COVID-19-associated acute respiratory distress syndrome (ARDS) has challenged healthcare systems, initially resembling classical ARDS but later recognized as distinct. Unique features such as endothelial injury, microthrombosis, and dysregulated inflammation influenced treatment efficacy. Understanding its evolution is key to optimizing therapy and improving outcomes.

This review synthesizes current evidence on COVID-19-associated ARDS, covering epidemiology, pathophysiology, clinical phenotypes, and treatments. It explores the shift from L and H phenotypes to a refined disease model and highlights key therapies, including corticosteroids, immunomodulators, prone positioning, ECMO, and vaccination's impact on severity and ARDS incidence.

At the onset of the COVID-19 pandemic in December 2019, uncertainty was overwhelming. Early clinical guidelines relied on case reports and small case series, offering only preliminary insights into disease progression and management. Despite the initial chaos, the scientific community launched an unprecedented research effort, with over 11,000 clinical trials registered on ClinicalTrials.gov investigating COVID-19 treatments. Several evidence-based strategies emerged as gold standards for managing COVID-19-associated acute respiratory distress syndrome, surpassing prior approaches. The pandemic exposed vulnerabilities in global healthcare, reshaped modern medicine, accelerated innovation, and reinforced the essential role of evidence-based practice in critical care and public health policy.

COVID-19 is associated with intense systemic inflammation and abnormal coagulation profile, leading to an increased incidence of pulmonary embolism (PE).

This study investigates whether PE in COVID-19 patients has different clinical, laboratory, and radiological characteristics compared with traditional PE in COVID-19-negative patients.

We conducted an observational, multicentric, cross-sectional study on consecutive patients diagnosed with PE at admission or during hospital stay from February 21, 2019, to February 20, 2021. We compared clinical and laboratory data and computed tomography images between COVID-19-positive and COVID-19-negative patients. The extent of PE was evaluated using the Qanadli Index.

Among 771 enrolled patients with acute PE, 89 were COVID-19-positive. COVID-19 patients were predominantly male (59.6% vs 41.5%, P = .001) and exhibited fewer classic venous thromboembolism (VTE) risk factors, such as previous VTE (3.5% vs 11.5%, P = .02) and active cancer (4.7% vs 24.2%, P < .0001). Additionally, these patients showed lower median troponin T and pro-B-type-natriuretic-peptide levels (10 vs 32 ng/L, P = .0002; and 383 vs 1448 pg/mL, P = .004, respectively), a lower median Qanadli Index (4 vs 7, P = .0013), more distal PE obstructions (53.5% vs 32.9%, P < .001), and less frequent right ventricular dilatation (4.1% vs 10.9%, P = .09).

In COVID-19 patients, traditional VTE risk factors were less frequent, a possible role for in situ thrombo-inflammatory processes. The reduced radiological extent and severity of PE observed in COVID-19 patients may reflect an in situ thrombo-inflammatory process rather than classical embolization; however, this hypothesis needs to be confirmed by other studies.

The aim of this study was to evaluate the association between SARS-CoV-2 vaccination and the occurrence of thrombotic complications in patients admitted to intensive care for severe COVID-19 pneumonia.

Observational, descriptive, prospective, multicentre study.

Intensive care units of five university hospitals.

A total of 255 patients admitted to the intensive care unit (ICU) with SARS-CoV-2 pneumonia, confirmed by RT-PCR in throat swab or tracheal aspirate, starting the date the first vaccinated patient against SARS-CoV-2 was admitted in one of the participating ICUs, were included in the analysis.

Vaccination status against SARS-CoV-2 and thrombotic events.

18.8% of patients had received some form of vaccination. Thrombotic events occurred in 21.2% of patients. Lack of vaccination was associated with thrombotic events (OR 5.024; 95% CI: 1.104-23.123; p = 0.0037) and death (OR 5.161; 95% CI: 1.075-24.787; p = 0.04). ICU mortality was not associated with the occurrence of thrombotic complications.

In this series of patients, vaccination against SARS-CoV-2 reduced the risk of thrombotic events and mortality in patients with severe COVID-19 admitted to the ICU. Thrombotic complications did not alter ICU mortality.

Research on extracorporeal membrane oxygenation (ECMO)-assisted support for pulmonary embolism (PE) has been increasing, yet no systematic bibliometric analysis has been conducted. This study evaluates global research trends in this field by analyzing countries, institutions, authors, journals, references, and keywords.

Relevant articles and reviews published up to August 15, 2023, were retrieved from the Web of Science Core Collection (WOSCC). VOSviewer and CiteSpace software were used for bibliometric analysis of collected data.

Publications on ECMO-assisted support for PE surged from 2015 to 2023, comprising 82.7% (306/370) of total studies. The United States, Germany, and China contributed 62.97% (233/370) of the research. Perfusion-UK had the most publications, while Journal of the American College of Cardiology was the most cited journal. The University of Maryland, Massachusetts General Hospital, and Harvard Medical School were the leading institutions. Chetan Pasrija published the highest number of papers, while Konstantinidis SV was the most co-cited author. Research hot spots include: (1) ECMO management and survival rates, (2) combined treatments with thrombolysis or surgical thrombectomy, (3) anticoagulation and clot formation, and (4) ECMO support in COVID-19.

This study aims to increase awareness of research hot spots on ECMO-assisted support for PE by determining the collaboration and impact of authors, countries, institutions, and journals. In addition, it comprehensively reviews research trends on ECMO regarding PE. It also provides a reference for potential collaborators, institutions, and future research prospects.

This study aimed to assess the impact of SARS-CoV-2 therapies on the risk of venous thromboembolism (VTE) and other cardiovascular events. A retrospective, multicenter, observational study included hospitalized patients in Spain due to acute SARS-CoV-2 infection from March 2020 to March 2022. A total of 184,324 hospitalized COVID-19 patients were included, with a mean age of 67.5 (± 16) years of whom 58.4% were male. Among the comorbidities, arterial hypertension was the most common, affecting 52.5% (9618 patients), followed by dyslipidemia in 39.5% (7237 patients), diabetes mellitus in 23.7% (1748 patients), and atrial fibrillation in 10.6% (1948 patients). The overall mortality rate was 17.4% (3183 patients) and 9.9% (1819 patients) required admission to an intensive care unit. Cardiovascular events occurred in 4.08% (748 patients), with VTE occurring in 2.78% (510 patients), myocardial infarction in 0.75% (137 patients), and ischemic stroke in 0.55% (101 patients). Among therapies, beta-lactams were used in 66.7% (12,228 patients), systemic corticosteroids in 56.9% (10,424 patients), and tocilizumab in 11.6% (2128 patients). Multivariate analysis revealed an independent association between VTE and the use of tocilizumab (adjusted OR 2.07; p < 0.01), corticosteroids (adjusted OR 1.44; p = 0.02), and macrolides (adjusted OR 0.58; p < 0.01). None of the therapies were associated with the risk of myocardial infarction or ischemic stroke. In this large national cohort, tocilizumab and corticosteroids exhibited an independent association for the risk of VTE, but not for myocardial infarction or ischemic stroke.

Thromboembolic (TE) complications in COVID-19 patients are rising globally, contributing significantly to mortality, particularly in severe cases. However, their prevalence, characteristics, and impact on mortality in Malaysia remain unclear.

This study aimed to determine the prevalence of thromboembolic (TE) events and associated mortality among COVID-19 patients admitted within a single centre intensive care unit (ICU). The proportions of patients with TE events who died, and factors associated with TE events were explored.

In this retrospective cohort study, patients with PCR confirmed SARS-CoV-2 virus and who received thromboprophylaxis within February 2020-2021 were included. TE event is a combination of venous [(deep vein thrombosis (DVT), pulmonary embolism (PE)] and arterial (myocardial infarction (MI), stroke) thromboembolism.

Mean (SD) age 56.6 (13.7), 63.5% were male, 61.6% Malays, median (IQR) 7 (3-14) days of ICU stay, 64.2%, 53.2% and 20.9% had underlying hypertension, diabetes and obesity respectively. In total, 240 (44.9%) developed TE event. Significantly higher proportions of COVID-19 patients who developed complications of DVT (2.5% vs. 0.2%; p = 0.013), PE (47.5% vs 34.0%; p = 0.006), stroke (12.3% vs. 1.5; p<0.001) and MI (16.4% vs. 4.6%; p<0.001) died. Predictors of TE events were age [HR 1.01 (95% CI 1.00-1.02)], obesity [HR 1.98 (95% CI 1.51-2.6)], D-dimer [HR 1.01 (95% CI 1.00-1.01)], and duration of ICU stay [HR 0.98 (95% CI 0.97-0.99)].

In severely ill COVID-19 patients, TE complications were common, and patients with DVT, PE, stroke, or MI faced increased mortality, even with thromboprophylaxis. Age, obesity, elevated D-Dimer levels, and longer ICU stays were significant predictors of TE events. Considering these findings, a more aggressive approach, combining thromboprophylaxis with enhanced anti-inflammatory treatments, may be necessary for high-risk COVID-19 ICU patients to reduce TE events and mortality.

Arterial stiffness was reported with corona virus disease 2019 (COVID-19). We studied atherosclerosis in COVID-19 directly through duplex ultrasound measurements and their relation to co-morbidities, clinical and laboratory severity markers, and serum interleukin (IL) 6 and 17. Serum IL 6 and 17, average carotid intima-media thickness (cIMT), diameter and peak systolic velocities (PSV) of tibial, ulnar, radial arteries, and ankle brachial index (ABI) were measured in 44 COVID-19 patients and 44 healthy controls. Serum IL6, IL17, PSV, and cIMT were higher while diameter was lower (P ≤ .01) in cases. Clinical severity index correlated positively with age, co-morbidities, ferritin, IL6, IL17, cIMT, and PSV (P ≤ .04) and negatively with diameter and ABI (P = .04). Patients with severe lymphopenia had higher PSV, IL6, and IL17 and lower diameter (P < .00001). Ferritin positively correlated with PSV and negatively with diameter and ABI (P ≤ .01). Those who received an IL6 inhibitor (tocilizumab) showed lower PSV and higher diameter (P ≤ .01). In multiple regression analysis, IL17 and (age, co-morbidities) were related to (PSV, diameter) and cIMT (P ≤ .001, ≤0.02), respectively. COVID-19 may be associated with subclinical acute and may be reversible atherosclerosis severely involving peripheral arteries.

We aimed to investigate the incidence of new acute myocardial infarction (AMI), in patients with Coronavirus disease (COVID-19) who had old MI. We hypothesized that COVID-19 increases the rate of repeated AMI in this population regardless of age and gender.

A retrospective analysis was conducted for adult patients admitted with COVID-19 and developed thromboembolic event (TEE) in 2020. Patients were categorized based on the history of old MI, new MI, age, and gender.

Among 16,903 patients with COVID-19 who were admitted, 210 (1.2%) developed TEE (89% were males, 55% were <55 years old, and 80.5% had an old MI). COVID-19 was severe in 32% of cases. AMI occurred in 160 patients (42.5% STEMI and 57.5% NSTEMI). In patients with prior MI, 92.5% developed another AMI. NSTEMI was higher in patients with severe COVID-19 than STEMI (33% vs 21%). Patients with severe COVID-19 had higher mortality (39.4% vs 5.6%), fewer rates of prior MI (74% vs 83%), hypertension (40% vs 60%), and STEMI (31.8% vs 46.5%) than mild COVID-19 patients. On multivariable analysis, COVID-19 severity was an independent predictor of mortality (OR10; 95%CI 1.62-67.19) after adjustment for age, gender, diabetes mellitus, C-reactive protein, serum Ferritin, Procalcitonin, and Fibrinogen values, and prior or new MI.

Patients with old MI could develop a new AMI in 80% of COVID-19. However, the mortality was higher in patients without a history of MI due to the severity of COVID-19. Attention should be given to patients who possess thrombotic risk factors in pandemics.

Introduction. Post-coronavirus disease-2019 (COVID-19) patients may develop cardiac symptoms. We hypothesized that cardiovascular magnetic resonance (CMR) can assess the background of post-COVID-19 cardiac symptoms using multi-parametric evaluation. We aimed to conduct an investigation of symptomatic patients with post-COVID-19 syndrome using CMR (INSPIRE-CMR). Methods. INSIPRE-CMR is a retrospective multicenter study including 174 patients from five centers referred for CMR due to cardiac symptoms. CMR was performed using 3.0 T/1.5 T system (24%/76%, respectively). Myocardial inflammation was determined by the updated Lake Louise criteria. Results. Further, 174 patients with median age of 40 years (IQR: 26-54), 72 (41%) were women, and 17 (9.7%) had a history of autoimmune disease, muscular dystrophy, or cancer. In total, 149 (86%) patients were late gadolinium enhanced (LGE)-positive with a non-ischemic pattern, and of those evaluated with the updated Lake Louise criteria, 141/145 (97%) had ≥1 pathologic T1 index. Based on the T2-criterion, 62/173 (36%) patients had ≥1 pathologic T2 index. Collectively, 48/145 (33%) patients had both positive T1- and T2-criterion. A positive T2-criterion or a combination of a positive T1- and T2-criterion were significantly more common amongst patients with severe COVID-19 [45 (31%) vs. 17 (65%), p = 0.001 and 32 (27%) vs. 16 (64%), p < 0.001, respectively]. During the one-year evaluation, available for 65/174 patients, shortness of breath, chest pain, and arrhythmia were identified in 7 (4%), 15 (8.6%), and 43 (24.7%), respectively. CMR evaluation, available in a minority of them, showed mildly reduced LVEF, while nat T1 mapping and EVC remained at levels higher than the normal values of the local MRI units. Conclusions. The majority of post-COVID-19 patients with cardiac symptoms presented non-ischemic LGE and abnormalities in T1 and T2-based indices. Multi-parametric CMR reveals important information on post-COVID-19 patients, supporting its role in short/long-term evaluation.

Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. This study aimed to enhance our understanding of clinical thrombosis in COVID-19, its associated factors, and mortality outcomes.

Hospitalised adult (≥18 years of age) patients with COVID-19 in 2020 were retrospectively identified from the US National Inpatient Sample database. Clinical characteristics, incident VTE, ATE, and in-hospital mortality outcomes were recorded. Multivariable logistic regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients.

A total of 1,583,135 adult patients with COVID-19 in the year 2020 were identified from the National Inpatient Sample database; patients with thrombosis were 41% females with a mean age of 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1% (97,185), including VTE at 4.8% (76,125), ATE at 3.0% (47,790), and the in-hospital mortality rate was 13.4% (212,785). Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p<0.001) compared with patients without thrombosis. The main factors associated with overall thrombosis, VTE, and ATE were paralysis, ventilation, solid tumours without metastasis, metastatic cancer, and acute liver failure. Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p<0.001), they were not in multivariable analyses-thrombosis (odds ratio [OR] 1.24; 95% confidence interval [CI] 0.90-1.70; p=0.19), VTE (OR 0.70; 95% CI 0.52-1.00; p=0.05), and ATE (OR 1.07; 95% CI 0.92-1.25; p=0.36).

The association of COVID-19 with thrombosis and VTE increases with increasing severity of the COVID-19 disease. Risk stratification of thrombosis is crucial in COVID-19 patients to determine the necessity of thromboprophylaxis.

Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed "immunothrombosis". In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms.

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.

One of the hallmarks of coronavirus disease 2019 (COVID-19), particularly in complicated cases (i.e., requiring hospitalization or intensive care support), is persistent hemostasis activation, which may be associated with a vast array of thrombotic episodes involving both the arterial and venous systems. The renewed emphasis on the relationship between viral infections and venous thrombosis paves the way for determining whether a more common and often underestimated infection disease, such as influenza, may also be associated with a significant burden of venous thrombotic episodes, and how this eventual thrombotic risk compares to that seen in COVID-19, both in the past and with newer variants. Our review of studies comparing the burden of venous thromboembolism (VTE) in patients with COVID-19 or influenza revealed that the thrombotic risk appears to be significantly higher in patients with COVID-19 but remains certainly not meaningless in those with influenza, particularly in subjects infected by highly virulent strains (i.e., H1N1), in those who develop pneumonia and require intensive care support. In these specific clinical settings, the adoption of tailored thromboprophylaxis may be indicated though more studies are compellingly needed on this matter. As COVID-19 variants emerge, there is a possibility that the VTE burden of COVID-19 will decrease, and progress to that of other respiratory viruses.

While our understanding of coronavirus disease 2019 (COVID-19) has evolved, uncertainty remains regarding utility of previously established pulmonary embolism (PE) screening guidelines in patients with COVID-19. Many studies have investigated the efficacy of D-dimer (DD) screenings for patients with COVID-19 admitted to inpatient services, but few have evaluated patients in the emergency department (ED). The purpose of this study was to investigate utility of DD threshold for PE screening in patients with COVID-19 presenting to the ED.

This was a retrospective, multicenter cohort including patients presenting to three EDs between March 1, 2020 and February 1, 2021 who tested positive for COVID-19 during ED visit or in 60 days prior to presentation and had DD ordered in ED. Patients were grouped by those who underwent computed tomography pulmonary angiogram (CTPA) to evaluate for PE and those who did not, and descriptive statistics were performed. Those who underwent CTPA were further divided into PE-positive and PE-negative groups. The discriminative ability of DD in predicting PE in patients with COVID-19 was analyzed using the receiver operating characteristic (ROC) curve.

A total of 570 patients with COVID-19 were included in the study, of which 107 underwent CTPA to evaluate for PE. History of diabetes, elevated glucose, elevated lactate dehydrogenase, elevated white blood cell count, elevated platelets, elevated respiratory rate, and lower temperature were associated with increased risk for PE. Compared to those without PE, patients with PE were significantly more likely to be hospitalized (100% vs. 82%, p = 0.020) and admitted to the ICU (64% vs. 24%, p = 0.002). Those with PE had a significantly higher median DD value (21,177 ng/mL) compared to PE-negative group (952 ng/mL, p < 0.001). The ROC curve for DD in predicting PE had an area under the curve of 0.91 (95% confidence interval [0.84, 0.98]). In our study population, the optimal DD threshold for predicting PE was 1815 ng/mL (sensitivity 93% and specificity 80%). A conservative threshold of 1089 ng/mL could be used with sensitivity 100% and specificity 58%.

DD is often elevated in patients with COVID-19, regardless of PE. While the classically used DD cutoff is 500 ng/mL, our study demonstrated a threshold of 1089 ng/mL safely predicted PE in patients with COVID-19 .

Coronavirus disease of 2019 (COVID-19) is the respiratory viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite being a primary respiratory illness, it is commonly complicated by systemic involvement of the vasculature leading to arterial and venous thrombosis. In this review, we will focus on the association between COVID-19 and thrombosis. We will highlight the pathophysiology of COVID-19 coagulopathy. The clinical manifestations of COVID-19 vasculopathy will be discussed with a focus on venous and arterial thromboembolic events. COVID-19 vasculopathy and disseminated intravascular coagulation (DIC) are distinguished within, as well as areas of controversy, such as "long COVID". Finally, the current professional guidelines on prevention and treatment of thrombosis associated with SARS-CoV-2 infection will be discussed.

COVID-19 disease is associated with a hyperinflammatory, pro-thrombotic state and a high mortality. Our primary objective was to assess the change in inflammatory and thrombotic markers associated with PEX, and secondary objectives were to assess the effects of PEX on progression of respiratory failure and incidence of acute thrombotic events. We conducted a prospective, phase II, non-blinded randomised control trial of plasma exchange compared to standard of care in critically ill adults with severe COVID-19 associated respiratory failure, requiring supplemental oxygen or ventilatory support and elevated thrombo-inflammatory markers (LDH, CRP, ferritin, and D-Dimer). Patients randomised to receive PEX were treated with a daily single volume plasma exchange for a minimum of five days. Twenty-two patients were randomised of who 11 received PEX. Demographic and clinical characteristics were similar between groups at presentation. PEX was associated with a significant reduction in pro-thrombotic markers FVIII, VWF and VWF Ag: ADAMTS 13 ratio (p < 0.001). There were no differences in the reduction of inflammatory markers, severity of respiratory failure (p = 0.7), thrombotic events (p = 0.67), or mortality (p > 0.99) at 28 days. PEX successfully reduced pro-thrombotic markers, although was not associated with reduction in inflammatory markers, respiratory failure, or thrombotic events.Trial registration: (NCT04623255); first posted on 10/11/2020.

Sinus thrombosis is a common post-operative finding after posterior fossa surgery performed in the vicinity of the dural venous sinuses. The SARS-CoV-2 virus has been shown to confer an increased risk of venous thromboembolic events owing to eliciting a hyper-inflammatory and pro-thrombotic state. In this study, we examine the incidence of post-operative venous sinus thrombosis in patients undergoing peri-sigmoid posterior fossa surgery in the pre- and post-COVID era and investigate whether COVID infection confers an increased risk of sinus thrombosis.

A retrospective review of a single institution case series of patients underwent peri-sigmoid surgery (retrosigmoid, translabyrinthine, or far lateral) approach. Relevant clinical variables were investigated that may confer an increased risk of sinus thrombosis.

A total of 311 patients (178 in the pre-COVID era, and 133 operated on after the pandemic began in March 2020) are included in the study. The composite incidence of sinus thrombosis seen on post-operative imaging was 7.8%. The incidence of sinus thrombosis in the pre-COVID cohort was N = 12 patients (6.7%) versus N = 12 (9%) in the post-COVID cohort (p = 0.46). A history of COVID infection was not shown to confer an increased risk of post-operative sinus thrombosis (OR: 0.61; 95% CI: 0.08-4.79, p = 0.64). Only a small number of patients (N = 7, 2.3%) required either medical or surgical intervention for post-operative sinus thrombosis.

The overall incidence of post-operative sinus thrombosis is similar in the pre- and post-COVID era. The findings of this study suggest that COVID infection is not associated with a higher risk of venous sinus thrombosis.

Objective: Observational studies show the correlation between COVID-19 and venous thromboembolism (VTE) risk. However, the causal effects remain uncertain. We aimed to explore the potential causal association between COVID-19 and VTE using Mendelian randomization (MR) design. Methods: Two-sample MR was used to evaluate the potential causality between COVID-19 and VTE by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The weighted median, MR-Egger, simple mode, and weighted mode were employed as supplementary methods for MR estimations, with the inverse-variance weighted (IVW) method serving as the principal analysis. In addition, we took sensitivity analyses, including Cochran's test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analysis to ensure that we obtained stable and reliable results. Results: Our study selected 26 COVID-19 severity, 31 COVID-19 hospitalization, and 13 COVID-19 susceptibility SNPs as instrumental variables. The IVW analysis results revealed that there was no causal relationship between COVID-19 severity, hospitalization, or susceptibility and VTE, with odds ratios of 0.974 (95%CI: 0.936-1.013, p = 0.19), 0.976 (95%CI: 0.918-1.039, p = 0.447), and 0.908 (95%CI: 0.775-1.065, p = 0.235), respectively. The IVW approach yielded consistent results with MR-Egger, Weighted Median simple mode, and weighted mode. MR-PRESSO and sensitivity analysis further confirmed the stability and consistency of the MR results. Conclusions: This study did not find evidence to support a causal relationship between COVID-19 and VTE at the genetic level. Further investigation is warranted to determine if the significant association reported in previous observational studies between the two is due to confounding factors.

The coronavirus disease 2019 (COVID-19) pandemic has unveiled numerous clinical challenges, particularly its association with thrombotic events, which significantly contribute to morbidity and mortality. While thrombotic complications such as arterial and venous thromboembolism (VTE) are well-documented, instances of intracardiac thrombus are notably rare. This case report discusses a 60-year-old male with COVID-19 who came to the hospital due to respiratory distress. Despite treatment with remdesivir, the patient's condition worsened prompting further workup. His nuclear medicine (NM) ventilation-perfusion scan was inconclusive, but a 2D echocardiogram showed an intracardiac thrombus in the right atrium (RA) and right ventricle (RV). As the patient's condition worsened, necessitating a transition from nasal cannula to high-flow nasal cannula, a decision was made to treat him with intravenous (IV) thrombolytic therapy. The patient received 100 mg IV alteplase and IV heparin, resulting in significant respiratory improvement and symptomatic relief. A repeat echocardiogram after 48 hours showed normal ejection fraction and complete thrombus resolution. In conclusion, this case highlights the complex link between COVID-19 infection and prothrombotic states, leading to severe complications such as intracardiac thrombus in transit. The successful treatment of this patient through a multidisciplinary approach and thrombolytic therapy underscores the importance of prompt recognition and intervention in high-risk cases.

COVID-19 associates with a hypercoagulant state and an increased risk for venous thromboembolic events (VTEs). Whether severe COVID-19 infection requiring extracorporeal membrane oxygenation (ECMO) support might lead to chronic pulmonary perfusion abnormalities and chronic thromboembolic pulmonary disease/hypertension remains unclear. The purpose of this study was to evaluate chronic pulmonary perfusion abnormalities in long-term survivors of COVID-19-related severe acute respiratory distress syndrome (ARDS) treated by ECMO at our institution. Pulmonary perfusion was examined by ventilation/perfusion (V/Q) single-photon emission computed tomography or V/Q planar scintigraphy at least 3 months after ECMO explantation, comorbidities and incidence of thromboembolic events were recorded as well. Of 172 COVID-19 patients treated by ECMO for severe COVID-19 pneumonia between March 2020 and November 2021, only 80 were successfully weaned from ECMO. Of those, 37 patients were enrolled into the present analysis (27% female, mean age 52 years). Median duration of ECMO support was 12 days. In 24 (65%) patients VTE was recorded in the acute phase (23 patients developed ECMO cannula-related deep vein thrombosis, 5 of them had also a pulmonary embolism, and one thrombus was associated with a central catheter). The median duration between ECMO explantation and assessment of pulmonary perfusion was 420 days. No segmental or larger mismatched perfusion defects were then detected in any patient. In conclusion, in long-term survivors of COVID-19-related ARDS treated by ECMO, no persistent pulmonary perfusion abnormalities were detected although VTE was common.

The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE.

A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued.

Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences.

In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings.

Sanofi and Rovi, Sanofi Spain.

Ratio of arterial pressure of oxygen and fraction of inspired oxygen (P/F ratio) together with the fractional dead space (Vd/Vt) provides a global assessment of pulmonary gas exchange. The aim of this study was to assess the potential value of these variables to prognosticate 90-day survival in patients with COVID-19 associated ARDS admitted to the Intensive Care Unit (ICU) for invasive ventilatory support.

In this single-center observational, retrospective study, P/F ratios and Vd/Vt were assessed up to 4 weeks after ICU-admission. Measurements from the first 2 weeks were used to evaluate the predictive value of P/F ratio and Vd/Vt for 90-day mortality and reported by the adjusted hazard ratio (HR) and 95% confidence intervals [95%CI] by Cox proportional hazard regression.

Almost 20,000 blood gases in 130 patients were analyzed. The overall 90-day mortality was 30% and using the data from the first ICU week, the HR was 0.85 [0.77-0.94] for every 10 mmHg increase in P/F ratio and 1.61 [1.20-2.16] for every 0.1 increase in Vd/Vt. In the second week, the HR for 90-day mortality was 0.82 [0.75-0.89] for every 10 mmHg increase in P/F ratio and 1.97 [1.42-2.73] for every 0.1 increase in Vd/Vt.

The progressive changes in P/F ratio and Vd/Vt in the first 2 weeks of invasive ventilatory support for COVID-19 ARDS were significant predictors for 90-day mortality.

Microthrombus is one of the major causes of the sequelae of Corona Virus Disease 2019 (COVID-19 and leads to subsequent embolism and necrosis. Due to their small size and irregular movements, the early detection and efficient removal of microthrombi in vivo remain a great challenge. In this work, an interventional method is developed to identify and remove the traveling microthrombi using targeted-magnetic-microbubbles (TMMBs) and an interventional magnetic catheter. The thrombus-targeted drugs are coated on the TMMBs and magnetic nanoparticles are shelled inside, which allow not only targeted adhesion onto the traveling microthrombi, but also the effective capture by the magnetic catheter in the vessel. In the proof-of-concept experiments in the rat models, the concentration of microthrombus is reduced by more than 60% in 3 min, without damaging the organs. It is a promising method for treating microthrombus issues.

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).

The Coronavirus Disease 2019 (COVID-19), caused by the virus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a global public health problem in which atypical findings other than the usual fever and respiratory symptoms render early diagnosis and treatment difficult. Cases with atypical clinical and laboratory presentations continue to pose a challenge in the treatment and control of the disease. This case report aims to share our follow-up and treatment experience in a patient considered to have antithrombin III (ATIII) deficiency based on activated clotting time (ACT) levels unresponsive to heparin who was admitted to intensive care unit due to COVID-19-induced cytokine storm associated with extreme D-dimer elevation (>65,000 μg/L).

Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.

Venous thromboembolism (VTE) is known to be intricately linked to severe COVID-19 (sCOVID-19) occurrence. Herein, we employed univariable Mendelian randomization (MR) and transcriptome analysis to predict the causal association and associated signaling networks between VTE and sCOVID-19.

Potential VTE and sCOVID-19 association was assessed using MR-Egger, weighted median, simple mode, weighted mode, and inverse variance weighted (IVW) regression. We conducted independent univariable analyses involving VTE and sCOVID-19. Using heterogeneity, pleiotropy, and the Leave-One-Out examinations, we performed sensitivity analyses. Thereafter, we performed transcriptome analysis of the GSE164805 dataset to identify differentially expressed genes (DEGs) linked to single nucleotide polymorphisms (SNPs). Lastly, we conducted immune analyses.

Based on our univariable analysis, VTE was a strong indicator of sCOVID-19 development, and it was intricately linked to sCOVID-19. We further conducted sensitivity analysis to demonstrate the reliability of our results. Using differential analysis, we identified 15 major genes, namely, ACSS2, CEP250, CYP4V2, DDB2, EIF6, GBGT1, GSS, MADD, MAPK8IP1, MMP24, YBPC3, NT5DC3, PROCR, SURF6, and YIPF2, which were strongly connected to suppressive adaptive immune as well as augmented inflammatory cells. In addition, we uncovered strong associations with most differential immunologic gene sets, such as, the Major Histocompatibility Complex (MHC), immunoactivators, and immunosuppressors.

Herein, we demonstrated we strong association between VTE and enhanced sCOVID-19 risk. We also identified 15 DEGs which potentially contribute to the shared immunologic pathogenesis between VTE and sCOVID-19.

In out-of-hours primary care (OHS-PC), semi-automatic decision support tools are often used during telephone triage. In the Netherlands, the Netherlands Triage Standard (NTS) is used. The NTS is mainly expert-based and evidence on the diagnostic accuracy of the NTS' urgency allocation against clinically relevant outcomes for patients calling with shortness of breath (SOB) is lacking.

We included data from adults (≥18 years) who contacted two large Dutch OHS-PC centres for SOB between 1 September 2020 and 31 August 2021 and whose follow-up data about final diagnosis could be retrieved from their own general practitioner (GP). The diagnostic accuracy (sensitivity and specificity with corresponding 95% confidence intervals (CI)) of the NTS' urgency levels (high (U1/U2) versus low (U3/U4/U5) and 'final' urgency levels (including overruling of the urgency by triage nurses or supervising general practitioners (GPs)) was determined with life-threatening events (LTEs) as the reference. LTEs included, amongst others, acute coronary syndrome, pulmonary embolism, acute heart failure and severe pneumonia.

Out of 2012 eligible triage calls, we could include 1833 adults with SOB who called the OHS-PC, mean age 53.3 (SD 21.5) years, 55.5% female, and 16.6% showed to have had a LTE. Most often severe COVID-19 infection (6.0%), acute heart failure (2.6%), severe COPD exacerbation (2.1%) or severe pneumonia (1.9%). The NTS urgency level had a sensitivity of 0.56 (95% CI 0.50-0.61) and specificity of 0.61 (95% CI 0.58-0.63). Overruling of the NTS' urgency allocation by triage nurses and/or supervising GPs did not impact sensitivity (0.56 vs. 0.54, p = 0.458) but slightly improved specificity (0.61 vs. 0.65, p < 0.001).

The semi-automatic decision support tool NTS performs poorly with respect to safety (sensitivity) and efficiency (specificity) of urgency allocation in adults calling Dutch OHS-PC with SOB. There is room for improvement of telephone triage in patients calling OHS-PC with SOB.

The Netherlands Trial Register, number: NL9682 .

Patients with coronavirus disease 2019 (COVID-19) were vulnerable to venous thromboembolism (VTE), which further increases the risk of unfavorable outcomes. However, neither genetic correlations nor shared genes underlying COVID-19 and VTE are well understood.

This study aimed to characterize genetic correlations and common pathogenic mechanisms between COVID-19 and VTE.

We used linkage disequilibrium score (LDSC) regression and Mendelian Randomization (MR) analysis to investigate the genetic associations and causal effects between COVID-19 and VTE, respectively. Then, the COVID-19 and VTE-related datasets were obtained from the Gene Expression Omnibus (GEO) database and analyzed by bioinformatics and systems biology approaches with R software, including weighted gene co-expression network analysis (WGCNA), enrichment analysis, and single-cell transcriptome sequencing analysis. The miRNA-genes and transcription factor (TF)-genes interaction networks were conducted by NetworkAnalyst. We performed the secondary analysis of the ATAC-seq and Chip-seq datasets to address the epigenetic-regulating relationship of the shared genes.

This study demonstrated positive correlations between VTE and COVID-19 by LDSC and bidirectional MR analysis. A total of 26 potential shared genes were discovered from the COVID-19 dataset (GSE196822) and the VTE dataset (GSE19151), with 19 genes showing positive associations and 7 genes exhibiting negative associations with these diseases. After incorporating two additional datasets, GSE164805 (COVID-19) and GSE48000 (VTE), two hub genes TP53I3 and SLPI were identified and showed up-regulation and diagnostic capabilities in both illnesses. Furthermore, this study illustrated the landscapes of immune processes in COVID-19 and VTE, revealing the downregulation in effector memory CD8+ T cells and activated B cells. The single-cell sequencing analysis suggested that the hub genes were predominantly expressed in the monocytes of COVID-19 patients at high levels. Additionally, we identified common regulators of hub genes, including five miRNAs (miR-1-3p, miR-203a-3p, miR-210-3p, miR-603, and miR-124-3p) and one transcription factor (RELA).

Collectively, our results highlighted the significant correlations between COVID-19 and VTE and pinpointed TP53I3 and SLPI as hub genes that potentially link the severity of both conditions. The hub genes and their common regulators might present an opportunity for the simultaneous treatment of these two diseases.

Introduction Coronavirus-19 (COVID-19) plays a vital role in viral-induced hypercoagulability through the initiation of a cytokine storm. This mechanism has been found to predispose unvaccinated patients to systemic complications including arterial thrombosis (AT) with poor 30-day amputation-free survival rates. There remains, however, little understanding regarding the incidence in patients who have received a COVID-19 vaccination. This study aims to assess the incidence, management and outcomes of vaccinated patients with COVID-19 who develop thrombotic complications to reduce amputation and direct mortality. Methods The case notes of all emergency patients with COVID-19 referred to the vascular services in a tertiary referral centre between November 2021 and April 2022 were reviewed. Patients who were unvaccinated or admitted with stroke or coronary thrombosis were excluded. The study was undertaken to measure 30-day outcomes. Results Between November 2021 and April 2022, 167,290 people tested positive for COVID-19 in Norfolk. Thirty-one patients under the vascular service had COVID-19, of which, one patient was unvaccinated. Only one vaccinated patient was referred with AT and had a positive COVID-19 result two days after admission. Above-knee amputation was performed within 30 days and he survived. Seventeen percent of patients contracted COVID-19 during their hospital admission. Conclusion The incidence of acute limb ischaemia in vaccinated patients is low; however, the 30-day outcomes remain poor. Compared to unvaccinated patients, there was a significant reduction in the presentation of AT in vaccinated patients during that timeframe, despite a higher background number of COVID-19 cases. Therefore, vaccination may minimise the risk of AT.

Lung tissue has a certain regenerative ability and triggers repair procedures after injury. Under controllable conditions, lung tissue can restore normal structure and function. Disruptions in this process can lead to respiratory system failure and even death, causing substantial medical burden. The main types of respiratory diseases are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS). Multiple cells, such as lung epithelial cells, endothelial cells, fibroblasts, and immune cells, are involved in regulating the repair process after lung injury. Although the mechanism that regulates the process of lung repair has not been fully elucidated, clinical trials targeting different cells and signaling pathways have achieved some therapeutic effects in different respiratory diseases. In this review, we provide an overview of the cell type involved in the process of lung regeneration and repair, research models, and summarize molecular mechanisms involved in the regulation of lung regeneration and fibrosis. Moreover, we discuss the current clinical trials of stem cell therapy and pharmacological strategies for COPD, IPF, and ARDS treatment. This review provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, a large number of critically ill and severe COVID-19 patients meet the diagnostic criteria for sepsis and even septic shock. The treatments for COVID-19 patients with sepsis are still very limited. For sepsis, improving ventilation is one of the main treatments. Nitric oxide (NO) and almitrine have been reported to improve oxygenation in patients with "classical" sepsis. Here, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of NO, almitrine, and the combination of both for COVID-19 (at the edge of sepsis) patients. Method: A systematic search was performed on Embase, PubMed, the Cochrane Library, the Web of Science, Wanfang Data, and China National Knowledge Infrastructure. Randomized clinical trials, cohort studies, cross-sectional studies, case-control studies, case series, and case reports in COVID-19 patients with suspected or confirmed sepsis were performed. Study characteristics, patient demographics, interventions, and outcomes were extracted from eligible articles. Results: A total of 35 studies representing 1,701 patients met eligibility criteria. Inhaled NO did not affect the mortality (OR 0.96, 95% CI 0.33-2.8, I2 = 81%, very low certainty), hospital length of stay (SMD 0.62, 95% CI 0.04-1.17, I2 = 83%, very low certainty), and intubation needs (OR 0.82, 95% CI 0.34-1.93, I2 = 56%, very low certainty) of patients with COVID-19 (at the edge of sepsis). Meanwhile, almitrine did not affect the mortality (OR 0.44, 95% CI 0.17-1.13, low certainty), hospital length of stay (SMD 0.00, 95% CI -0.29-0.29, low certainty), intubation needs (OR 0.94, 95% CI 0.5-1.79, low certainty), and SAEs (OR 1.16, 95% CI 0.63-2.15, low certainty). Compared with pre-administration, the PaO2/FiO2 of patients with NO (SMD-0.87, 95% CI -1.08-0.66, I2 = 0%, very low certainty), almitrine (SMD-0.73, 95% CI-1.06-0.4, I2 = 1%, very low certainty), and the combination of both (SMD-0.94, 95% CI-1.71-0.16, I2 = 47%, very low certainty) increased significantly. Conclusion: Inhaled NO, almitrine, and the combination of the two drugs improved oxygenation significantly, but did not affect the patients' mortality, hospitalization duration, and intubation needs. Almitrine did not significantly increase the patients' SAEs. Well-designed high-quality studies are needed for establishing a stronger quality of evidence. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367667, identifier CRD42022367667.