Anticoagulants have an important role in the prevention of cardiovascular disorders. Costus speciosus (Costaceae) is a medicinal herb used to treat COVID-19-induced thrombosis. The purpose of this study was to assess the anticoagulant activity of various C. speciosus aqueous (CSAE), ethanol (SCEE), and methanol (CSME) extracts in vivo and in vitro utilizing thrombin time (TT), activated partial thromboplastin time (aPTT), and prothrombin time (PT). Different concentrations of the three extracts were used to evaluate the anticoagulation effects in vitro. In the in vivo assay, male Sprague Dawley rats were used to test the CSME as in vivo anticoagulants. Three groups of rats included the control group and the groups that received CSME daily at a low (200 mg/kg) or high dose (400 mg/kg b.w) for 2 weeks. The molecular docking of the major bioactive constituents of the methanolic extract against the binding site of the thrombin inhibitor complex was evaluated. The HPLC detected 13, 10 and 11 polyphenols in the methanolic, ethanolic and aqueous extracts, respectively. The in vitro results showed that all the studied extracts had anticoagulant activity and increased aPTT, TT, and PT time. The in vivo experiment supported the in vitro results and demonstrated that CSME greatly prolonged the anticoagulant characteristics when compared to the negative control. Both findings suggested that these extracts have significant anticoagulant activity, with CSME being more effective and potentially useful in pharmaceutical applications as a natural anticoagulant medication.

The aim of the present study was to quantify the rate of thromboembolic events (TE) in pregnant women with SARS-CoV-2 infection and to characterize risk factors to provide a basis for individualized recommendation on prophylactic measures.

CRONOS is a multicenter, prospective observational study conducted in Germany and Austria during the COVID-19 pandemic. Pregnant women with confirmed SARS-CoV-2 infection were enrolled. Data on demographics, medical history, COVID-19-related aspects, and pregnancy and birth outcomes were collected. TE was particularly queried and used as the primary outcome. A combination of "TE," "maternal or fetal death," or "severe postpartum hemorrhage" was defined as a secondary endpoint. Risk analyses were performed using univariate and multivariable logistic regression models.

Data from 8033 pregnant patients showed 40 TEs (0.5% incidence). TE rates were 10% in ICU patients, 0.2-0.4% in those with moderate-to-mild COVID-19, and < 0.1% in asymptomatic women. Pulmonary embolism occurred in 21 cases, deep vein thrombosis in 12, and 7 had atypical or arterial TE. Risk factors included advanced gestational age, COVID-19 symptoms, hospitalization or ICU admission, premature birth, cesarean section, delivery within 4 weeks of infection, higher weight gain, anemia, and chronic inflammatory bowel disease. COVID-19 vaccination reduced risk. The logistic risk model yielded an AUC of 0.87 (95% CI 0.81-0.94).

The TE rate in pregnant women is largely determined by the severity of the disease. In asymptomatic or mild cases, other factors outweigh TE risk, while severe COVID-19 requiring ICU admission poses a high TE risk despite prophylaxis.

The HLA system is a crucial immune response component against infectious agents, including SARS-CoV-2. Certain polymorphisms may impart varying levels of protection or vulnerability to COVID-19. This research aims to understand the possible relationship between HLA polymorphisms and the susceptibility to COVID-19 and its severity. We recruited 290 hospitalised Iranian COVID-19 patients (130 severe and 160 moderate). Using PCR-SSP methods, we conducted a detailed analysis of polymorphisms in HLA class I (HLA-A, HLA-B, and HLA-C) and II (HLA-DRB1 and HLA-DQB1) molecules at low resolution. The study found that certain HLA alleles, including HLA-B*49, HLA-B*52, HLA-C*12, HLA-DRB1*04, and HLA-DQB1*05, were associated with disease susceptibility. Additionally, HLA-A*23, DRB1*10, and DRB1*13 were indicators of disease severity. The study also noted that individuals carrying the HLA-A*23 allele showed a significant decrease in lymphocyte levels and an elevated likelihood of developing thrombosis. We hypothesise that a maladaptive immune response may occur based on these findings. This might be due to the strong affinity of the HLA-A*23 allele group for presenting a wide range of SARS-CoV-2 peptides. Such a presentation possibly leads to a cytokine storm, followed by lymphocyte apoptosis and an increase in platelet count.

Therapeutic plasma exchange (TPE) is the primary intervention for treating symptomatic hyperviscosity from hypergammaglobulinemia, yet its efficacy for treating hyperviscosity related to hyperfibrinogenemia is unclear.

Define the safety and efficacy of TPE for critically ill COVID-19 patients with elevated blood viscosity from hyperfibrinogenemia.

We performed a prospective randomized controlled trial in critically ill COVID-19 patients in a single US healthcare system. Patients with hyperfibrinogenemia (>800 mg/dL) or elevated plasma viscosity (2.3-3.5 centipoise [cP]) were randomized to receive TPE on 2 consecutive days or continued standard of care (SOC).

Twenty participants were enrolled, with 10 receiving TPE and 10 receiving SOC alone. Mean (±SEM) plasma viscosity decreased significantly from 2.35 cP (±0.12) to 1.61 cP (±0.03) in the TPE group and was unchanged in the SOC group (2.47 cP [±0.11] to 2.47 cP [±0.15]). Mean fibrinogen decreased from 934.0 mg/dL (±25.1) to 359.1 mg/dL (±22.5) after TPE vs from 859.6 mg/dL (±57.6) to 807.3 mg/dL (±63.1) in SOC. There was no significant difference in 28-day all-cause mortality between groups, with 2 deaths in the TPE cohort and 5 deaths in the SOC cohort (P = .13). No serious safety events related to TPE were reported. TPE significantly decreased biomarkers of inflammation (erythrocyte sedimentation rate and C-reactive protein) and endothelial activation (von Willebrand factor and factor VIII) but not hemostatic activation (prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) or immunoglobulin (IgG and IgM) levels.

TPE is safe and effective for normalizing elevated blood viscosity from hyperfibrinogenemia in COVID-19 patients. Additional studies are needed to determine the impact of TPE on overall patient outcomes, including in those with non-COVID-19 conditions associated with hyperfibrinogenemia.

This study compared the efficacy of therapeutic anticoagulation guided by anti-Xa levels vs. a D-dimer-based protocol in ICU patients with COVID-19. Given the heightened risk of thrombosis despite anticoagulation therapy in some cases, we hypothesised that anti-Xa measurement improves anticoagulation effectiveness and clinical outcomes in this population. We retrospectively analysed data from ICU patients at COVID Hospital Karaburma between April 2020 and December 2021. The primary outcome was the incidence of failed noninvasive ventilation necessitating intubation. Secondary endpoints included mortality rates, thromboembolic and bleeding complications, and anticoagulation effectiveness assessed by antifactor Xa activity. The analysis included 395 patients - 137 in the anti-Xa group and 258 in the D-dimer group. The D-dimer group showed a higher rate of failed noninvasive ventilation requiring intubation (65.7% vs. 50%, P  = 0.009). The overall mortality was 48.3%, significantly higher in the D-dimer group (52.7%) compared to the anti-Xa group (40.1%, P  = 0.02). Thromboembolic complications were lower in the anti-Xa group (2.9%) than in the D-dimer group (9.7%, P  = 0.014), with no significant difference in bleeding. Following the first LMWH administration, 70.8% of patients had anti-Xa levels below the therapeutic and 11.7% below the prophylactic range. Anti-Xa-guided anticoagulation improves survival and reduces thromboembolic complications compared to D-dimer-based treatment without increasing bleeding risk. This study highlights the potential of the anti-Xa assay in managing anticoagulation in critically ill COVID-19 patients. Our findings provide a foundation for future research on using anti-Xa measurements as a guiding tool to optimise anticoagulation therapy in other critically ill populations.

The global pandemic of coronavirus disease 2019 (COVID-19) represented a major public health concern. Growing evidence shows that plasma of COVID-19 patients contains large numbers of circulating extracellular vesicles (cEVs) that correlate with disease severity and recovery. In this study, we sought to characterize the longitudinal cEV signature in critically ill COVID-19 patients during hospitalization and its relation to mortality risk.

cEVs were quantitatively and phenotypically analysed in hospitalized non-surviving COVID-19 patients at baseline (n = 42) and before exitus (n = 40) and in 40 healthy volunteers as a reference group by high sensitivity nano flow cytometry using specific markers for parental cell sources and activation.

Levels of cEV subtypes differed between patients with severe COVID-19 and healthy subjects, specifically those from platelets and endothelial, inflammatory and viral infected cells, which associate to high mortality risk. In the longitudinal analysis from baseline to the time point immediately preceding death, no changes were found for platelet, pan-leukocyte, and lung epithelial cell-shed cEVs, while endothelial cell releases of EVs (eEVs) significantly differed. Vascular endothelial growth factor receptor 2-positive eEVs were significantly increased before death compared to admission whereas endoglin and E-selectin-containing eEVs did not change. Conversely, lymphocyte (ℓEV), monocyte, macrophage, pericyte and progenitor cell-derived cEVs displayed significant reductions before exitus. Noteworthy, levels of CD45+/CD3+-ℓEVs were significantly associated to the patient's survival time.

An evolving cEV profile able to discriminate prompt risk of death during hospitalization has been defined suggesting a role for circulating and vascular cell-derived EVs in COVID-19 pathogenesis.

The world is currently grappling with the potentially life-threatening coronavirus disease 2019 (COVID-19), marking it as the most severe health crisis in the modern era. COVID-19 has led to a pandemic, with the World Health Organization (WHO) predicting that individuals with diabetes are at a higher risk of contracting the virus compared to the general population. This review aims to provide a practical summary of the long-term impacts of COVID-19 on patients with diabetes. Specifically, it focuses on the effects of SARS-CoV-2 on different types of diabetic patients, the associated mortality rate, the underlying mechanisms, related complications, and the role of vitamin D and zinc in therapeutic and preventive approaches.

Relevant literature was identified through searches on PubMed, Web of Science, and Science Direct in English, up to April 2023.

COVID-19 can lead to distressing symptoms and pose a significant challenge for individuals living with diabetes. Older individuals and those with pre-existing conditions such as diabetes, coronary illness, and asthma are more susceptible to COVID-19 infection. Managing COVID-19 in individuals with diabetes presents challenges, as it not only complicates the fight against the infection but also potentially prolongs the recovery time. Moreover, the virus may thrive in individuals with high blood glucose levels. Various therapeutic approaches, including antidiabetic drugs, are available to help prevent COVID-19 in diabetic patients.

Diabetes increases the morbidity and mortality risk for patients with COVID-19. Efforts are globally underway to explore therapeutic interventions aimed at reducing the impact of diabetes on COVID-19.

One of the most serious complications of coronary artery stenting is restenosis and in-stent thrombosis; their prevalence can reach 20-25%. Stent thrombosis can be acute (up to 24 hours), subacute (24 hours to 30 days), late (30 days to 1 year), and very late (> 1 year after previous stenting). In the patients with COVID-19 in intensive care units, the proportion of those with elevated troponin levels reached 25%.

Evaluation of the association between COVID-19 and the development of in-stent thrombosis and restenosis of the coronary arteries based on the analysis of clinical cases and case series.

We searched the PubMed and Scopus databases for relevant case reports and case series of stent restenosis and in-stent thrombosis associated with coronavirus infection (CVI) published between 2020 and the present. Thirty-eight full-text publications were screened and manually checked for analysis. We found 10 publications describing cases of thrombosis and restenosis of stents associated with coronavirus infection, of which only 2 were case series. In total, we analyzed 22 cases.

In the structure of in-stent restenosis and thrombosis, 59.1% were very late, 9.1% were late; 18.2% were considered subacute events, and 13.6% were acute events. All cases were angiographically confirmed. The main location of restenosis or thrombosis was the left coronary artery (LAD) (51.1%), thrombosis of the right coronary artery (RCA) occurred in 27.3%, and location in circumflex artery was in 22.7%. All patients had COVID-19 confirmed by a PCR test or the presence of immunoglobulins G and M. In fourteen patients (54.5%), an X-ray examination showed the presence of bilateral polysegmental infiltration.

Analysis of publications demonstrates the association between restenosis and in-stent thrombosis in patients with coronary arteries disease (CAD) and coronavirus infection.

COVID-19-associated acute-respiratory distress syndrome (C-ARDS) results from a direct viral injury associated with host excessive innate immune response mainly affecting the lungs. However, cytokine profile in the lung compartment of C-ARDS patients has not been widely studied, nor compared to non-COVID related ARDS (NC-ARDS).

To evaluate caspase-1 activation, IL-1 signature, and other inflammatory cytokine pathways associated with tissue damage using post-mortem lung tissues, bronchoalveolar lavage fluids (BALF), and serum across the spectrum of COVID-19 severity.

Histological features were described and activated-caspase-1 labeling was performed in 40 post-mortem biopsies. Inflammatory cytokines were quantified in BALF and serum from 19 steroid-treated-C-ARDSand compared to 19 NC-ARDS. Cytokine concentrations were also measured in serum from 128 COVID-19 patients at different severity stages.

Typical "diffuse alveolar damage" in lung biopsies were associated with activated caspase-1 expression and vascular lesions. Soluble Caspase-1p20, IL-1β, IL-1Ra, IL-6 and at lower level IFNγ and CXCL-10, were highly elevated in BALF from steroid-treated-C-ARDS as well as in NC-ARDS. IL-1β appeared concentrated in BALF, whereas circulating IL-6 and IL-1Ra concentrations were comparable to those in BALF and correlated with severity. TNFα, TNFR1 and CXCL8 however, were significantly higher in NC-ARDS compared to C-ARDS, treated by steroid.

In the lungs of C-ARDS, both caspase-1 activation with a predominant IL-1β/IL-6 signature and IFNγ -associated chemokines are elevated despite steroid treatment. These pathways may be specifically targeted in ARDS to improve response to treatment and to limit alveolar and vascular lung damage.

In coronary microembolization, inflammatory cell infiltration, patchy necrosis, and extensive intra-myocardial hemorrhage are dominant, which induce myocardial dysfunction with clinical symptoms of chronic ischemic cardiomyopathy. Microembolization can lead to obstruction of the coronary microvessels and result in the micro-infarction of the heart. The inflammation and elevated expression of the tumor necrosis factor in cardiomyocytes and the activation of extracellular ERK are involved in initiating the inflammatory response mechanism. The PI3K/Akt signaling pathway is the enriched pathway, and for controlling, inhibition of PI3K/Akt is necessary. Furthermore, the release of cytokines and the activation of inflammasomes contribute to the enhancement of vascular permeability, which results in edema within the myocardium. The immune response and inflammation represent the primary triggers in this process. The ability to control immune response and inflammation reactions may lead to the development of new therapies for microembolization.

SARS-CoV-2 (COVID) induces systemic thrombotic complications including acute ischemic stroke. In this case series, we report markers of inflammation, coagulation factors including von Willebrand factor antigen, and rotational thromboelastometry (ROTEM) data.

Retrospective case series of COVID patients seen at a single comprehensive stroke center between 2020-2022. For patients undergoing mechanical thrombectomy (MT), ROTEM data was collected during the procedure and analyzed on ROTEM delta system.

Fifteen patients (33.3% female) median age 65-years-old presented with COVID and acute ischemic stroke. Thirteen had LVO. The mean NIHSS was 15 (range 0-35) on admission and 18 (0-42) at discharge. Most were cryptogenic (N=7, 46.7%), followed by cardioembolic (N=6, 40%) and large artery-to-artery embolization (N=2, 13.3%). mRS was < 3 in 8 (53%) patients at discharge. None of the patients were on anticoagulation, and five were on antiplatelet therapy pre-hospitalization. Seven received thrombolytics with alteplase (tPA), and 10 had MT. Baseline platelet count was 102 K/uL (range 102-291 K/uL). vWF was measured in 12 patients, all elevated, with seven having levels >400 (180%). ROTEM data was collected in six patients. Three who received tPA had abnormal EXTEM and FIBTEM data (CT extem > 85secs, A10 EXTEM < 45mm, and A10 FIBTEM < 10mm). Notably, INTEM (CT INTEM >208secs) was abnormal in five of the six patients, two of whom did not receive tPA.

Elevated vWF antigen levels with abnormal ROTEM data suggests that COVID induces changes in the clotting cascade. More robust research is needed to investigate these findings. Thrombolytics, MT, and antiplatelet agents should be utilized to treat COVID-related ischemic stroke based on current clinical guidelines.

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.

Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease.

To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients.

A Literature search was performed on LitCovid PubMed, WHO, and Scopus databases from inception (December 2019) till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19. The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants. Secondary outcomes included COVID-19 disease severity, in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection, and mortality. The random effects models were used to calculate crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs).

Forty-six observational studies met our inclusion criteria. The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk [n = 43851, 9 studies, odds ratio (OR)= 0.67 (0.22, 2.07); P = 0.49; I 2 = 95%]. The association between prior anticoagulation and disease severity was non-significant [n = 186782; 22 studies, OR = 1.08 (0.78, 1.49); P = 0.64; I 2 = 89%]. However, pre-hospital anticoagulation significantly increased all-cause mortality risk [n = 207292; 35 studies, OR = 1.72 (1.37, 2.17); P < 0.00001; I 2 = 93%]. Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk [aOR = 0.87 (0.42, 1.80); P = 0.71], mortality [aOR = 0.94 (0.84, 1.05); P = 0.31], and disease severity [aOR = 0.96 (0.72, 1.26); P = 0.76].

Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower disease severity in COVID-19 patients.

Recent research has shown that there is a link between the trend of cardiovascular disease (CVD), chronic symptoms of SARS-CoV-2 (COVID-19), and medical nutrition therapy. Making positive changes to an individual's lifestyle can help to reduce the symptoms that follow exposure to CVD and COVID-19. Sustainable nutrition and lifestyle changes can positively impact an individual's health. Studies have considered the risk factors associated with the disease, medical history, the link between nutrition and peripheral vascular disease (PVD), symptom management, and the interrelationship between nutrition, COVID-19, and PVD. One study has demonstrated that Western Dietary intake can boost the innate immune system while suppressing humoral response, causing chronic inflammation and poor host defense against viruses. However, further investigation is needed to confirm. Patients with PVD and COVID-19 have experienced a reduction in side effects when prescribed a regimen of medical nutrition therapy, heart-healthy diets, and adequate physical activity before and after symptoms of both diseases appear. This approach has proven to be a protective factor during the combination of both illnesses. Our findings indicate that balanced diet and lifestyle are essential in supporting an optimal immune system that can reduce the risk of virus load in individuals at risk of infection and symptoms from COVID-19 and PVD.

In addition to the respiratory symptoms associated with COVID-19, the disease has consistently been linked to many autoimmune diseases such as systemic lupus erythematous and antiphospholipid syndrome (APS). APS in particular was of paramount significance due to its devastating clinical sequela. In fact, the hypercoagulable state seen in patients with acute COVID-19 and the critical role of anticoagulant treatment in affected individuals shed light on the possible relatedness between APS and COVID-19. Moreover, the role of autoimmunity in the assumed association is not less important especially with the accumulated data available regarding the autoimmunity-triggering effect of SARS-CoV-2 infection. This is furtherly strengthened at the time patients with COVID-19 manifested antiphospholipid antibodies of different types following infection. Additionally, the severe form of the APS spectrum, catastrophic APS (CAPS), was shown to have overlapping characteristics with severe COVID-19 such as cytokine storm and multi-organ failure. Interestingly, COVID vaccine-induced autoimmune phenomena described in the medical literature have pointed to an association with APS. Whether the antiphospholipid antibodies were present or de novo, COVID vaccine-induced vascular thrombosis in certain individuals necessitates further investigations regarding the possible mechanisms involved. In our current paper, we aimed to focus on the associations mentioned, their implications, importance, and consequences.

Brain arteriovenous malformations (AVMs) are usually asymptomatic. They can cause intense pain or bleeding or lead to other serious medical problems. We present a rare case of a woman who presented with a severe headache and was brought to the emergency service for an intracerebral hemorrhage due to a ruptured AVM. During the surgery, a sellar mass was identified that was also resected. AVM showed vasculitis, endarteritis, endothelial damage, leukocyte plug, and damage to the vessel wall with fragmentation of the collagen and actin filaments. The sellar mass showed a non-functioning pituitary adenoma with hemorrhagic foci and necrosis as well as a proteinaceous vs. lipid material deposition with minimal vascular changes such as endothelial hyperplasia with minimal vasculitis and hyperplasia of reticular stellate cells, with positive glial fibrillary acidic protein (GFAP), which expressed low expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), IL6, IL10, IL17, tumor necrosis factor-alpha (TNFa), HIF1a, factor VIII (FVIII), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and VEGF receptor 2 (VEGFR2). The patient's polymerase chain reaction COVID-19 test was positive, and she died three days after the surgery procedure. In our knowledge of COVID-19 brain lesions and in the literature review, this was a rare case of a double pathology associated with COVID-19 infection characterized by rupture of the AVM with hemorrhages and brain infarcts associated with endarteritis, vessel wall injuries, and pituitary apoplexy.

Laboratory markers like lymphopenia, thrombocytopenia, elevated D-dimer, and C-reactive protein (CRP) predict worse outcomes in coronavirus disease 2019 (COVID-19). However, a comprehensive analysis of hematologic and coagulation parameter alterations based on fever status is lacking.

This retrospective study analyzed 300 COVID-19 patients hospitalized from March to December 2020. Demographic, clinical, and laboratory data were extracted from electronic medical records. Patients were stratified into fever (n = 200) and no fever (n = 100) groups. Hematologic, coagulation, and inflammatory markers were compared between groups using appropriate statistical tests. Multivariate regression identified independent predictors of fever.

Fever was associated with leukocytosis, neutrophilia, lymphopenia, thrombocytopenia, elevated CRP, D-dimer, procalcitonin, interleukin-6, neutrophil to lymphocyte ratio (NLR), and ferritin compared to no fever (all P < 0.05). D-dimer (r = 0.42), CRP (r = 0.52), NLR (r = 0.48), and interleukin-6 (r = 0.46) demonstrated the strongest correlation with fever (P < 0.001). High D-dimer >1000 ng/mL (adjusted odds ratio 2.7), CRP >100 mg/L (3.1), lymphopenia <1.0 × 109/L (2.8), NLR >4 (2.9), and thrombocytopenia <150 × 109/L (2.7) were significant independent predictors of fever status (P < 0.005). These parameters had moderate sensitivity (40-60%) and high specificity (74-88%) for discriminating febrile patients with AUC of 0.85.

Marked alterations in hematologic, coagulation, and inflammatory markers occur in COVID-19 based on fever. Routine laboratory parameters can facilitate diagnosis and risk stratification.

Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (≈2 Euro/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.

In this paper, we propose a model that connects two standard inflammatory responses to viral infection, namely, elevation of fibrinogen and the lipid drop shower, to the initiation of non-thrombin-generated clot formation. In order to understand the molecular basis for the formation of non-thrombin-generated clots following viral infection, human epithelial and Madin-Darby Canine Kidney (MDCK, epithelial) cells were infected with H1N1, OC43, and adenovirus, and conditioned media was collected, which was later used to treat human umbilical vein endothelial cells and human lung microvascular endothelial cells. After direct infection or after exposure to conditioned media from infected cells, tissue surfaces of both epithelial and endothelial cells, exposed to 8 mg/mL fibrinogen, were observed to initiate fibrillogenesis in the absence of thrombin. No fibers were observed after direct viral exposure of the endothelium or when the epithelium cells were exposed to SARS-CoV-2 isolated spike proteins. Heating the conditioned media to 60 °C had no effect on fibrillogenesis, indicating that the effect was not enzymatic but rather associated with relatively thermally stable inflammatory factors released soon after viral infection. Spontaneous fibrillogenesis had previously been reported and interpreted as being due to the release of the alpha C domains due to strong interactions of the interior of the fibrinogen molecule in contact with hydrophobic material surfaces rather than cleavage of the fibrinopeptides. Contact angle goniometry and immunohistochemistry were used to demonstrate that the lipids produced within the epithelium and released in the conditioned media, probably after the death of infected epithelial cells, formed a hydrophobic residue responsible for fibrillogenesis. Hence, the standard inflammatory response constitutes the ideal conditions for surface-initiated clot formation.

Background: Severe coagulation abnormalities are common in patients with COVID-19 infection. We aimed to investigate the relationship between pro-inflammatory cytokines and coagulation parameters concerning socio-demographic, clinical, and laboratory characteristics. Methods: Our study included patients hospitalized during the second wave of COVID-19 in the Republic of Serbia. We collected socio-demographic, clinical, and blood-sample data for all patients. Cytokine levels were measured using flow cytometry. Results: We analyzed data from 113 COVID-19 patients with an average age of 58.15 years, of whom 79 (69.9%) were male. Longer duration of COVID-19 symptoms before hospitalization (B = 69.672; p = 0.002) and use of meropenem (B = 1237.220; p = 0.014) were predictive of higher D-dimer values. Among cytokines, higher IL-5 values significantly predicted higher INR values (B = 0.152; p = 0.040) and longer prothrombin times (B = 0.412; p = 0.043), and higher IL-6 (B = 0.137; p = 0.003) predicted longer prothrombin times. Lower IL-17F concentrations at admission (B = 0.024; p = 0.050) were predictive of higher INR values, and lower IFN-γ values (B = -0.306; p = 0.017) were predictive of higher aPTT values. Conclusions: Our findings indicate a significant correlation between pro-inflammatory cytokines and coagulation-related parameters. Factors such as the patient's level of education, gender, oxygen-therapy use, symptom duration before hospitalization, meropenem use, and serum concentrations of IL-5, IL-6, IL-17F, and IFN-γ were associated with worse coagulation-related parameters.

Despite high global vaccination coverage, it remains unclear how vaccination and anti-SARS-CoV-2 antibodies affect immune responses and inflammation levels in patients with COVID-19. It is further unclear whether the inflammatory response differs depending on antibody levels and whether the combination of antibody and inflammation levels in COVID-19 patients affects mortality rates.

We conducted a prospective multicenter cohort study that included 1031 hospitalized COVID-19 patients from five hospitals. Anti-SARS-CoV-2-spike antibodies, interleukin-6 (IL6), and CRP were measured on hospital admission. The prespecified endpoint was all-cause in-hospital mortality.

We observed significantly lower levels of CRP (P<0.001) and IL6 (P<0.001) in patients with antibody levels above 1200 BAU/ml. After adjusting for potential confounders, patients with high levels of inflammatory markers (CRP>6 mg/dl or IL6>100 pg/ml) combined with low levels of anti-SARS-CoV-2-spike antibodies (<1200 BAU/ml) were approximately 8 times more likely to die than patients with low inflammatory responses and high antibody levels (CRP: aHR 7.973, 95% CI 2.744-23.169, P<0.001; IL6: aHR 8.973, 95% CI 3.549-22.688, P<0.001).

Hospitalized COVID-19 patients presenting with high inflammatory markers and low antibody levels exhibited the highest mortality risks. Higher antibody levels are associated with lower levels of inflammation in hospitalized COVID-19 patients.

Spinal cord ischemia is a rare but ominous clinical situation with high levels of disability. There are emerging reports on COVID-19 and spinal cord ischemic events.

To investigate the cardinal manifestations of SARS-CoV-2 associated spinal cord ischemia, review treatment paradigms, and follow outcomes.

A systematic review.

The current study was conducted under Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The authors searched PubMed, Scopus, Web of Science, and Google Scholar for studies published up to February 12, 2023, on spinal cord ischemia and SARS-CoV-2 infection. Data on patient demographics, study methods, medical records, interventions, and outcomes were extracted from eligible articles. For each data set, the authors performed pooled estimates examining 3 factors of interest, which were (1) predisposing factors (2) treatment regimens, and (3) neurological rehabilitation outcomes. Neurological status was reported as the American Spinal Injury Association (ASIA) impairment scale reported by data sets.

Six data sets were identified. The mean age of the study population was 50 years old, with 66.6% male predominance. Sixty-six percent of the patients had severe COVID-19. Five data sets reported preexisting coagulopathy. ASIA A and B were the most prevalent primary neurological status (80%). The mean interval between COVID-19 and the first neurological deficit was 13 days. Anterior spinal artery lesions were the most prevalent ischemic pattern. The most common treatment regimens were heparin and steroid therapy. Physical rehabilitation showed poor functional outcomes.

SARS-CoV-2 is associated with spinal cord ischemia through multiple neuropathological mechanisms. Proper coagulation profile control and aggressive rehabilitation may play a promising role in the prevention and recovery of spinal cord infarction in SARS-CoV-2 patients.

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly known as 2019-nCoV. Numerous cellular and biochemical issues arise after COVID-19 infection. The severe inflammation that is caused by a number of cytokines appears to be one of the key hallmarks of COVID-19. Additionally, people with severe COVID-19 have coagulopathy and fulminant thrombotic events. We briefly reviewed the COVID-19 disease at the beginning of this paper. The inflammation and coagulation markers and their alterations in COVID-19 illness are briefly discussed in the parts that follow. Next, we talked about NETosis, which is a crucial relationship between coagulation and inflammation. In the end, we mentioned the two-way relationship between inflammation and coagulation, as well as the factors involved in it. We suggest that inflammation and coagulation are integrated systems in COVID-19 that act on each other in such a way that not only inflammation can activate coagulation but also coagulation can activate inflammation.

In the present study, we aimed to evaluate coronavirus disease 2019 (COVID-19) infection effects on fetal diaphragm thickness and diaphragmatic excursion, which together show the quality of diaphragmatic contractions.

One hundred and ninety-two pregnant women were included in this prospective case-control study. Patients were divided into four groups according to their COVID-19 infection history in their second or third trimester: hospitalized COVID-19-infected pregnant women group (n = 48), outpatient COVID-19-infected pregnant women group (n = 48), common cold (COVID-19 polymerase chain reaction negative) pregnant women group (n = 48), and noninfected healthy controls (n = 48). The number of patients was determined by power analysis following the pilot study. All participants underwent an ultrasound examination to determine fetal diaphragm parameters at 32 to 37 weeks of gestation.

Demographic characteristics were similar among the four groups. The gestational age at ultrasound examination and gestational age at delivery were similar among the groups. Neonatal intensive care unit (NICU) admission rate was significantly higher in the hospitalized COVID-19-infected pregnant women group than the other groups. The fetal diaphragm thickness during inspiration and expiration, and fetal costophrenic angles at inspiration and expiration were similar among the groups. Fetal diaphragmatic excursion was significantly decreased in the hospitalized COVID-19-infected pregnant women group compared with the other groups.

Our results indicated that moderate maternal COVID-19 infection decreased fetal diaphragmatic excursion, and ultrasonographic evaluation of fetal diaphragmatic excursion before delivery can provide critical information to predict whether infants will require NICU admission.

· Diaphragm ultrasound as a new technique for characterizing the diaphragm's structure and function.. · Fetal diaphragmatic excursion is decreased in the presence of moderate COVID-19 infection.. · Ultrasonographic evaluation of fetal diaphragmatic excursion provides critical information to predict NICU admission..

Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities and increased risk for venous and arterial thrombi. This study aimed to evaluate D-dimer levels and lupus anticoagulant (LAC) positivity in pregnant individuals with and without Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

This was a prospective cohort study of pregnant individuals delivering at a single academic institution from April 2020 to March 2022. Individuals with a positive SARS-CoV-2 result during pregnancy were compared with a convenience sample of those without a positive SARS-CoV-2 result. For individuals with SARS-CoV-2 infection, severity was assessed based on the National Institutes of Health classification system. The primary outcome was D-dimer level measured during delivery admission. The secondary outcomes were LAC positivity and thromboembolic events. Outcomes were compared between individuals with and without a positive SARS-CoV-2 result, and further by disease severity.

Of 98 participants, 77 (78.6%) were SARS-CoV-2 positive during pregnancy. Among individuals with SARS-CoV-2 infection, severity was asymptomatic in 20 (26.0%), mild in 13 (16.9%), moderate in 4 (5.2%), severe in 38 (49.4%), and critical in 2 (2.6%). The D-dimer concentration at delivery did not significantly differ between those with a SARS-CoV-2 positive result compared with those without (mean 2.03 µg/mL [95% confidence interval {CI} 1.72-2.40] vs. 2.37 µg/mL [95% CI 1.65-3.40]; p = 0.43). Three individuals (4%) with SARS-CoV-2 infection and none (0%) without infection were LAC positive (p = 0.59). There were no clinically apparent thromboses in either group. D-dimer concentrations and LAC positive results did not differ by COVID-19 severity.

Thrombotic markers did not differ in pregnant individuals by SARS-CoV-2 infection; however, high rates of LAC positivity were detected.

· Thrombotic markers did not differ in pregnant individuals by SARS-CoV-2 infection.. · Higher than expected rates of LAC positivity were detected.. · There were no clinically apparent thromboses..

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.

The global outbreak of coronavirus disease 2019 (COVID-19) presents numerous obstacles for healthcare professionals. The present study aimed to evaluate and compare the role of serum biomarkers like- C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimers in the severity of COVID-19 infection.

A cross-sectional, observational retrospective pilot study was conducted in Udaipur, Rajasthan, wherein data was collected from 250 subjects, out of which, data of 100 subjects were included as per the inclusion criteria. The data was recorded retrospectively among the health professionals via Google Forms in Udaipur, Rajasthan.

There were 1 (1%), 3 (3%), 31 (31%) and 65 (65%) participants with minor elevation (0.3-1.0), moderate elevation (1-10), marked elevation (10-50) and severe elevation (>50) of CRP respectively. The difference between the groups was statistically highly significant with a significantly higher number of study participants with a severe elevation of CRP levels (χ2 = 107.84, P < 0.001). The results showed that there was a significant difference between the groups with IL6 in 0-7 range while 96 (96%) study participants had >7 IL6, and the difference was statistically highly significant (2 = 84.640, P 0.001).

In conclusion, the existing body of research indicates a discernible correlation between COVID-19 infection and the fluctuation of biomarker levels. This supplement has the potential to be utilised in clinical practice as a means of informing treatment decisions and determining the necessity of admission to the intensive care unit (ICU).

Coronavirus disease 2019 (COVID-19) predominantly causes respiratory symptoms. However, a rare segment of patients recovering from COVID-19 may develop gastrointestinal (GI) symptoms. We describe a case of a female who presented with symptoms suggestive of refractory gastroesophageal reflux disease (GERD) for 18 months following COVID-19 infection. Her symptoms included epigastric and chest pain, coughing, and vomiting. Upper endoscopy and 24-hour pH monitoring were negative. Following hospital admission due to worsening symptoms, she was diagnosed with chronic pulmonary embolism (PE) presumed to be related to COVID-19. Her reflux symptoms resolved within two days of the initiation of anticoagulation. Our findings suggest that chronic PE should be considered in patients presenting with GERD refractory to treatment following COVID-19 infection. Generally, as COVID-19 and its sequelae may masquerade as GI conditions, they should be on the differential diagnosis, especially in the post-pandemic era when routine testing has significantly declined.

This study, which included patients over the age of 18 who were diagnosed with coronavirus disease 2019 (COVID-19) in the emergency clinic, aims to determine the relationship between coagulation parameters and mortality. Epidemiologic data such as age, gender, medical history, vital parameters at emergency department admission, clinical findings, coagulation parameters such as d-dimer, prothrombin time (PT), active partial thromboplastin time (aPTT), international normalized ration (INR), fibrinogen, and platelet were evaluated. Patients with positive computerized tomography (CT) findings and positive polymerase chain reaction (PCR) together were included in the study. It was revealed that d-dimer, fibrinogen, INR, and PT values were higher in the elderly group. It was shown that there was a significant relationship between hospitalization days (ward or intensive care unit) and d-dimer levels. It was observed that d-dimer, fibrinogen elevation was significantly associated with prognosis by increasing mortality, and that platelet and aPTT values were also associated with prognosis and were lower in the mortality group. On the other hand, in receiver operating characteristic (ROC) analysis, the sensitivity and specificity data were 80.3%/80.0% for d-dimer, 70.5%/72.2% for fibrinogen, 58.2%/59.4% for aPTT, and 59.7%/59.2% for platelet, respectively. The overall classification success was 88.6% and mortality prediction success was 37.7% in the regression model of some coagulation parameters (d-dimer, fibrinogen, aPTT, and platelet) which were effective on prognosis. In conclusion, it was determined that d-dimer, fibrinogen, aPTT, and platelet parameters were directly associated with mortality and when these coagulation parameters were used together with the clinical, vital, and demographic data of the patients, the success of mortality prediction increased significantly.

Postacute sequelae of COVID-19 (PASC), also referred to as "Long COVID", sometimes follows COVID-19, a disease caused by SARS-CoV-2. Although SARS-CoV-2 is well known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. Our objective was to evaluate platelet function and thrombotic potential in patients following recovery from SARS-CoV-2, but with clear symptoms of patients with PASC.

patients with PASC and matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by light transmission aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under shear stress conditions.

A mild increase in platelet aggregation in patients with PASC through the thromboxane receptor was observed, and platelet activation through the glycoprotein VI (GPVI) receptor was decreased in patients with PASC compared to age- and sex-matched healthy controls. Thrombosis under shear conditions as well as Factor Xa activity were reduced in patients with PASC. Plasma from patients with PASC was an extremely potent activator of washed, healthy platelets - a phenomenon not observed when stimulating healthy platelets after incubation with plasma from healthy individuals.

patients with PASC show dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating molecule that promotes thrombosis. A hitherto undescribed protective response appears to exist in patients with PASC to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.

Microglial cells, the immune cells of the central nervous system, are key elements regulating brain development and brain health. These cells are fully responsive to stressors, microenvironmental alterations and are actively involved in the construction of neural circuits in children and the ability to undergo full experience-dependent plasticity in adults. Since neuroinflammation is a known key element in the pathogenesis of COVID-19, one might expect the dysregulation of microglial function to severely impact both functional and structural plasticity, leading to the cognitive sequelae that appear in the pathogenesis of Long COVID. Therefore, understanding this complex scenario is mandatory for establishing the possible molecular mechanisms related to these symptoms. In the present review, we will discuss Long COVID and its association with reduced levels of BDNF, altered crosstalk between circulating immune cells and microglia, increased levels of inflammasomes, cytokines and chemokines, as well as the alterations in signaling pathways that impact neural synaptic remodeling and plasticity, such as fractalkines, the complement system, the expression of SIRPα and CD47 molecules and altered matrix remodeling. Together, these complex mechanisms may help us understand consequences of Long COVID for brain development and its association with altered brain plasticity, impacting learning disabilities, neurodevelopmental disorders, as well as cognitive decline in adults.

Thromboembolism is reported to be up to 27% in COVID-19 patients due to SARS-CoV-2 infection. Dysregulated systemic inflammation and various patient traits play a vital role in thrombosis progression.

To assess odds and associated factors for thrombosis development among Lebanese COVID-19 patients.

This was a case-control retrospective study conducted in January-May 2021. Patients infected with COVID-19 and developed thrombosis were classified as cases and patients who were thrombosis-free identified as control. A questionnaire assessed socio-demographics, clinical parameters, and WHO COVID-19 disease severity.

Among 267 patients, 26 (9.7%) developed thrombosis and the majority of thrombosis 34.6% was myocardial infarction, and the least (3.8%) was for catheter-related thrombosis. Results showed that the risk of thrombosis development is higher in patients with previous thromboembolic event (OR = 9.160) and previous intake of anti-hypertensive medications at home (OR = 3.116). However, females (OR = 0.330; CI: 0.118-0.925), intake of anticoagulants during hospital admission (OR = 0.126; CI: 0.053-0.300) and non-severe COVID-19 were at lower thrombosis risk (OR = 0.273). Patients who developed thromboembolic events had longer hospital stay (OR = 0.077).

Patients with COVID-19 and thromboembolism were at higher risk of mortality as compared to patients with COVID-19 but without thromboembolism. The use of anticoagulants significantly reduced the risk for thromboembolism.

The range of clinical manifestations associated with the infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encompasses a broad spectrum, ranging from flu-like symptoms to the occurrence of multiple organ failure and death. The severity of the coronavirus disease 2019 (COVID-19) is categorized based on clinical presentation and is divided into three distinct levels of severity identified as non-severe, severe, and critical. Although individuals of all age groups are susceptible to SARS-CoV-2 infection, middle-aged and older adults are more frequently impacted, with the latter being more likely to develop severe illness. Various laboratory characteristics observed in hospitalized COVID-19 patients have been correlated with adverse outcomes. These include elevated levels of D-dimer, liver enzymes, lactate dehydrogenase, C-reactive protein, ferritin, prothrombin time, and troponin, as well as decreased lymphocyte and platelets counts. This review investigated the relationship between baseline clinical characteristics, initial laboratory parameters upon hospital admission, and the severity of illness and mortality rates among COVID-19 patients. Although the COVID-19 pandemic has concluded, understanding the laboratory predictors of virus severity and mortality remains crucial, and examining these predictors can have long-term effects. Such insights can help healthcare systems manage resources more effectively and deliver timely and appropriate care by identifying and targeting high-risk individuals. This knowledge can also help us better prepare for future pandemics. By examining these predictors, we can take steps to protect public health and mitigate the impact of future pandemics.

Several studies have evaluated the possible association between whole blood viscoelastic testing (VET) parameters in patients hospitalized for acute Coronavirus disease 2019 (COVID-19) pneumonia and mortality. A few studies found no significant differences between survivors and non-survivors, though other studies identified potential predictors of COVID-19-related mortality. We conducted a systematic review and meta-analysis of the literature to evaluate the possible association between standard thromboelastometry/graphy parameters and mortality in patients hospitalized for acute COVID-19 pneumonia.

Relevant studies were searched through MEDLINE, EMBASE, and Google Scholar from their inception until 15th June 2023. We aimed to identify any study including: i) adults admitted to intensive care units (ICU) or medicine wards (MW) for acute COVID-19 pneumonia; ii) viscoelastic testing; iii) mortality.

We included 13 studies: nine prospective and four retrospective, 231 (30.4 %) non-survivors and 528 (69.6 %) survivors. Mortality rates ranged from 12.8 % to 67.5 %. The studies using the TEG apparatus found a significant difference in K time in the Kaolin test among survivors vs. non-survivors (mean difference [MD] 0.20, 95 % confidence interval [CI] 0.12, 0.28, I2 0%). The studies using the rotational thromboelastometry apparatus found a significant difference in CT-INTEM (MD -17.14, 95 % CI -29.23, -5.06, I2 0%) and LI60-EXTEM (MD -1.00, 95 % CI -1.00, -1.00, I2 0%) assays among survivors vs. non-survivors.

We identified no specific hypercoagulable or hypocoagulable profile associated with mortality in patients with COVID-19-related pneumonia. Large prospective studies are needed to explore the possible prognostic role of VET in this subset of patients.