COVID-19 is associated with an increased risk of venous thromboembolism (VTE) in hospitalized patients. Although prior studies have attempted to identify predictors of VTE, restricted sample size and use of administrative claims data have limited such analyses. We utilized data from hospitalized patients in the CORONA-VTE Network, a United States multicenter registry of adult patients with PCR-confirmed COVID-19 (N = 3,844). The primary outcome was time-to-first event for a composite of adjudicated pulmonary embolism or deep vein thrombosis during 90-day follow-up. The candidate variables were selected by a priori clinical consensus. We conducted cause-specific Cox regression analysis adjusted for the selected variables for each imputed dataset and pooled the estimated HRs for reporting (p < 0.05 for significance). VTE occurred in 206 patients, with a cumulative incidence of 5.3% at 90 days. The covariates associated with increased risk of VTE were history of VTE (HR: 1.71; 95% CI: 1.11-2.63), corticosteroid therapy (HR: 1.76; 95% CI: 1.32-2.33) and known thrombophilia (HR: 3.56; 95% CI: 1.54-8.21) while therapeutic anticoagulation at baseline (HR: 0.42; 95% CI: 0.26-0.69), antecedent use of statins (HR: 0.67; 95% CI: 0.50-0.90), and prophylactic anticoagulation during hospitalization (HR: 0.52; 95% CI: 0.38-0.71) were associated with reduced risk of VTE. While prior VTE, corticosteroid therapy, and known thrombophilia were associated with an increased risk of VTE, prescriptions of prophylactic and therapeutic anticoagulation, and statins were associated with a decreased risk. Once externally validated, these findings may inform risk assessment in hospitalized patients with COVID-19.

SARS-CoV-2 can encode circular RNAs (circRNAs); however, the potential effects of exogenous SARS-CoV-2 circRNAs on cardiovascular sequelae remain unknown. Three circRNAs derived from the nucleocapsid (N) gene of SARS-CoV-2, namely, circSARS-CV2-Ns, were identified for functional studies. In particular, circSARS-CV2-N1368 was shown to enhance platelet adhesiveness to endothelial cells (ECs) and inhibit EC-dependent vascular relaxation. Moreover, exogenous expression of circSARS-CV2-N1368 suppressed EC proliferation and migration and decreased angiogenesis and cardiac organoid beating. Mechanistically, we elucidated that circSARS-CV2-N1368 sponged the microRNA miR-103a-3p, which could reverse circSARS-CV2-N1368-induced EC damage. Additionally, activating transcription factor 7 (ATF7) was identified as a target gene of miR-103a-3p, and Toll-like receptor 4 (TLR4) was verified as a downstream gene of ATF7 that mediates circARS-CV2-N1368-induced activation of nuclear factor kappa B (NF-κB) signaling and ROS production in ECs. Importantly, the reactive oxygen species (ROS) scavenger NAC mitigated the circSARS-CV2-N1368-promoted EC impairment. Our findings reveal that the TLR4/NF-κB/ROS signal pathway is critical for mediating circSARS-CV2-N1368-promoted oxidative damage in ECs, providing insights into the endothelial impairment caused by circSARS-CV2-Ns.

Limited knowledge exists about prophylactic anticoagulation patterns in patients hospitalized for COVID-19.

We conducted a retrospective cohort study using American Heart Association COVID-19 Cardiovascular Disease Registry data from May 2020 to March 2022. We included patients without preexisting indications for or contraindications to anticoagulation, excluding those with missing anticoagulation data. Patients were categorized by the highest anticoagulation dose received. Multilevel logistic regression was used to assess the relationship between anticoagulation use/dose, patient demographics, clinical presentation, in-hospital course, institutional characteristics, and admission date, accounting for hospital clustering. Among 26 775 patients, 4157 (16%) received no anticoagulation, 15 617 (58%) low-dose, 3071 (11%) intermediate-dose, and 3930 (15%) full-dose anticoagulation. Significant hospital-level variability occurred for any anticoagulation use (range, 0%-98%; P<0.0001) and by dose (full anticoagulation range, 0%-85%; P<0.0001). Controlling for hospital variability, older age, male sex, non-White race, higher body mass index, higher platelets, corticosteroid use, and intensive care unit admission were positively associated with any anticoagulation use. Older age, male sex, higher body mass index, higher platelets, corticosteroid use, intensive care unit admission, mechanical ventilation, and admission before October 2020 were associated with higher anticoagulation dose (full versus low dose). Rates of no anticoagulation significantly increased in both intensive care unit and non-intensive care unit strata over time (P trend=0.01 and <0.0001, respectively).

In this large real-world analysis, nearly 1 in 6 patients hospitalized for COVID-19 received no prophylactic anticoagulation. Patient and disease characteristics associated with thrombotic risk and COVID-19 severity correlated with anticoagulation strategy. Importantly, substantial institutional differences emerged, highlighting gaps between clinical practice and guideline recommendations.

Thromboembolic events of COVID-19 are due to hyperinflammatory process associated with hypercoagulable state. The aim of the study was to determine characteristics and clinical outcomes of patients with COVID-19 who presented with aortic thrombus.

We retrospectively conducted a single-center, descriptive study over a period of 1 year and 7 months, between June 2021 and December 2022, involving eight patients with documented SARS-CoV-2 infection associated with aortic thrombus revealed by acute limb ischemia.

The mean age of patients was 67 years with a median of 64, 5 ± 14. Of the eight included patients, six were men and two were women. Aortic thrombus was diagnosed in all cases. Six patients developed one episode of acute limb ischemia and one patient had recurrent upper and lower ischemia despite full anticoagulation whereas one patient had distal embolization with palpable pulses. In six patients, the thrombi were located in descending and abdominal aorta, while two patients presented with ascending aorta floating thrombus. Seven patients required urgent revascularization whereas medical treatment was recommended for one patient. The primary outcomes were successful in five cases, one patient had to be amputated above elbow, whereas two patients died due to a rapid deterioration of respiratory condition.

Aortic thrombosis is a rare clinical presentation in SARS-CoV-2 infection but with potentially fatal embolic complication. Physicians should maintain a high degree of clinical suspicion to diagnose thromboembolic consequences of SARS-CoV-2 infection for timely management and avoiding morbidities like ischemic stroke and major amputations.

Coronavirus disease 2019 (COVID-19) is a strong risk factor for venous thromboembolism (VTE). Few studies have evaluated the effectiveness of COVID-19 vaccination in preventing hospitalization for COVID-19 with VTE.

Adults hospitalized at 21 sites between March 2021 and October 2022 with symptoms of acute respiratory illness were assessed for COVID-19, completion of the original monovalent messenger RNA (mRNA) COVID-19 vaccination series, and VTE. Prevalence of VTE was compared between unvaccinated and vaccinated patients with COVID-19. The vaccine effectiveness (VE) in preventing COVID-19 hospitalization with VTE was calculated using a test-negative design. The VE was also stratified by predominant circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant.

Among 18 811 patients (median age [interquartile range], 63 [50-73] years; 49% women; 59% non-Hispanic white, 20% non-Hispanic black, and 14% Hispanic; and median of 2 comorbid conditions [interquartile range, 1-3]), 9792 were admitted with COVID-19 (44% vaccinated), and 9019 were test-negative controls (73% vaccinated). Among patients with COVID-19, 601 had VTE diagnosed by hospital day 28, of whom 170 were vaccinated. VTE was more common among unvaccinated than vaccinated patients with COVID-19 (7.8% vs 4.0%; P = .001). The VE against COVID-19 hospitalization with VTE was 84% overall (95% confidence interval, 80%-87%), and VE stratified by predominant circulating variant was 88% (73%-95%) for Alpha, 93% (90%-95%) for Delta, and 68% (58%-76%) for Omicron variants.

Vaccination with the original monovalent mRNA series was associated with a decrease in COVID-19 hospitalization with VTE, though data detailing prior history of VTE and use of anticoagulation were not available. These findings will inform risk-benefit considerations for those considering vaccination.

Background/Objectives: To provide insight into populations at higher risk of COVID-19-related retinal vascular occlusion, we identified the baseline characteristics of COVID-19 patients and vaccine recipients who developed this condition by conducting a systematic review to summarize the findings and evaluate the current knowledge on this subject. Methods: An electronic search on the PubMed and Scopus databases was performed for relevant case reports or series regarding retinal vascular occlusion in patients with past or present COVID-19 infection or SARS-CoV-2 immunization. This study was conducted using a pre-determined protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 34 studies were enrolled in this systematic review. A total of 21 patients (14 males, 66.7%) have been diagnosed with COVID-19 related retinal vein occlusion (RVO, mean age = 41.9 ± 10.3 years), and 15 patients (12 males, 80%) have been diagnosed with retinal artery occlusion (RAO, mean age = 56.9 ± 13.2 years). The time to RVO since COVID-19 infection or SARS-CoV-2 immunization ranged from 8 h to 51 days (mean = 12.3 ± 15.7 days), while the time to RAO ranged from 2 to 40 days (mean = 14.9 ± 10.8 days). Fifteen out of the twenty-one patients (71.4%) with RVO had a significant improvement in visual acuity after the resolution of symptoms while eight out of the fifteen patients (53.3%) with RAO did not show improvement. Conclusions: COVID-19 seems to play a significant role in the pathogenesis of vascular occlusion, as it is suggested to increase the risk of thromboembolic episodes. However, the pathophysiologic mechanisms have not been fully elucidated, and further studies are expected to shed light on this phenomenon.

Studies have shown that coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Studies have yet to examine the interconnectedness between COVID-19, hypercoagulability, and socioeconomics. The aim of this work was to investigate socioeconomic factors that may be associated with pulmonary embolism (PE), deep vein thrombosis (DVT), and COVID-19 in the United States.

We performed a 1-year (2020) analysis of the National Inpatient Sample database. We identified all adult patients diagnosed with COVID-19, acute PE, or acute DVT using unweighted samples. We calculated the correlation and odds ratio (OR) between COVID-19 and (1) PE and (2) DVT. We executed a univariate analysis followed by a multivariate analysis to examine the effect of different factors on PE and DVT during the COVID-19 pandemic.

We identified 322,319 patients with COVID-19; 78,101 and 67,826 patients were identified with PE and DVT, respectively. PE and DVT, as well as inpatient mortality associated with both conditions, are significantly correlated with COVID-19. The OR between COVID-19 and PE was 2.04, while the OR between COVID-19 and DVT was 1.44. Using multivariate analysis, COVID-19 was associated with a higher incidence of PE (coefficient, 2.05) and DVT (coefficient, 1.42). Other factors that were significantly associated (P < .001) with increased incidence of PE and DVT along with their coefficients, respectively, include Black race (95% confidence interval [CI], 1.23-1.14), top quartile income (95% CI, 1.08-1.16), west region (95% CI, 1.10-1.04), urban teaching facilities (95% CI, 1.09-1.63), large bed size hospitals (95% CI, 1.08-1.29), insufficient insurance (95% CI, 1.88-2.19), hypertension (95% CI, 1.24-1.32), and obesity (95% CI, 1.41-1.25). Factors that were significantly associated (P < .001) with decreased incidence of PE and DVT along with their coefficients, respectively, include Asians/Pacific Islanders (95% CI, 0.52-0.53), female sex (95% CI, 0.79-0.74), homelessness (95% CI, 0.62-0.61), and diabetes mellitus (0.77-0.90).

In the Nationwide Inpatient Sample, COVID-19 is correlated positively with venous thromboembolism, including its subtypes, PE and DVT. Using a multivariate analysis, Black race, male sex, top quartile income, west region, urban teaching facilities, large bed size hospitals, and insufficient social insurance were associated significantly with an increased incidence of PE and DVT. Asians/Pacific Islanders, female sex, homelessness, and diabetes mellitus were significantly associated decreased incidence of PE and DVT.

Acute portomesenteric venous thrombosis (PVT) is a rare but potentially life-threatening condition in individuals without cirrhosis. Initial management typically involves anticoagulation therapy, but the optimal approach to interventional treatment remains a topic of ongoing research. This article explores both traditional and emerging endovascular techniques, providing an overview of the existing evidence supporting their use. Additionally, it delves into the significance of acute PVT in the context of contemporary pathologies, notably coronavirus disease 2019 infection, vaccine-induced immune thrombotic thrombocytopenia, and liver transplantation.

TLR4 stands at the forefront of innate immune responses, recognizing various pathogen- associated molecular patterns and endogenous ligands, thus serving as a pivotal mediator in the immune system's defense against infections and tissue damage. Beyond its canonical role in infection, emerging evidence highlights TLR4's involvement in numerous non-infectious human diseases, ranging from metabolic disorders to neurodegenerative conditions and cancer. Targeting TLR4 signaling pathways presents a promising therapeutic approach with broad applicability across these diverse pathological states. In metabolic disorders such as obesity and diabetes, dysregulated TLR4 activation contributes to chronic low-grade inflammation and insulin resistance, driving disease progression. In cardiovascular diseases, TLR4 signaling promotes vascular inflammation and atherogenesis, implicating its potential as a therapeutic target to mitigate cardiovascular risk. Neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, exhibit aberrant TLR4 activation linked to neuroinflammation and neuronal damage, suggesting TLR4 modulation as a strategy to attenuate neurodegeneration. Additionally, in cancer, TLR4 signaling within the tumor microenvironment promotes tumor progression, metastasis, and immune evasion, underscoring its relevance as a target for anticancer therapy. Advances in understanding TLR4 signaling cascades and their contributions to disease pathogenesis have spurred the development of various pharmacological agents targeting TLR4. These agents range from small molecule inhibitors to monoclonal antibodies, with some undergoing preclinical and clinical evaluations. Furthermore, strategies involving TLR4 modulation through dietary interventions and microbiota manipulation offer additional avenues for therapeutic exploration. Hence, targeting TLR4 holds significant promise as a therapeutic strategy across a spectrum of human diseases, offering the potential to modulate inflammation, restore immune homeostasis, and impede disease progression.

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.

COVID-19 disease has spread rapidly worldwide, causing high mortality. Accessible biomarkers capable of early identification of patients at risk of severe form are needed in clinical practice. The aim of the study was to determine the biological markers that predict a critical condition.

Retrospective study including patients with confirmed COVID-19 hospitalized between September 2020 and June 2021. The primary endpoint was progression to critical status within 7 days from admission. We defined two groups:Critical group: Patients who developed a critical condition or died or transferred to the ICU before or at 7 th day.Non-critical group: Patients who remained in non-critical respiratory status until 7 th day or discharged before or at 7 th day.

Our study included 456 patients, with a sex ratio of 1.32 and an average age of 62 years. At the 7 th day of hospitalization, 115 (25.2%) patients were in the critical group and 341 (74.8%) patients were in the non-critical group. The univariate logistic regression indicated that laboratory findings between non-critical and critical groups showed that C-reactive protein (CRP) (p=0.047), D-Dimer (p=0.011), creatinine (0.026), creatine kinase (p=0.039), lactate dehydrogenase (p=0.04), and troponin (p=0.001) were all higher among patients in critical group. However, lymphocyte (p<0.001) and platelet (p<0.001) counts were significantly lower among the critical group. Multivariate logistic regression model, identified four independent risk factors: lymphopenia (OR=2.771, 95%CI=1.482-5.181, p=0.001), Neutrophil to Lymphocyte Ratio (NLR) (OR=2.286, 95%CI=1.461-3.578, p<0.001), thrombocytopenia (OR=1.944, 95%CI=1.092-3.459, p=0.024), and CRP>71.5 (OR=1.598, 95% CI=1.042-2.45, p=0.032) were associated to critical group.

Our results show the predictive value of lymphopenia, thrombocytopenia, high NLR and CRP levels to evaluate the prognosis of COVID-19 pneumonia. A prognostic score could be proposed for guiding clinical care and improving patient outcomes.

Inpatient and extended postdischarge thromboprophylaxis of COVID-19 patients remains suboptimal despite antithrombotic guidelines.

To determine whether a novel electronic health record-agnostic clinical decision support (CDS) tool incorporating the International Medical Prevention Registry on Venous Thromboembolism plus D-dimer (IMPROVE-DD) venous thromboembolism (VTE) scores increases appropriate inpatient and extended postdischarge thromboprophylaxis and improves outcomes in COVID-19 inpatients.

This post hoc analysis of the IMPROVE-DD cluster randomized trial evaluated thromboprophylaxis CDS among COVID-19 inpatients at 4 New York hospitals between December 21, 2020, and January 21, 2022. Hospitals were randomized 1:1 to CDS (intervention, n = 2) vs no CDS (usual care, n = 2). The primary outcome was rate of appropriate thromboprophylaxis. Secondary outcomes included rates of major thromboembolism, all-cause and VTE-related readmissions and death, major bleeding (MB), and all-cause mortality 30 days after discharge.

Two thousand four hundred fifty-two COVID-19 inpatients were analyzed (CDS, 1355; no CDS, 1097). Mean age was 73.7 ± 9.37 years; 50.1% of participants were male. CDS adoption was 96.8% (intervention group). CDS was associated with increased appropriate at-discharge extended thromboprophylaxis (42.6% vs 28.8%; odds ratio [OR], 1.83; 95% CI, 1.39-2.41; P < .001). CDS was associated with reduced VTE (OR, 0.54; 95% CI, 0.39-0.75; P < .001), arterial thromboembolism (OR, 0.10; 95% CI, 0.01-0.81; P = .01), total thromboembolism (OR, 0.50; 95% CI, 0.36-0.69; P < .001), and 30-day all-cause readmission/death (OR, 0.78; 95% CI, 0.62-0.99; P = .04). There were no differences in MB, VTE-related readmissions/death, or all-cause mortality.

Electronic health record-agnostic CDS incorporating IMPROVE-DD VTE scores had high adoption, was associated with increased appropriate at-discharge extended thromboprophylaxis, and reduced thromboembolism and all-cause readmission/death without increasing MB in COVID-19 inpatients.

Circulating proteomes provide a snapshot of the physiological state of a human organism responding to pathogenic challenges and drug interventions. The outcomes of patients with COVID-19 and acute respiratory distress syndrome triggered by the SARS-CoV2 virus remain uncertain. Tocilizumab is an anti-interleukin-6 treatment that exerts encouraging clinical activity by controlling the cytokine storm and improving respiratory distress in patients with COVID-19. We investigate the biological determinants of therapeutic outcomes after tocilizumab treatment. Overall, 28 patients hospitalized due to severe COVID-19 who were treated with tocilizumab intravenously were included in this study. Sera were collected before and after tocilizumab, and the patient's outcome was evaluated until day 30 post-tocilizumab infusion for favorable therapeutic response to tocilizumab and mortality. Hyperreaction monitoring measurements by liquid chromatography-mass spectrometry-based proteomic analysis with data-independent acquisition quantified 510 proteins and 7019 peptides in the serum of patients. Alterations in the serum proteome reflect COVID-19 outcomes in patients treated with tocilizumab. Our results suggested that circulating proteins associated with the most significant prognostic impact belonged to the complement system, platelet degranulation, acute-phase proteins, and the Fc-epsilon receptor signaling pathway. Among these, upregulation of the complement system by activation of the classical pathway was associated with poor response to tocilizumab, and upregulation of Fc-epsilon receptor signaling was associated with lower mortality.

Factors associated with cardiovascular complications of COVID-19 remain understudied.

Here we investigate the occurrence and risk factors of arrythmias, myocardial infarction and/or stroke, and thromboembolism in the course of COVID-19.

We have performed an observational study with prospectively designed data collection. Data of patients diagnosed with COVID-19 who were admitted from March 6th 2020 to November 30th 2021 in our Hospital were analyzed. Logistic regression was used to identify variables associated with the odds of early hospital death due to COVID-19.

Fourteen-point three percent of 1964 patients had cardiovascular complications, 6.36 % arrhythmias, 5.5 % thromboembolic events and 2.39 % myocardial infarction and/or stroke. Factors independently increasing the odds of arrhythmia were older age (OR=1.49 [95 % CI: 1.17-1.92], p = 0.02), longer time between admission and the first onset of symptoms (1.02 [0.99-1.05], p = 0.049), concomitant atrial fibrillation/flutter (2.84 [1.37-5.70], p = 0.004), nicotinism (2.49 [1.37-4.49], p = 0.002), and eGFR<60 ml/min/1.73m2 (2.44 [1.08-5.59], p = 0.033). Factors independently increasing the odds of myocardial infarction and/or stroke were dementia (4.55 [0.97-19.3], p = 0.044), hemiplegia (12.67 [3.12-46.1], p < 0.001), nicotinism (3.36 [1.30-10.4], p = 0.013) and higher C-reactive protein concentration (1.01 [1.00-1.01], p = 0.040). Factors independently increasing the odds of thromboembolic events were longer hospitalization (1.08 [1.05-1.10], p < 0.001) and higher d-dimers (1.04 [1.02-1.05], <0.001).

The risk of cardiovascular complications was especially pronounced in patients with older age, pre-existing cardiovascular disease and more sever pneumonia at presentation to care. This underlines the importance of close and careful clinical follow-up in the course of COVID-19 for specific patients' populations, including a pro-active approach in diagnosis.

Despite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood.

In this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests.

The study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time.

Tocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.

Acute ischemic stroke (AIS) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to explore neurovascular imaging patterns in patients with SARS-CoV-2-related AIS.

We retrospectively analyzed clinical and radiological data of patients hospitalized with AIS and a positive PCR test for SARS-CoV-2 prior to AIS onset. The control group comprised of AIS patients from a pre-COVID-19 pandemic period matched for gender and age.

Thirty-five SARS-CoV-2-related stroke patients, and 35 controls were included. Fifty-seven percent of SARS-CoV-2 patients had either mild or asymptomatic disease. A distinctive imaging pattern of floating arterial mural thrombus was detected in 5 patients of the SARS-CoV-2 group. In 4 patients thrombus was attached to a stenotic atherosclerotic plaque in the proximal internal carotid artery. In the 5th patient a cardiac CTA showed multiple floating thrombi in the descending aorta. In the control group, floating thrombus was only detected in one patient. Treatment with dual antiplatelet therapy was associated with thrombus dissolution and good clinical outcome. Patients with floating thrombi had a longer time from SARS-CoV-2 diagnosis to stroke onset (mean 7.4 versus 3.4 days).

Floating arterial mural thrombi attached to atherosclerotic plaques are unique characteristic source of AIS in SARS-CoV-2 patients. They may lead to ischemic stroke in patients with mild or asymptomatic infection up to 1-2 weeks from SARS-CoV-2 diagnosis. Patients with embolic AIS and SARS-CoV-2 diagnosis should perform high resolution cranio-cervical vascular imaging to evaluate floating thrombi as a potential embolic source.

Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favor thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of this study was to analyze the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting activation thrombosis in COVID-19. We measured serum levels of sNOX2-dp, zonulin, LPS, D-dimer, and albumin in 175 patients with COVID-19, classified as having or not acute respiratory distress syndrome (ARDS), and 50 healthy subjects. Baseline levels of sNOX2-dp, LPS, zonulin, D-dimer, albumin, and hs-CRP were significantly higher in COVID-19 compared to controls. In COVID-19 patients with ARDS, sNOX2-dp, LPS, zonulin, D-dimer, and hs-CRP were significantly higher compared to COVID-19 patients without ARDS. Conversely, concentration of albumin was lower in patients with ARDS compared with those without ARDS and inversely associated with LPS. In the COVID-19 cohort, the number of patients with ARDS progressively increased according to sNOX2-dp and LPS quartiles; a significant correlation between LPS and sNOX2-dp and LPS and D-dimer was detected in COVID-19. In a multivariable logistic regression model, LPS/albumin levels and D-dimer predicted thrombotic events. In COVID-19 patients, LPS is significantly associated with a hypercoagulation state and disease severity. In vitro, LPS can increase endothelial oxidative stress and coagulation biomarkers that were reduced by the treatment with albumin. In conclusion, impaired gut barrier permeability, increased NOX2 activation, and low serum albumin may account for low-grade endotoxemia and may be implicated in thrombotic events in COVID-19.

During the COVID-19 pandemic, there was increased interest in the issue of thrombotic complications of acute respiratory infections. Clinical reports and pathological studies have revealed that thrombus formation in COVID-19 may involve the venous and arterial vasculature. As thrombotic complications of infectious respiratory diseases are increasingly considered in the context of COVID-19, the fact that thrombosis in lung diseases of viral and bacterial etiology was described long before the pandemic is overlooked. Pre-pandemic studies show that bacterial and viral respiratory infections are associated with an increased risk of thrombotic complications such as myocardial infarction, ischemic stroke, pulmonary embolism, and other critical illnesses caused by arterial and venous thrombosis. This narrative review article aims to summarize the current evidence regarding thrombotic complications and their pathogenesis in acute lower respiratory tract infections.

High-sensitive cardiac troponin T (hs-cTnT) assessments are routinely conducted in German emergency departments (EDs). However, data describing a large number of ED patients with pathological hs-cTnT levels and subsequent clinical outcomes are limited.

This retrospective descriptive analysis included 141.892 patients who presented to the interdisciplinary ED at Klinikum rechts der Isar in Munich, Germany, between January 2019 and December 2021. Patients with trauma diagnoses were excluded, focusing on those with elevated hs-cTnT levels. These patients were categorized into three groups based on the International Classification of Procedures in Medicine (ICPM): those with elevated hs-cTnT who received no coronary angiography (NCA), those who underwent diagnostic coronary angiography (DCA), and those who received percutaneous coronary intervention (PCI). The objective of this study was to characterize a large emergency department patient cohort and assess their subsequent clinical outcomes.

After initial Manchester Triage Sytem (MTS) categorization, 32.6% (46.307/141.892) of patients were identified as non-trauma cases. Of these, 9.9% (4.587/46.307) had hs-cTnT levels exceeding 14 ng/L. Within this subset, 70.4% (3.230/4.587) did not undergo coronary angiography, 15.4% (705/4.587) underwent DCA and 14.2% (652/4.587) received PCI. Chest pain occurred more frequently in the PCI group (28.0%, 160/652) compared to the DCA group (18.3%, 113/705) or NCA group (5.7%, 159/3230), p < 0.001. However, breathing problems occurred more frequently in the NCA group (23.2%, 647/3230) compared to the PCI group (17.7%, 101/652) or DCA group (21.8%, 135/705), p < 0.001. Also, collapse was more frequent in patients in the NCA group (4.0%, 112/3230) compared to the DCA group (3.4%, 21/705) or PCI group (3.5%, 20/652), p < 0.001. Overall, in-hospital mortality was significantly higher in the NCA group (7.9%, 256/3230) compared to the DCA group (2.3%, 16/705) or PCI group (4.1%, 27/652), p < 0.001.

Emergency patients with elevated hs-cTnT who did not undergo coronary angiography faced a higher risk of in-hospital mortality in our retrospective descriptive study. Given the heterogeneous nature of presenting complaints in emergency departments, identifying at-risk patients can pose challenges for treating physicians.

This study aims to understand the repercussions of the COVID-19 pandemic on hospitalized patients with peripheral arterial disease (PAD) in China, who did not contract SARS-CoV-2. We conducted a multicenter cross-sectional analysis comparing the characteristics and outcomes of hospitalized PAD patients across two distinct periods: Pre-pandemic (P1, from January 2018 to December 2019) and during the pandemic (P2, from January 2020 to December 2021). During P1, 762 hospitalized patients were treated, with an average age of 72.3 years, while 478 patients were treated in P2, with an average age of 65.1 years. Notably, hospitalized patients admitted during the pandemic (P2) exhibited a significantly higher incidence of chronic limb-threatening ischemia (CLTI, 70% vs 54%), diabetic foot infection (47% vs 29%), and infra-popliteal lesions (28% vs 22%). Furthermore, these patients demonstrated a marked deterioration in their Rutherford category and an increased mean score in the Wound, Ischemia, and foot Infection classification system (WIfI). Treatment during the pandemic emerged as a predictor of reduced procedural success and increased major adverse limb events. Factors such as the presence of diabetic foot infection, renal impairment, and deteriorating WIfI scores were identified as independent risk indicators for major adverse limb events. Our results demonstrate that intensive care was provided to severe cases of PAD even during the challenging circumstances of the COVID-19 pandemic. Despite the unprecedented pressures on healthcare systems, patients with severe PAD, particularly those with CLTI, continued to receive necessary in-patient care. The findings underscore the importance of timely medical interventions and extended follow-up for patients exhibiting high-risk factors.

Coronavirus disease 2019 (COVID19) can cause gastrointestinal complications as well as respiratory tract disease. Coagulation abnormalities and thrombosis frequently occur in COVID19, especially in cases with severe clinical outcome. The relationship between gastrointestinal perforation and coagulopathy due to COVID19 remains unclear.

A 49-year-old female received Chimeric antigen receptor T (CAR-T) therapy for an early recurrence of diffuse large B-cell lymphoma (DLBCL) that was refractory to chemotherapy. She was diagnosed with cytokine release syndrome (CRS) because of a fever and oxygen desaturation, and administered tocilizumab. Forty days after completing CAR-T therapy, she was infected with COVID19 and transferred to our hospital. Her general condition worsened and she developed COVID19 pneumonia, and then steroid pulse therapy was started. While her respiratory condition improved, she experienced pain in the anal region and computed tomography (CT) revealed a rectal perforation. An emergency surgery was undertaken, and the lower rectum wall was found to be completely necrotic. Removal of the necrotic part of the rectum tissue, and drainage and lavage of necrotic tissue in the pelvic cavity were performed. The remaining rectum was resected with partial sigmoidectomy, but we could not make the anal stump closed. In addition, an end colostomy in the sigmoid colon was performed. Histopathological findings showed thromboses in the rectal mesentery veins. After the first surgery, the pelvic abscess cavity persisted and her high-grade fever continued. Reoperation was laparoscopically performed, and she underwent a resection of anal canal with residual necrotic rectal and mesorectal tissue, and a drainage of the pelvic abscess. After the reoperation, her general condition improved and CT showed that the abscess cavity had significantly improved.

Gastrointestinal perforation, especially rectal necrosis due to coagulopathy caused by severe COVID19 infection, is a rare but life-threatening complication. Physicians should have a high degree of clinical suspicion for timely diagnosis and management, and surgical intervention is necessary in cases of rectal necrosis.

Following the acute phase of SARS-CoV-2 infection, certain individuals experience persistent symptoms referred to as long COVID. This study analyzed the patients categorized into three distinct groups: (1) individuals presenting rheumatological symptoms associated with long COVID, (2) patients who have successfully recovered from COVID-19, and (3) donors who have never contracted COVID-19. A notable decline in the expression of miR-200c-3p, miR-766-3p, and miR-142-3p was identified among patients exhibiting rheumatological symptoms of long COVID. The highest concentration of miR-142-3p was found in healthy donors. One potential way to reduce miRNA concentrations is through antibody-mediated hydrolysis. Not only can antibodies possessing RNA-hydrolyzing activity recognize the miRNA substrate specifically, but they also catalyze its hydrolysis. The analysis of the catalytic activity of plasma antibodies revealed that antibodies from patients with long COVID demonstrated lower hydrolysis activity against five fluorescently labeled oligonucleotide sequences corresponding to the Flu-miR-146b-5p, Flu-miR-766-3p, Flu-miR-4742-3p, and Flu-miR-142-3p miRNAs and increased activity against the Flu-miR-378a-3p miRNA compared to other patient groups. The changes in miRNA concentrations and antibody-mediated hydrolysis of miRNAs are assumed to have a complex regulatory mechanism that is linked to gene pathways associated with the immune system. We demonstrate that all six miRNAs under analysis are associated with a large number of signaling pathways associated with immune response-associated pathways.

Acute arterial thrombosis is a rare but dangerous condition that requires rapid diagnosis and treatment to reduce the risk of amputation. SARS-CoV-2 is associated with an increased risk of arterial thrombosis. Point-of-care ultrasound (POCUS) can facilitate rapid bedside evaluation for both venous and arterial thrombosis and expedite treatment in these time-sensitive diagnoses. Although POCUS diagnosis of venous thrombosis is well studied, few cases of POCUS diagnosis of arterial thrombosis have been reported. We present a case in which acute SARS-CoV-2-associated arterial and venous thromboses were diagnosed at the bedside utilizing POCUS, which led to expedited operative management and limb preservation.

The COVID-19 pandemic resulted in cessation and subsequent reduction of routine care including the outpatient ultrasound surveillance of AVF. This un-planned service disruption allowed evaluation of effectiveness of US surveillance in reducing AVF/AVG thrombosis.

This study was a secondary data analysis of monthly access patency for all in-centre patients receiving haemodialysis using an AVF or AVG over a 2-year period (April 2019-March 2021). The study included 298 patients with age, access type, patency and COVID status measured as variables. Thrombosis rates for the 12 months prior to COVID-19 and then during the first 12 months of the pandemic were also measured. Statistical analysis to assess mean and standard deviation for relevant variables was used. A p-value of <0.05 was deemed significant.

At the end of the study an increase in thrombosis rate (%) in the non-surveillance year was observed ((1.20) thrombosis/patient/year in the surveillance group vs (1.68) thrombosis/patient/year in the non-surveillance group). Monthly mean of thrombosed access during surveillance (M = 3.58, 95% CI 2.19-4.98, SD = 2.193) and non-surveillance (M = 4.92, 95% CI 3.52-6.31, SD = 2.19); t(7148) = 2.051, p = 0.038.

Reduction in routine Ultrasound surveillance following the COVID-19 pandemic was associated with a significant increase in access thrombosis rate. Further research is needed to unpick whether the associations seen were directly due to service changes, associated with COVID-19 or other factors during the pandemic. This association was independent of SARS-CoV-2 infection status. Clinical teams should consider alternative service delivery options including out-reach, bedside surveillance to balance risks of access thrombosis versus reducing the risk of nosocomial infection with hospital visits.

Severe deficiency of ADAMTS13 (<10 iu/dL) is diagnostic of thrombotic thrombocytopenic purpura (TTP) and leads to accumulation of ultra-large vWF multimers, platelet aggregation, and widespread microthrombi, which can be life-threatening. However, the clinical implications of a low ADAMTS13 activity level are not only important in an acute episode of TTP. In this article, we discuss the effects of low ADAMTS13 activity in congenital and immune-mediated TTP patients not only at presentation but once in a clinical remission. Evidence is emerging of the clinical effects of low ADAMTS13 activity in other disease areas outside of TTP, and here, we explore the wider impact of low ADAMTS13 activity on the vascular endothelium and the potential for recombinant ADAMTS13 therapy in other thrombotic disease states.

Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH.

This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality.

Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test).

The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

The first dose of COVID-19 vaccines led to an overall reduction in cardiovascular events, and in rare cases, cardiovascular complications. There is less information about the effect of second and booster doses on cardiovascular diseases. Using longitudinal health records from 45.7 million adults in England between December 2020 and January 2022, our study compared the incidence of thrombotic and cardiovascular complications up to 26 weeks after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA-1273). These findings support the wide uptake of future COVID-19 vaccination programs.

To assess the frequency of clinical cardiovascular outcomes for people hospitalised with coronavirus disease 2019 (COVID-19), and the impact of vaccination.

Observational cohort study.

All index admissions of adults with laboratory-confirmed COVID-19 to 21 hospitals participating in the Australian Cardiovascular COVID-19 Registry (AUS-COVID), 4 September 2020 - 11 July 2022.

Frequency of elevated troponin levels, new arrhythmia, new or deteriorating heart failure or cardiomyopathy, new pericarditis or myocarditis, new permanent pacemaker or implantable cardioverter-defibrillator, and pulmonary embolism.

impact of COVID-19 vaccination on likelihood of in-hospital death, intubation, troponin elevation, and clinical cardiovascular events.

The mean age of the 1714 people admitted to hospital with COVID-19 was 60.1 years (standard deviation, 20.6 years); 926 were men (54.0%), 181 patients died during their index admissions (10.6%), 299 required intensive care (17.4%). Thirty-eight patients (2.6%) developed new atrial fibrillation or flutter, 27 (2.6%) had pulmonary embolisms, new heart failure or cardiomyopathy was identified in 13 (0.9%), and pre-existing cardiomyopathy or heart failure was exacerbated in 21 of 110 patients (19%). Troponin was elevated in 369 of the 986 patients for whom it was assessed (37.4%); in-hospital mortality was higher for people with elevated troponin levels (86, 23% v 23, 3.7%; P < 0.001). The COVID-19 vaccination status of 580 patients was known (no doses, 232; at least one dose, 348). The likelihood of in-hospital death (adjusted odds ratio [aOR], 0.38; 95% confidence interval [CI], 0.18-0.79) and intubation (aOR, 0.30; 95% CI, 0.15-0.61) were lower for people who had received at least one vaccine dose, but not the likelihood of troponin elevation (aOR, 1.44; 95% CI, 0.80-2.58) or clinical cardiovascular events (aOR, 1.56; 95% CI, 0.59-4.16).

Although troponin levels were elevated in a considerable proportion of people hospitalised with COVID-19, clinical cardiovascular events were infrequent, and their likelihood was not influenced by vaccination. COVID-19 vaccination, however, was associated with reduced likelihood of in-hospital death and intubation.

Australian and New Zealand Clinical Trials Registry, ACTRN12620000486921 (prospective).

Classical pulmonary thromboembolism (TE) and local pulmonary thrombosis (PT) have been suggested as mechanisms of thrombosis in COVID-19. However, robust evidence is still lacking because this was mainly based on retrospective studies, in which patients were included when TE was suspected.

All patients with COVID-19 pneumonia underwent computed tomography and pulmonary angiography in a prospective study. The main objective was to determine the number and percentage of thrombi surrounded by lung opacification (TSO) in each patient, as well as their relationship with percentage of lung involvement (TLI), to distinguish classical TE (with a random location of thrombi that should correspond to a percentage of TSO equivalent to the TLI) from PT. We determined TLI by artificial intelligence. Analyses at patient level (TLI and percentage of TSO) and at thrombi level (TLI and TSO) were performed.

We diagnosed TE in 70 out of 184 patients. Three (2-8) thrombi/patient were detected. The percentage of TSO was 100% (75-100) per patient, and TLI was 19.9% (4.6-35.2). Sixty-five patients (92.9%) were above the random scenario with higher percentage of TSO than TLI. Most thrombi were TSO (n = 299, 75.1%). When evaluating by TLI (<10%, 10%-20%, 20%-30% and >30%), percentage of TSO was higher in most groups. Thrombi were mainly in subsegmental/segmental arteries, and percentage of TSO was higher in all locations.

Thrombi in COVID-19 were found within lung opacities in a higher percentage than lung involvement, regardless of TLI and clot location, supporting the hypothesis of local PT rather than "classic TE".