Search Results (53)

Severe fever with thrombocytopenia syndrome (SFTS) is a newly discovered tick-borne disease caused by SFTS virus (SFTSV) infection. Patients present with high fever, thrombocytopenia, and multiple organ dysfunction, with a high mortality rate and a lack of specific treatment, all of which indicate that research on the deterioration mechanism and treatment of this disease is urgent. Currently, multiple studies have indicated that cytokine storm is one of the core factors contributing to the deterioration of the disease. SFTSV inhibits the host’s type I interferon response through its non-structural protein NSs, thereby promoting immune evasion and viral replication. Extensive viral stimulation leads to dysfunction and abnormal polarization of immune cells (including monocytes, macrophages, dendritic cells, T cells, and B cells), triggering the massive release of pro-inflammatory factors(such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β)), anti-inflammatory factors (such as interleukin-10 (IL-10)), and chemokines(such as interferon-gamma inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8)). This cytokine storm exacerbates the imbalance between pro-inflammatory and anti-inflammatory factors, as well as immune paralysis, leading to vascular endothelial damage, microthrombosis, and ultimately, multi-organ failure, which determines the clinical outcome. Simultaneously, specific cytokines and immune cell phenotypes can serve as biomarkers for disease severity and prognosis. In terms of treatment, this article further summarizes the intervention strategies targeting the aforementioned immune links, including intravenous immunoglobulin (IVIG), tocilizumab (targeting the IL-6 receptor), inhibitors of Janus kinase (JAK) and nuclear factor-kappa B (NF-κB) signaling pathways, interferon, neutralizing antibodies, and other immunotherapy methods. By analyzing the dynamic changes and mechanisms of cytokine storm in the course of SFTS, and summarizing current potential immunotherapy methods, this article aims to provide a theoretical framework for the future treatment of SFTS. Full article

Myocardial and vascular injury secondary to SARS-CoV-2 infection and vaccination has emerged as a clinically relevant phenomenon, with distinct but overlapping mechanisms. Myocardial injury in COVID-19 results from a complex interplay between direct viral effects and immune-mediated inflammation, supported by histopathological studies revealing macrophage-rich infiltrates, microthrombosis, and supporting fibrosis in isolated areas. In contrast, vaccine-associated myocarditis—reported predominantly following mRNA vaccines—has a self-limiting clinical course, with mechanisms likely involving molecular mimicry, aberrant immune activation, or hypersensitivity reactions, although these pathways require further validation. Although mRNA vaccines have been associated with a small increase in myocarditis, particularly in young men, the risk is significantly lower than that associated with COVID-19 infection, and the cardiovascular benefits of vaccination far outweigh these rare adverse events in most populations. After the end of the pandemic, the number of patients with severe forms of COVID-19 has decreased significantly, but we consider that cardiac involvement remains an important issue for the acute and long-term prognosis of patients with SARS-CoV-2 infection. Our paper synthesizes the latest epidemiological and mechanistic evidence on the link between COVID-19, vaccination, and myocardial and/or vascular injuries, highlighting the clinical implications and providing practical recommendations for management, as well as future perspectives on risk assessment, targeted immunotherapy, advanced diagnostic tools, and long-term monitoring. Full article

Background: Aging exerts a progressive and multifaceted impact on the microcirculatory system, undermining the structural and molecular integrity that sustains endothelial stability across both peripheral and cerebral vascular territories. A sustained shift toward oxidative imbalance, chronic low-grade inflammation, and progressive endothelial exhaustion converges to destabilize microvascular networks, linking peripheral artery disease (PAD) with heightened susceptibility to cerebral microvascular dysfunction and neurovascular decline. As redox homeostasis deteriorates, endothelial cells progressively lose barrier-selective properties, intercellular communication with pericytes weakens, and pro-thrombotic tendencies subtly emerge, creating a permissive environment for early neurovascular injury and impaired cerebrovascular resilience. Methods: This narrative review integrates mechanistic evidence derived from experimental, clinical, and translational studies examining the interplay between oxidative stress, inflammatory signaling cascades, endothelial senescence, and blood–brain barrier (BBB) disruption across peripheral and cerebral microvascular systems. A comparative framework was applied to PAD and cerebral microcirculatory pathology to identify convergent molecular drivers and systemic mechanisms underlying endothelial deterioration. Results: Accumulating evidence demonstrates that oxidative stress disrupts endothelial mitochondrial function, compromises tight junction architecture, and accelerates angiogenic failure. Concurrent inflammatory activation amplifies these alterations through cytokine-mediated endothelial activation, enhanced leukocyte adhesion, and promotion of a pro-thrombotic microenvironment. Progressive endothelial senescence consolidates these insults into a persistent state of microvascular dysfunction characterized by diminished nitric oxide bioavailability, capillary rarefaction, and compromised barrier integrity. Notably, these pathological features are shared between PAD and the aging cerebral circulation, reinforcing the concept of a unified systemic microvascular aging phenotype. Conclusions: Microvascular failure in the aging brain should be understood as an extension of systemic endothelial deterioration driven by oxidative stress, chronic inflammation, and senescence-associated vascular exhaustion. Recognizing the shared molecular architecture linking peripheral and cerebral microcirculatory dysfunction offers a strategic framework for developing targeted therapeutic interventions aimed at restoring endothelial resilience, stabilizing BBB integrity, and preserving neurovascular homeostasis in aging populations. Full article

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated not only with respiratory illness but also with profound vascular and coagulation disturbances. Long COVID (LC) is characterized by persistent symptoms such as fatigue, dyspnea, cognitive impairment, and palpitations. Mechanistically, SARS-CoV-2 induces direct endothelial injury, promotes a pro-inflammatory cytokine milieu, and activates platelets, leading to immunothrombosis and impaired fibrinolysis. Consequently, patients exhibit microthrombosis, elevated plasma D-dimer, fibrinogen dysregulation, and persistent hypercoagulability. Clinically, this translates into an increased risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism, as well as arterial thrombotic events such as myocardial infarction and stroke, which may persist months after acute infection. Understanding the interplay between endothelial injury, inflammation, and coagulation is crucial for risk stratification and the development of preventive and therapeutic strategies. We conducted a systematic narrative review of the literature, including human clinical and mechanistic studies identified through PubMed, Scopus and Web of Science up to 30 September 2025. This review synthesizes current evidence on vascular complications in LC, highlighting endothelial dysfunction as a central pathophysiological nexus linking the acute phase of SARS-CoV-2 infection with chronic LC manifestations. Full article

Background: Sepsis-induced lung injury is a major clinical challenge, frequently complicated by pulmonary microthrombosis, which exacerbates disease severity and worsens prognosis. Recent studies suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in inflammatory and thrombotic processes. However, the contribution of PCSK9 to pulmonary microthrombosis in sepsis remains unclear. Methods: Adult male C57BL/6J mice were subjected to cecal ligation and puncture (CLP) to induce sepsis. Twelve hours post-CLP, mice received either recombinant PCSK9 (1 μg, i.p.) or the PCSK9 inhibitor evolocumab (10 mg/kg, i.p.). Platelet activation and pulmonary microthrombosis were assessed using hematoxylin–eosin staining, immunofluorescence, and thromboelastography. Results: Administration of PCSK9 significantly enhanced platelet activation and increased neutrophil extracellular trap (NET) formation, promoting pulmonary microthrombosis in septic mice. In contrast, administration of evolocumab effectively attenuated platelet activation, reduced NET formation, and alleviated pulmonary microthrombosis. Conclusions: PCSK9 exacerbates sepsis-induced pulmonary microthrombosis by promoting platelet activation and NET formation. Targeting PCSK9 may represent a novel therapeutic strategy for preventing thrombotic complications in sepsis-induced lung injury. Full article

Traumatic brain injury (TBI) is a major global health concern and a leading cause of long-term disability and mortality. While the primary mechanical insult is often the focus of acute care, secondary injury mechanisms—particularly cerebrovascular dysfunction—play a critical role in ongoing neural damage and poor outcomes. Increasing research highlights the role of neurovascular changes in TBI pathophysiology. This narrative review compiles evidence from the past decade on mechanisms, diagnostic methods, and treatments related to cerebrovascular dysfunction after TBI. A structured search of PubMed and Embase identified relevant clinical and preclinical studies. Key mechanisms include blood–brain barrier disruption, impaired cerebral autoregulation, microthrombosis, and oxidative stress. Diagnostic tools discussed include perfusion imaging, cerebrovascular reactivity testing, and blood-based biomarkers of vascular injury. Therapeutic strategies targeting the neurovascular unit are categorized by mechanism: anti-inflammatory agents (e.g., celecoxib, minocycline), mitochondrial protectors (e.g., Tanshinone IIA), and vasomodulators (e.g., sildenafil). We propose an integrated therapeutic approach for a multimodal treatment plan that integrates these interventions. The findings emphasize the importance of patient-specific vascular therapies to reduce secondary ischemic injury and enhance neurological recovery. Although promising preclinical data exist, clinical application remains limited. More well-designed trials are needed to confirm the safety and effectiveness of emerging therapies. Full article

Background: Fibrinolytic impairment is one of the key factors involved in the pathogenesis of hemostasis disturbances in sepsis, significantly contributing to microthrombosis, organ dysfunction, and mortality rates. While hemostatic assessment in sepsis typically focuses on coagulation activation, evaluating fibrinolytic activity remains challenging due to methodological limitations and a lack of standardization of the currently available methods. Objectives: This comprehensive review examines current methods for assessing fibrinolytic activity in bacterial sepsis, their clinical applications, strengths and limitations, and future perspectives for improved diagnostic approaches. Methods: We conducted a systematic literature search and identified 52 studies that investigated fibrinolysis assessment in adult patients with bacterial sepsis using biomarkers or global tests. Studies included mainly observational cohorts examining various fibrinolytic assessment methods. Results: Fibrinolytic shutdown, primarily mediated by the overproduction of plasminogen activator inhibitor-1 (PAI-1), occurs early in sepsis and correlates with disease severity and mortality. Current assessment methods include plasma biomarker measurements (PAI-1, plasmin-antiplasmin complexes, D-dimer), global plasma-based tests (clot lysis time, plasmin generation assays), and whole-blood viscoelastic testing (rotational thromboelastometry, ROTEM; thromboelastography, TEG). Modified viscoelastic tests incorporating tissue plasminogen activators demonstrate enhanced sensitivity for detecting fibrinolytic resistance. Despite efforts, standardization is still limited, and routine clinical implementation has not been achieved yet. Conclusions: Fibrinolytic assessment provides important prognostic information in sepsis, despite methodological challenges. The integration of point-of-care viscoelastic testing with modified protocols shows promise for real-time evaluation. Future research should focus on developing standardized, automated assays suitable for routine clinical practice, enabling personalized therapeutic interventions that target fibrinolytic dysfunction in sepsis. Full article

Background: COVID-19-associated coagulopathy (CAC) is a complex condition, with high rates of thrombosis, high levels of inflammation markers and hypercoagulation (increased levels of fibrinogen and D-Dimer), as well as extensive microthrombosis in the lungs and other organs of the deceased. It resembles, without being identical, other coagulation disorders such as sepsis-DIC (SIC/DIC), hemophagocyte syndrome (HPS) and thrombotic microangiopathy (TMA). Platelets (PLTs), key regulators of thrombosis, inflammation and immunity, are considered an important risk mediator in COVID-19 pathogenesis. Platelet index MPV/PLT ratio is reported in the literature as more specific in the prognosis of platelet-related systemic thrombogenicity. Studies of MPV/PLT ratio with regards to the severity of COVID-19 disease are limited, and there are no references regarding this ratio to the outcome of COVID-19 disease at specific time points of hospitalization. The aim of this study is to evaluate the relationship of COVID-19 mortality with the red cell distribution width–coefficient of variation (RDW-CV), platelets and MPV/PLT ratio parameters. Methods: Values of these parameters in 511 COVID-19 hospitalized patients were recorded (a) on admission, (b) as mean values of the 1st and 2nd week of hospitalization, (c) over the total duration of hospitalization, (d) as nadir and zenith values, and (e) at discharge. Results: As for mortality (survivors vs. deceased), statistical analysis with ROC curves showed that regarding the values of the parameters on admission, only the RDW-CV baseline was of prognostic value. Platelet parameters, absolute number and MPV/PLT ratio had predictive potential for the disease outcome only as 2nd week values. On the contrary, with regards to disease severity (mild/moderate versus severe/critical), only the MPV/PLT ratio on admission can be used for prognosis, and to a moderate degree. On multivariable logistic regression analysis, only the RDW-CV mean hospitalization value (RDW-CV mean) was an independent and prognostic variable for mortality. Regarding disease severity, the MPV/PLT ratio on admission and RDW-CV mean were independent and prognostic variables. Conclusions: RDW-CV, platelets and MPV/PLT ratio hematological parameters could be of predictive value for mortality and severity in COVID-19 disease, depending on the hospitalization timeline. Full article

Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute lung injury seen in patients. In this study, we describe the predominance of the innate immune response in hamsters inoculated with four different SARS-CoV-2 variants, underscoring phenotypic differences among them. Severe inflammatory lung injury was chronologically associated with acute and significant weight loss, mainly in animals inoculated with A.2 and Delta variants. Omicron-infected animals had lower overall histopathology scores compared to other variants. We highlight the central role of endothelial injury and activation in the pathogenesis of experimental SARS-CoV-2 infection in hamsters, characterised by the presence of proliferative type I and type II pneumocytes with abundant surfactant expression, thereby maintaining hyperinflated alveolar fields. Additionally, there was evidence of intrapulmonary lymphatic vessel proliferation, which was accompanied by a lack of detectable microthrombosis in the lung parenchyma. However, white microthrombi were observed in lymphatic vessels. Our findings suggest that the physiological compensatory mechanisms that maintain respiratory homeostasis in Golden Syrian hamsters prevent severe respiratory distress and death after SARS-CoV-2 infection. Full article

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis and obstetric complications, driven by antiphospholipid antibodies (APLAs). This review synthesizes the latest advancements and current understanding, diagnosis, and treatment of APS. APLAs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2-glycoprotein I (aβ2-GPI), interfere with coagulation and endothelial function, as well as with placental health. APS can be primary or secondary; it is often associated with systemic autoimmune diseases like lupus. The pathogenesis of APS remains only partially understood. APLAs promote thrombosis through endothelial damage, platelet activation, and inflammatory signaling pathways. Laboratory diagnosis relies on persistent positivity for APLAs and LAC through tests like ELISA and clotting assays, following a three-step confirmation process. New integrated test systems have been introduced to improve standardization. Classification criteria have evolved, with the 2023 EULAR-ACR criteria providing a weighted, domain-based scoring system, enhancing diagnostic precision. Catastrophic APS (CAPS) is a severe, rare manifestation of APS, characterized by multi-organ failure due to rapid, widespread microthrombosis and systemic inflammation, which requires urgent anticoagulation. Seronegative APS is proposed for patients with clinical features of APS but negative standard antibody tests, possibly due to non-criteria antibodies or transient immunosuppression. Treatment primarily involves long-term anticoagulation with vitamin K antagonists; direct oral anticoagulants are generally not recommended. APS diagnosis and management remain complex due to clinical heterogeneity and laboratory challenges. Continued refinement of diagnostic tools and criteria is essential for improving outcomes in this life-threatening condition. Full article

Cognitive dysfunction represents one of the most persistent and disabling features of Long COVID, yet its molecular underpinnings remain incompletely understood. This narrative review synthesizes current evidence on the pathophysiological mechanisms linking SARS-CoV-2 infection to long-term neurocognitive sequelae. Key processes include persistent neuroinflammation, blood–brain barrier (BBB) disruption, endothelial dysfunction, immune dysregulation, and neuroendocrine imbalance. Microglial activation and cytokine release (e.g., IL-6, TNF-α) promote synaptic dysfunction and neuronal injury, while activation of inflammasomes such as NLRP3 amplifies CNS inflammation. Vascular abnormalities, including microthrombosis and BBB leakage, facilitate the infiltration of peripheral immune cells and neurotoxic mediators. Hypothalamic–pituitary–adrenal axis dysfunction and reduced vagal tone further exacerbate systemic inflammation and autonomic imbalance. Biomarkers such as GFAP, NFL, IL-6, and S100B have been associated with both neuroinflammation and cognitive symptoms. Notably, transcriptomic signatures in Long COVID overlap with those observed in Alzheimer’s disease, highlighting shared pathways involving tau dysregulation, oxidative stress, and glial reactivity. Understanding these mechanisms is critical for identifying at-risk individuals and developing targeted therapeutic strategies. This review underscores the need for longitudinal research and integrative biomarker analysis to elucidate the molecular trajectory of cognitive impairment in Long COVID. Full article

Background: The impact of the SARS-CoV-2 viral infection during pregnancy on the fetus can be direct—transmitted through the placenta—and indirect—creating unfavorable conditions for the development of the fetus because of inflammation, micro-thrombosis, and hypercoagulation. Our study aimed to determine the types and frequency of pathohistological changes in placental tissue in SARS-CoV-2-positive pregnant women and to examine the possible role of oxidative stress in the prognosis of the delivery and its maternal and fetal complications. Methods: This prospective clinical study included 50 pregnant women divided into two groups, SARS-CoV-2 positive (COVID-19 group) and SARS-CoV-2 negative (control group), from who we collected demographic, clinical, obstetric, biochemical and pathologic data. Data about the newborn characteristics were also collected, which included anamnestic, clinical, and biochemical data. Results: The values of the superoxide anion radical and index of lipid peroxidation were significantly different in mothers concerning the presence of the SARS-CoV-2 infection, while the levels of the nitric oxide, index of lipid peroxidation, reduced glutathione, and superoxide dismutase were significantly different in the newborns depending on the SARS-CoV-2 infection. Newborn characteristics were similar between groups except for concentrations of IgM antibody. The incidence of pathohistological changes of the FVM type in the COVID-19 group of pregnant women was 46%, while in the control group, the incidence was 18%. Conclusions: This study confirmed the significant impact of the SARS-CoV-2 viral infection on maternal and fetal biochemical parameters and oxidative stress-mediated placental dysfunction. Future studies should be performed with more participants and follow-up neonatal development. Full article

The early introduction of strict measures during the first wave of COVID-19 in Slovakia resulted in a low number of fatal cases. Most of them (27/28) were autopsied with microscopic evaluation focusing on changes in the lungs. The average age of the patients was 79. The most common microscopic finding was diffuse alveolar damage in various stages. There were statistically significant relationships between microthrombi and neutrophil count, level of C-reactive protein, and immobility. Oxygen therapy, as a factor that might cause changes typical for diffuse alveolar damage, showed statistically significant relationships with perivascular lymphocytic infiltrate, alveolar capillaritis, alveolar bleeding, and pneumocyte hyperplasia. Hyaline membranes showed a statistically significant relationship with monocyte count, and borderline statistically significant relationships with platelet count and antimalarial therapy. The level of C-reactive protein and neutrophil count seemed to be useful for predicting microthrombi formation. Interestingly, there were no statistically significant relationships between microthrombosis and anticoagulant therapy, platelet count, or level of D-dimer. Full article

Background: The term “Long COVID” is commonly used to describe persisting symptoms after acute COVID-19. Until now, proposed mechanisms for the explanation of Long COVID have not related quantitative measurements to basic laws. In this work, a common framework for the Long COVID pathophysiological mechanism is presented, based on the blood supply deprivation and the flow diffusion equation. Methods: Case–control studies with statistically significant differences between cases (post-COVID patients) and controls, from multiple tissues and geographical areas, were gathered and tabulated. Microvascular loss (ML) was quantified by vessel density reduction (VDR), foveal avascular zone enlargement (FAZE), capillary density reduction (CDR), and percentage of perfused vessel reduction (PPVR). Both ML and hemodynamic decrease (HD) were incorporated in the tissue blood supply reduction (SR) estimation. Results: ML data were found from 763 post-COVID patients with an average VDR, FAZE, CDR, and PPVR of 16%, 31%, 14%, and 21%, respectively. The average HD from 72 post-COVID patients was 37%. The estimated SR for multiple tissues with data from 634 post-COVID patients reached a sizeable 47%. This large SR creates conditions of lower mass diffusion rates, hypoxia, and undernutrition, which at a multi-tissue level, for a long time, can explain the wide variety of the Long COVID symptoms. Conclusions: Disruption of peripheral tissue blood supply by the contribution of both ML and HD is proposed here to be the principal cause of the mechanism leading to Long COVID symptoms. Full article

Patients with COVID-19 have coagulation and platelet disorders, with platelet alterations and thrombocytopenia representing negative prognostic parameters associated with severe forms of the disease and increased lethality. Methods: The aim of this study was to study the expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation. Results: A total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19+), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS-CoV-2 (−) negative lungs (COVID-19−), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1-positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of deceased patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocyte over-expression in the lung. Conclusions: Microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium, as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence. Full article