear. We hypothesized that escalated anticoagulation would not ef-fectively prevent plasma hypercoagulability and, consequently, would not reduce the risk of thrombosis and death in some patients. Methods: We conducted a prospective multicenter study that enrolled 3860 COVID-19 patients, including 1654 critically ill. They received different doses of low-molecular-weight or unfractionated heparin, and their plasma coagulability was monitored with activated partial thromboplastin time, D-dimer, and Throm-bodynamics. A primary outcome was plasma hypercoagulability detected by Thrombodynamics. Blood samples were collected at the trough level of antico-agulation. Results: We found that escalated anticoagulation did not prevent hypercoagula-bility in 28.3% of critically ill patients at the trough level of the pharmacological activity. Critically ill patients with hypercoagulability not suppressed by anticoag-ulants had higher levels of inflammation markers and better creatinine clearance compared to critically ill patients without such hypercoagulability. Hypercoagu-lability detected by Thrombodynamics was associated with a 1.75-fold higher hazard rate for death and a 3.19-fold higher hazard rate for thrombosis. Elevated D-dimer levels were also associated with higher hazard rates for thrombosis and death, while shortened APTT were not. Simultaneous use of Thrombodynamics and D-dimer data enhanced the accuracy for predicting thrombotic events and fatal outcomes in critically ill patients. Conclusions: Thrombodynamics reliably detected hypercoagulability in COVID-19 patients and can be used in conjunction with D-dimer to assess the risk of thrombosis and death in critically ill patients. Pharmacological effect of LMWH at the trough level might be too low to prevent thrombosis in some critically ill pa-tients with severe inflammation and better creatinine clearance even if escalated doses are used.

Aim . Based on a single-center clinical experience, to evaluate the procedural features and outcomes of ultrasound-assisted catheter-directed thrombolysis using the EkoSonic system (EKOS, Boston Scientific, USA) in patients with pulmonary embolism (PE), primarily intermediate-high and high-risk. Material and methods . We retrospectively analyzed a total of 19 patients with PE hospitalized at the Davydovsky City Clinical Hospital (Moscow) in 2025-2026. They underwent ultrasound-assisted catheter-directed thrombolysis using the EKOS system. The diagnosis of PE was confirmed using multislice computed tomography pulmonary angiography. There were following inclusion criteria: Pulmonary Embolism Severity Index (PESI) score ≥III and/or a Simplified Pulmonary Embolism Severity Index (sPESI) score ≥1, combined with right ventricular dysfunction and elevated cardiac biomarkers. Treatment efficacy was determined by changes in clinical and echocardiographic parameters. Safety was assessed by the incidence of bleeding events, recurrent PE, and in-hospital mortality. Results . Ultrasound-assisted catheter-directed thrombolysis resulted in a significant reduction in right heart overload in all patients. Right ventricle to left ventricle basal diameter ratio decreased from 1,1±0,2 to 0,9±0,1 (p=0,001), pulmonary artery systolic pressure — from 56,9±9,8 to 42,4±9,1 mm Hg (p<0,001), right ventricle basal diameter — from 46,2±6,6 to 40,8±4,6 mm (p<0,001). Along with the echocardiographic changes, an improvement in the clinical condition of patients was observed with a mMRC dyspnea score decrease from 3,0 [3,0; 3,5] to 1,0 [1,0; 2,0] (p<0,001). The duration of ultrasound-assisted catheter-directed thrombolysis was 8,0 [8,0; 8,0] h with a total alteplase dose of 15,5±3,9 mg. During the hospital stay, no deaths, recurrent PE, or major or clinically significant minor bleeding events were recorded. Conclusion . The experience demonstrates the EKOS system safety in selected patients with PE, primarily at intermediate-high and high risk, and allows us to highlight key aspects of patient selection, procedure implementation, and perioperative management.