ABSTRACT
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.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/complications , COVID-19/virology , COVID-19/pathology , SARS-CoV-2/pathogenicity , Lung/blood supply , Lung/pathology , Lung/virology , Pulmonary Embolism/virology , Pulmonary Embolism/etiology , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/virology , Hypertension, Pulmonary/pathology , Post-Acute COVID-19 Syndrome , Thrombosis/virology , Thrombosis/etiology , Thrombosis/pathologyABSTRACT
Background: Coronavirus 2019 infection (COVID 19) is an ongoing pandemic caused by pathogenic RNA viruses called severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). It has affected people of all ages, with high morbidity and mortality among the elderly and immunocompromised population. Limited information is available on the effects of COVID-19 infection on pregnancy. Aim: To describe the histopathological changes in the placental tissue of SARS-CoV-2 infected term mothers with no comorbidities and to correlate with neonatal outcome. Materials and Methods: This observational study was conducted in the Department of Pathology, KMCH institute of health sciences and research, Coimbatore from May 1, 2020 to November 30, 2020 for 6 months. Placental tissues of all COVID-19-positive term mothers with no comorbidities were included in this study. Histopathological examination of placentae was carried out and clinical data of mothers and newborn babies were obtained from medical records. Results: Histopathological examination of 64 placental tissue of COVID-19 mothers showed predominantly the features of fetal vascular malperfusion like stem villi vasculature thrombus, villous congestion, and avascular villi. No significant correlation was obtained in comparison with parity and symptomatic status of the mothers. However, histopathological changes were more prominent among symptomatic patients. The newborn babies born to these mothers showed no adverse outcome. Conclusion: This study concluded that though COVID-19 infection in normal term pregnant women was associated with increased prevalence of features of fetal vascular malperfusion, there was no significant morbidity in the health status of both COVID-19 mothers and their neonates.
Subject(s)
COVID-19 , Placenta , Pregnancy Complications, Infectious , Placenta/pathology , Placenta/virology , COVID-19/pathology , Humans , Female , Pregnancy , Adult , Chorionic Villi/pathology , Chorionic Villi/virology , Infant, Newborn , Thrombosis/virology , Pregnancy Complications, Infectious/pathology , Pregnancy Complications, Infectious/virologyABSTRACT
COVID-19 infection triggers a heightened inflammatory response which in turn, increases thrombosis and thromboembolism. Microvascular thrombosis has been detected in various tissue beds which may account for some of the multi-system organ dysfunction associated with COVID-19. Additional research is needed to understand which prophylactic and therapeutic drug regimens are best for the prevention and treatment of thrombotic complications of COVID-19.
Subject(s)
COVID-19 , Thromboembolism , Thrombosis , Humans , COVID-19/complications , Thrombosis/drug therapy , Thrombosis/virology , Thromboembolism/drug therapy , Thromboembolism/virologyABSTRACT
Herpes zoster (HZ; shingles) caused by varicella zoster virus reactivation increases stroke risk for up to 1 year after HZ. The underlying mechanisms are unclear, however, the development of stroke distant from the site of zoster (eg, thoracic, lumbar, sacral) that can occur months after resolution of rash points to a long-lasting, virus-induced soluble factor (or factors) that can trigger thrombosis and/or vasculitis. Herein, we investigated the content and contributions of circulating plasma exosomes from HZ and non-HZ patient samples. Compared with non-HZ exosomes, HZ exosomes (1) contained proteins conferring a prothrombotic state to recipient cells and (2) activated platelets leading to the formation of platelet-leukocyte aggregates. Exosomes 3 months after HZ yielded similar results and also triggered cerebrovascular cells to secrete the proinflammatory cytokines, interleukin 6 and 8. These results can potentially change clinical practice through addition of antiplatelet agents for HZ and initiatives to increase HZ vaccine uptake to decrease stroke risk.
Subject(s)
Herpes Zoster , Stroke , Humans , Exosomes , Herpes Zoster/epidemiology , Herpesvirus 3, Human/physiology , Stroke/epidemiology , Risk Assessment , Male , Female , Plasma/cytology , Thrombosis/virologyABSTRACT
We hypothesized that exosomal microRNAs could be implied in the pathogenesis of thromboembolic complications in coronavirus disease 2019 (COVID-19). We isolated circulating exosomes from patients with COVID-19, and then we divided our population in two arms based on the D-dimer level on hospital admission. We observed that exosomal miR-145 and miR-885 significantly correlate with D-dimer levels. Moreover, we demonstrate that human endothelial cells express the main cofactors needed for the internalization of the "Severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), including angiotensin converting enzyme 2, transmembrane protease serine 2, and CD-147. Interestingly, human endothelial cells treated with serum from COVID-19 patients release significantly less miR-145 and miR-885, exhibit increased apoptosis, and display significantly impaired angiogenetic properties compared with cells treated with non-COVID-19 serum. Taken together, our data indicate that exosomal miR-145 and miR-885 are essential in modulating thromboembolic events in COVID-19. SIGNIFICANCE STATEMENT: This work demonstrates for the first time that two specific microRNAs (namely miR-145 and miR-885) contained in circulating exosomes are functionally involved in thromboembolic events in COVID-19. These findings are especially relevant to the general audience when considering the emerging prominence of post-acute sequelae of COVID-19 systemic manifestations known as Long COVID.
Subject(s)
COVID-19 , Exosomes , MicroRNAs , Post-Acute COVID-19 Syndrome , Thrombosis , Humans , COVID-19/complications , Endothelial Cells , MicroRNAs/genetics , MicroRNAs/metabolism , Post-Acute COVID-19 Syndrome/genetics , Post-Acute COVID-19 Syndrome/metabolism , SARS-CoV-2 , Thrombosis/genetics , Thrombosis/metabolism , Thrombosis/virology , Exosomes/metabolismABSTRACT
Although thrombosis frequently occurs in infectious diseases, the coagulopathy associated with COVID-19 has unique characteristics. Compared with bacterial sepsis, COVID-19-associated coagulopathy presents with minimal changes in platelet counts, normal prothrombin times, and increased D-dimer and fibrinogen levels. These differences can be explained by the distinct pathophysiology of the thromboinflammatory responses. In sepsis-induced coagulopathy, leukocytes are primarily responsible for the coagulopathy by expressing tissue factor, releasing neutrophil extracellular traps, multiple procoagulant substances, and systemic endothelial injury that is often associated with vasoplegia and shock. In COVID-19-associated coagulopathy, platelet activation is a major driver of inflammation/thrombogenesis and von Willebrand factor and platelet factor 4 are deeply involved in the pathogenesis. Although the initial responses are localized to the lung, they can spread systemically if the disease is severe. Since the platelets play major roles, arterial thrombosis is not uncommon in COVID-19. Despite platelet activation, platelet count is usually normal at presentation, but sensitive biomarkers including von Willebrand factor activity, soluble P-selectin, and soluble C-type lectin-like receptor-2 are elevated, and they increase as the disease progresses. Although the role of antiplatelet therapy is still unproven, current studies are ongoing to determine its potential effects.
Subject(s)
Blood Coagulation Disorders , COVID-19 , Platelet Activation , Thrombosis , Humans , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/virology , COVID-19/complications , Thrombosis/blood , Thrombosis/virology , von Willebrand Factor/metabolismABSTRACT
Thrombosis is a hallmark of severe COVID-19. Alpha-1-antitrypsin (AAT), an inflammation-inducible serpin with anti-inflammatory, tissue protective and anticoagulant properties may be involved in severe COVID-19 pathophysiology including thrombosis onset. In this study, we examined AAT ability to predict occurrence of thrombosis and in-hospital mortality during COVID-19. To do so, we performed a monocentric cross-sectional study of 137 hospitalized patients with COVID-19 of whom 56 (41%) were critically ill and 33 (22.4%) suffered from thrombosis during hospitalization. We measured AAT and IL-6 plasma levels in all patients and phenotyped AAT in a subset of patients with or without thrombosis paired for age, sex and COVID-19 severity. We observed that AAT levels at admission were higher in both non-survivors and thrombosis patients than in survivors and non-thrombosis patients. AAT: IL-6 ratio was lower in non-survivors and thrombosis patients. In a logistic regression multivariable analysis model adjusted on age, BMI and D-dimer levels, a higher AAT: IL-6 was a protective factor of both in-hospital mortality (Odds ratio, OR: 0.07 95%CI [0.02-0.25], p < 0.001) and thrombosis (OR 0.36 95%CI [0.14-0.82], p = 0.02). AAT phenotyping did not show a higher proportion of AAT abnormal variants in thrombosis patients.Our findings suggest an insufficient production of AAT regarding inflammation intensity during severe COVID-19. AAT appeared as a powerful predictive marker of severity, mortality and thrombosis mirroring the imbalance between harmful inflammation and protective counter-balancing mechanism in COVID-19. Restoring the balance between AAT and inflammation could offer therapeutic opportunities in severe COVID-19.
Subject(s)
COVID-19 , Hospital Mortality , Interleukin-6 , Thrombosis , alpha 1-Antitrypsin , Humans , COVID-19/complications , COVID-19/mortality , Cross-Sectional Studies , Inflammation , Interleukin-6/blood , alpha 1-Antitrypsin/blood , Thrombosis/virologyABSTRACT
BACKGROUND: Coronavirus-induced disease 19 (COVID-19) infects more than three hundred and sixty million patients worldwide, and people with severe symptoms frequently die of acute respiratory distress syndrome (ARDS). Recent studies indicated that excessive neutrophil extracellular traps (NETs) contributed to immunothrombosis, thereby leading to extensive intravascular coagulopathy and multiple organ dysfunction. Thus, understanding the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation would be helpful to reduce thrombosis and prevent ARDS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We incubated SARS-CoV-2 with neutrophils in the presence or absence of platelets to observe NET formation. We further isolated extracellular vesicles from COVID-19 patients' sera (COVID-19-EVs) to examine their ability to induce NET formation. RESULTS: We demonstrated that antagonistic mAbs against anti-CLEC5A mAb and anti-TLR2 mAb can inhibit COVID-19-EVs-induced NET formation, and generated clec5a-/-/tlr2-/- mice to confirm the critical roles of CLEC5A and TLR2 in SARS-CoV-2-induced lung inflammation in vivo. We found that virus-free extracellular COVID-19 EVs induced robust NET formation via Syk-coupled C-type lectin member 5A (CLEC5A) and TLR2. Blockade of CLEC5A inhibited COVID-19 EVs-induced NETosis, and simultaneous blockade of CLEC5A and TLR2 further suppressed SARS-CoV-2-induced NETosis in vitro. Moreover, thromboinflammation was attenuated dramatically in clec5a-/-/tlr2-/- mice. CONCLUSIONS: This study demonstrates that SARS-CoV-2-activated platelets produce EVs to enhance thromboinflammation via CLEC5A and TLR2, and highlight the importance of CLEC5A and TLR2 as therapeutic targets to reduce the risk of ARDS in COVID-19 patients.
Subject(s)
COVID-19 , Lectins, C-Type , Neutrophils , Pneumonia , Respiratory Distress Syndrome , SARS-CoV-2 , Thrombosis , Animals , Blood Platelets/immunology , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/blood , COVID-19/immunology , Humans , Lectins, C-Type/immunology , Mice , Neutrophils/immunology , Neutrophils/pathology , Neutrophils/virology , Pneumonia/immunology , Pneumonia/pathology , Pneumonia/virology , Receptors, Cell Surface , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/virology , SARS-CoV-2/immunology , Thrombosis/blood , Thrombosis/immunology , Thrombosis/virology , Toll-Like Receptor 2/immunologyABSTRACT
Blood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin antimicrobial peptides after SARS-CoV-2 infection and their role in COVID-19 thrombosis formation remain unclear. In the current study, we analyzed coagulation function and found a decrease in thrombin time but an increase in fibrinogen level, prothrombin time, and activated partial thromboplastin time in COVID-19 patients. In addition, the cathelicidin antimicrobial peptide LL-37 was upregulated by the spike protein and significantly elevated in the plasma of patients. Furthermore, LL-37 levels were negatively correlated with thrombin time but positively correlated with fibrinogen level. In addition to platelet activation, cathelicidin peptides enhanced the activity of coagulation factors, such as factor Xa (FXa) and thrombin, which may induce hypercoagulation in diseases with high cathelicidin peptide levels. Injection of cathelicidin peptides promoted the formation of thrombosis, whereas deletion of cathelicidin inhibited thrombosis in vivo. These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors.
Subject(s)
Antimicrobial Cationic Peptides , COVID-19 , Thrombosis , Blood Coagulation Factors , COVID-19/complications , Fibrinogen , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Thrombosis/virology , CathelicidinsSubject(s)
COVID-19/complications , Hematoma/virology , Placenta Diseases/virology , Pregnancy Complications, Infectious/virology , Thrombosis/virology , COVID-19/virology , Female , Hematoma/pathology , Humans , Male , Placenta Diseases/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Retrospective Studies , SARS-CoV-2 , Stillbirth , Thrombosis/pathologyABSTRACT
Clinical, laboratory, and autopsy findings support an association between coronavirus disease-2019 (COVID-19) and thromboembolic disease. Acute COVID-19 infection is characterized by mononuclear cell reactivity and pan-endothelialitis, contributing to a high incidence of thrombosis in large and small blood vessels, both arterial and venous. Observational studies and randomized trials have investigated whether full-dose anticoagulation may improve outcomes compared with prophylactic dose heparin. Although no benefit for therapeutic heparin has been found in patients who are critically ill hospitalized with COVID-19, some studies support a possible role for therapeutic anticoagulation in patients not yet requiring intensive care unit support. We summarize the pathology, rationale, and current evidence for use of anticoagulation in patients with COVID-19 and describe the main design elements of the ongoing FREEDOM COVID-19 Anticoagulation trial, in which 3,600 hospitalized patients with COVID-19 not requiring intensive care unit level of care are being randomized to prophylactic-dose enoxaparin vs therapeutic-dose enoxaparin vs therapeutic-dose apixaban. (FREEDOM COVID-19 Anticoagulation Strategy [FREEDOM COVID]; NCT04512079).
Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Thromboembolism/prevention & control , Thrombosis/prevention & control , COVID-19/therapy , Critical Care , Enoxaparin/therapeutic use , Hospitalization , Humans , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Thromboembolism/virology , Thrombosis/virologyABSTRACT
Emerging clinical evidence suggests that thrombosis in the microvasculature of patients with Coronavirus disease 2019 (COVID-19) plays an essential role in dictating the disease progression. Because of the infectious nature of SARS-CoV-2, patients' fresh blood samples are limited to access for in vitro experimental investigations. Herein, we employ a novel multiscale and multiphysics computational framework to perform predictive modeling of the pathological thrombus formation in the microvasculature using data from patients with COVID-19. This framework seamlessly integrates the key components in the process of blood clotting, including hemodynamics, transport of coagulation factors and coagulation kinetics, blood cell mechanics and adhesive dynamics, and thus allows us to quantify the contributions of many prothrombotic factors reported in the literature, such as stasis, the derangement in blood coagulation factor levels and activities, inflammatory responses of endothelial cells and leukocytes to the microthrombus formation in COVID-19. Our simulation results show that among the coagulation factors considered, antithrombin and factor V play more prominent roles in promoting thrombosis. Our simulations also suggest that recruitment of WBCs to the endothelial cells exacerbates thrombogenesis and contributes to the blockage of the blood flow. Additionally, we show that the recent identification of flowing blood cell clusters could be a result of detachment of WBCs from thrombogenic sites, which may serve as a nidus for new clot formation. These findings point to potential targets that should be further evaluated, and prioritized in the anti-thrombotic treatment of patients with COVID-19. Altogether, our computational framework provides a powerful tool for quantitative understanding of the mechanism of pathological thrombus formation and offers insights into new therapeutic approaches for treating COVID-19 associated thrombosis.
Subject(s)
COVID-19/complications , Microvessels/physiopathology , Thrombosis/physiopathology , Thrombosis/virology , Anticoagulants , Blood Coagulation , Computational Biology , Humans , Models, Biological , SARS-CoV-2ABSTRACT
BACKGROUND: The mortality rate of COVID-19 is elevated in males compared with females. OBJECTIVE: Determine the extent that the elevated thrombotic risk in males relative to females contributes to excess COVID-19 mortality in males. DESIGN: Observational study. SETTING: Data sourced from electronic medical records from over 200 US hospital systems. PARTICIPANTS: 60 877 patients aged 18 years and older hospitalised with COVID-19. EXPOSURE: Exposure variable: biological sex; key variable of interest: thrombosis. PRIMARY OUTCOME MEASURES: Primary outcome was COVID-19 mortality. We measured: (1) mortality rate of males relative to females, (2) rate of thrombotic diagnoses occurring during hospitalisation for COVID-19 in both sexes and (3) mortality rate when evidence of thrombosis was present. RESULTS: The COVID-19 mortality rate of males was 29.9% higher than that of females. Males had a 35.8% higher rate of receiving a thrombotic diagnosis compared with females. The mortality rate of all patients with a thrombotic diagnosis was 40.0%-over twice that of patients with COVID-19 without a thrombotic diagnosis (adjusted OR 2.50 (2.37 to 2.64), p<0.001). When defining thrombosis as either a documented thrombotic diagnosis or a D-dimer level ≥3.0 µg/mL, 16.4% of the excess mortality in male patients could be explained by increased thrombotic risk. CONCLUSIONS: Our findings suggest the higher COVID-19 mortality rate in males may be significantly accounted for by the elevated risk of thrombosis among males. Understanding the mechanisms that underlie increased male thrombotic risk may allow for the advancement of effective anticoagulation strategies that reduce COVID-19 mortality in males.
Subject(s)
COVID-19 , Thrombosis , Adult , Anticoagulants , COVID-19/complications , COVID-19/mortality , Female , Hospital Mortality , Hospitalization , Humans , Male , SARS-CoV-2 , Thrombosis/mortality , Thrombosis/virologyABSTRACT
Post-acute sequelae of COVID (PASC), usually referred to as 'Long COVID' (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, 'brain fog', tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of 'COVID', although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous 'amyloid' form of fibrin that (like other ß-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope. Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored 'triple' anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.
Subject(s)
Amyloid , Anticoagulants/therapeutic use , COVID-19 Drug Treatment , COVID-19 , Lung , SARS-CoV-2/metabolism , Thrombosis , Amyloid/blood , Amyloid/chemistry , COVID-19/blood , Fibrin/chemistry , Fibrin/metabolism , Humans , Lung/metabolism , Lung/virology , Thrombosis/drug therapy , Thrombosis/metabolism , Thrombosis/virologyABSTRACT
Acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection continues to be a worldwide public health crisis. Among the several severe manifestations of this disease, thrombotic processes drive the catastrophic organ failure and mortality in these patients. In addition to a well-established cytokine storm associated with the disease, perturbations in platelets, endothelial cells, and the coagulation system are key in triggering systemic coagulopathy, involving both the macro- and microvasculatures of different organs. Of the several mechanisms that might contribute to dysregulation of these cells following SARS-CoV-2 infection, the current review focuses on the role of activated Janus kinase (JAK) signaling in augmenting thrombotic processes and organ dysfunction. The review concludes with presenting the current understanding and emerging controversies concerning the potential therapeutic applications of JAK inhibitors for ameliorating the inflammation-thrombosis phenotype in COVID-19 patients.
Subject(s)
COVID-19/metabolism , Endothelial Cells/metabolism , Janus Kinases/metabolism , SARS-CoV-2/metabolism , Signal Transduction , Thrombosis/metabolism , Cytokine Release Syndrome/metabolism , Cytokine Release Syndrome/virology , Endothelial Cells/virology , Humans , Thrombosis/virologyABSTRACT
BACKGROUND: The management of the Coronavirus disease 2019 (COVID-19) infected patients continues to be challenging. Critically ill COVID patients are at increased risk of serious thrombotic events and hence increased mortality. On the other side, COVID-19 patients are also showing major life-threatening bleeds, especially when systemic anticoagulation is used. Pro-coagulant propensity in critically ill COVID-19 patients have been published, but very few have described the incidence of major bleeding and its characteristics. METHODS: In this study, we retrospectively observed the incidence of major bleed in 25 critically ill COVID-19 patients admitted to the Intensive Care Unit at the American University of Beirut Medical Center. Six cases were identified and described together with their outcome. RESULTS: Major bleeding occurred in six of the 25 studied patients. Four patients were on therapeutic anticoagulation at the onset of the bleed, two required embolization for bleeding control and one died from hemorrhagic shock. Half of the described cases had unusual sites of bleeding including gluteal and abdominal wall muscles. CONCLUSIONS: A high rate of major bleeding was witnessed in our sample of critically ill patients with COVID-19 infection, with the majority being on therapeutic anticoagulation. This rate may be higher than previously reported, necessitating additional attention from the treating physician when considering empiric therapeutic anticoagulation. Moreover, the uncommon sites of bleeding shed the light on the need for additional studies in our population to identify the predisposing risk factors and mechanisms behind it.
Subject(s)
Anticoagulants , COVID-19 , Hemorrhage , Thrombosis , Anticoagulants/adverse effects , COVID-19/complications , Critical Illness , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Incidence , Retrospective Studies , Thrombosis/prevention & control , Thrombosis/virologySubject(s)
COVID-19 , Hypocalcemia , Thrombosis , Biomarkers/blood , COVID-19/diagnosis , Calcium , Humans , Hypocalcemia/diagnosis , Hypocalcemia/virology , Inflammation , Thrombosis/diagnosis , Thrombosis/virologyABSTRACT
INTRODUCTION: Coronavirus 2 (CoV-2) infection or coronavirus disease 2019 (COVID-19) is frequently associated with microvascular thrombosis.The microthrombosis in COVID-19 is the result of the interplay between inflammation and endotheliopathy. Elevated interleukin-6 (IL-6) characterizes COVID-19 inflammation resulting in endotheliopathy and coagulopathy marked by elevated D-dimer (DD). Aim of this study is to identify and to describe the coagulation changes in 100 moderate COVID-19 patients having lung involvement and to determine the association of coagulopathy with the severity and prognosis. METHODS: Inflammation, endothelial and coagulation molecules were measured in moderate and mild disease. RESULTS: IL-6 and tumor necrosis factor-α (TNF-α) and tissue factor (TF), von Willebrand factor (VWF), and tissue factor pathway inhibitor (TFPI) significantly increased in moderate disease as well as D-dimer, thrombin antithrombin complex (TAT), Fibrinogen (Fib), platelet factor-4 (PF4), ß-thromboglobulin (ß-TG), P-selectin, and platelet adhesion. Shortened clotting time (CT) and clot formation time (CFT), high maximum clot firmness (MCF) and low LY at 30 min were present in 100% of moderate COVID-19 patients compared with mild COVID-19 patients. CONCLUSIONS: These findings demonstrate that moderate COVID-19 has a profound inflammation associated with severee ndotheliopathy and intense coagulation activation uncontrolled by TFPI. Attention should be paid to coagulopathy in COVID-19. Closely monitoring of coagulation and application of appropriate anticoagulation may improve the prognosis of moderate COVID-19 and to prevent the progression to severe COVID-19 disease.
Subject(s)
Blood Coagulation Disorders , COVID-19 , Endothelium, Vascular , Inflammation , Thrombosis , Blood Coagulation Disorders/virology , COVID-19/complications , Endothelium, Vascular/physiopathology , Humans , Inflammation/virology , SARS-CoV-2 , Thrombosis/virologyABSTRACT
Liver injury, characterized predominantly by elevated aspartate aminotransferase and alanine aminotransferase, is a common feature of coronavirus disease 2019 (COVID-19) symptoms caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Additionally, SARS-CoV-2 infection is associated with acute-on-chronic liver failure in patients with cirrhosis and has a notably elevated mortality in patients with alcohol-related liver disease compared to other etiologies. Direct viral infection of the liver with SARS-CoV-2 remains controversial, and alternative pathophysiologic explanations for its hepatic effects are an area of active investigation. In this review, we discuss the effects of SARS-CoV-2 and the inflammatory environment it creates on endothelial cells and platelets more generally and then with a hepatic focus. In doing this, we present vascular inflammation and thrombosis as a potential mechanism of liver injury and liver-related complications in COVID-19.