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1.
Lancet ; 399(10319): 5-7, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1623430
2.
Molecules ; 27(1)2022 Jan 02.
Article in English | MEDLINE | ID: covidwho-1613910

ABSTRACT

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. Anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time, it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of most active compounds was confirmed using lipopolysaccharide (LPS)-treated blood to mimic the conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5-15.2 times as compared to LPS-treated blood.


Subject(s)
Anticoagulants/pharmacology , Azo Compounds/chemistry , Blood Coagulation/drug effects , Hemorrhage/drug therapy , Pyrimidines/chemistry , Animals , Anticoagulants/chemistry , Hemorrhage/chemically induced , Lipopolysaccharides/toxicity , Male , Rabbits , Rats
3.
Int J Mol Sci ; 22(24)2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1580687

ABSTRACT

COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to the identification of a COVID-19-associated coagulopathy, which may contribute to thrombosis, multi-organ damage, and cause of severity and fatality. One significant finding that emerges in prothrombotic abnormalities observed in COVID-19 patients is that the coagulation alterations are mainly mediated by the activation of platelets and intrinsically related to viral-mediated endothelial inflammation. Beyond the well-known role in hemostasis, the ability of platelets to also release various potent cytokines and chemokines has elevated these small cells from simple cell fragments to crucial modulators in the blood, including their inflammatory functions, that have a large influence on the immune response during infectious disease. Indeed, platelets are involved in the pathogenesis of acute lung injury also by promoting NET formation and affecting vascular permeability. Specifically, the deposition by activated platelets of the chemokine platelet factor 4 at sites of inflammation promotes adhesion of neutrophils on endothelial cells and thrombogenesis, and it seems deeply involved in the phenomenon of vaccine-induced thrombocytopenia and thrombosis. Importantly, the hyperactivated platelet phenotype along with evidence of cytokine storm, high levels of P-selectin, D-dimer, and, on the other hand, decreased levels of fibrinogen, von Willebrand factor, and thrombocytopenia may be considered suitable biomarkers that distinguish the late stage of COVID-19 progression in critically ill patients.


Subject(s)
Blood Platelets/physiology , COVID-19/blood , Thrombosis/pathology , Blood Coagulation , Blood Coagulation Disorders/etiology , Blood Platelets/metabolism , Blood Platelets/virology , COVID-19/metabolism , Cytokine Release Syndrome , Endothelial Cells/pathology , Fibrin Fibrinogen Degradation Products , Hemostasis , Humans , Inflammation , Phenotype , Platelet Activation/physiology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Thrombocytopenia/metabolism , Thrombosis/metabolism , Thrombosis/virology
5.
Ann Med ; 53(1): 181-188, 2021 12.
Article in English | MEDLINE | ID: covidwho-1575964

ABSTRACT

OBJECTIVE: To illustrate the effect of corticosteroids and heparin, respectively, on coronavirus disease 2019 (COVID-19) patients' CD8+ T cells and D-dimer. METHODS: In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-dimer, respectively. RESULTS: There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (ß = 0.154%, 95% CI=(0, 0.302), p=.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (ß = 0.163%, 95% CI=(0.027, 0.295), p=.020) significantly increased the rising rate of CD8+ T cell in 14-56 DFS. CONCLUSIONS: The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.


Subject(s)
CD8-Positive T-Lymphocytes/drug effects , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Inflammation/drug therapy , Adult , Aged , Aged, 80 and over , Blood Coagulation/drug effects , Blood Coagulation/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Dose-Response Relationship, Drug , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/immunology , Heparin/administration & dosage , Humans , Inflammation/blood , Inflammation/diagnosis , Inflammation/immunology , Linear Models , Longitudinal Studies , Lymphocyte Count , Male , Methylprednisolone/administration & dosage , Middle Aged , Models, Biological , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Time Factors , Time-to-Treatment , Young Adult
6.
PLoS One ; 16(3): e0247676, 2021.
Article in English | MEDLINE | ID: covidwho-1575816

ABSTRACT

We retrospectively evaluated 2879 hospitalized COVID-19 patients from four hospitals to evaluate the ability of demographic data, medical history, and on-admission laboratory parameters to predict in-hospital mortality. Association of previously published risk factors (age, gender, arterial hypertension, diabetes mellitus, smoking habit, obesity, renal failure, cardiovascular/ pulmonary diseases, serum ferritin, lymphocyte count, APTT, PT, fibrinogen, D-dimer, and platelet count) with death was tested by a multivariate logistic regression, and a predictive model was created, with further validation in an independent sample. A total of 2070 hospitalized COVID-19 patients were finally included in the multivariable analysis. Age 61-70 years (p<0.001; OR: 7.69; 95%CI: 2.93 to 20.14), age 71-80 years (p<0.001; OR: 14.99; 95%CI: 5.88 to 38.22), age >80 years (p<0.001; OR: 36.78; 95%CI: 14.42 to 93.85), male gender (p<0.001; OR: 1.84; 95%CI: 1.31 to 2.58), D-dimer levels >2 ULN (p = 0.003; OR: 1.79; 95%CI: 1.22 to 2.62), and prolonged PT (p<0.001; OR: 2.18; 95%CI: 1.49 to 3.18) were independently associated with increased in-hospital mortality. A predictive model performed with these parameters showed an AUC of 0.81 in the development cohort (n = 1270) [sensitivity of 95.83%, specificity of 41.46%, negative predictive value of 98.01%, and positive predictive value of 24.85%]. These results were then validated in an independent data sample (n = 800). Our predictive model of in-hospital mortality of COVID-19 patients has been developed, calibrated and validated. The model (MRS-COVID) included age, male gender, and on-admission coagulopathy markers as positively correlated factors with fatal outcome.


Subject(s)
COVID-19/mortality , Aged , Aged, 80 and over , Blood Coagulation , COVID-19/blood , COVID-19/diagnosis , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification
7.
Front Immunol ; 12: 778913, 2021.
Article in English | MEDLINE | ID: covidwho-1574246

ABSTRACT

The current global pandemic of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) causing COVID-19, has infected millions of people and continues to pose a threat to many more. Angiotensin-Converting Enzyme 2 (ACE2) is an important player of the Renin-Angiotensin System (RAS) expressed on the surface of the lung, heart, kidney, neurons, and endothelial cells, which mediates SARS-CoV-2 entry into the host cells. The cytokine storms of COVID-19 arise from the large recruitment of immune cells because of the dis-synchronized hyperactive immune system, lead to many abnormalities including hyper-inflammation, endotheliopathy, and hypercoagulability that produce multi-organ dysfunction and increased the risk of arterial and venous thrombosis resulting in more severe illness and mortality. We discuss the aberrated interconnectedness and forthcoming crosstalks between immunity, the endothelium, and coagulation, as well as how sex disparities affect the severity and outcome of COVID-19 and harm men especially. Further, our conceptual framework may help to explain why persistent symptoms, such as reduced physical fitness and fatigue during long COVID, may be rooted in the clotting system.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2 , Biomarkers , Blood Coagulation , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , COVID-19/complications , COVID-19/diagnosis , Cytokines/metabolism , Disease Susceptibility , Endothelium/metabolism , Female , Host-Pathogen Interactions/immunology , Humans , Inflammation Mediators , Male , Renin-Angiotensin System , Severity of Illness Index , Sex Factors
8.
Biol Chem ; 402(12): 1505-1518, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1562377

ABSTRACT

COVID-19 primarily affects the respiratory system and may lead to severe systemic complications, such as acute respiratory distress syndrome (ARDS), multiple organ failure, cytokine storm, and thromboembolic events. Depending on the immune status of the affected individual early disease control can be reached by a robust type-I-interferon (type-I-IFN) response restricting viral replication. If type-I-IFN upregulation is impaired, patients develop severe COVID-19 that involves profound alveolitis, endothelitis, complement activation, recruitment of immune cells, as well as immunothrombosis. In patients with proper initial disease control there can be a second flare of type-I-IFN release leading to post-COVID manifestation such as chilblain-like lesions that are characterized by thrombosis of small vessels in addition to an inflammatory infiltrate resembling lupus erythematosus (LE). Mechanistically, SARS-CoV-2 invades pneumocytes and endothelial cells by acting on angiotensin-II-converting enzyme 2 (ACE2). It is hypothesized, that viral uptake might downregulate ACE2 bioavailability and enhance angiotensin-II-derived pro-inflammatory and pro-thrombotic state. Since ACE2 is encoded on the X chromosome these conditions might also be influenced by gender-specific regulation. Taken together, SARS-CoV-2 infection affects the vascular compartment leading to variable thrombogenic or inflammatory response depending on the individual immune response status.


Subject(s)
Blood Coagulation , COVID-19 , Humans
9.
Biomed Res Int ; 2021: 7073348, 2021.
Article in English | MEDLINE | ID: covidwho-1560583

ABSTRACT

Coronavirus disease 2019 (COVID-19) may lead to acute respiratory disease; cardiovascular, gastrointestinal, and coagulation complications; and even death. One of the major complications is cardiovascular disorders, including arrhythmias, myocarditis, pericarditis, and acute coronary artery disease. The aim of this study was to evaluate the frequency of cardiovascular complications and to determine its association with the prognosis of COVID-19 patients. In a prospective analytic study, 137 hospitalized COVID-19 patients were enrolled. During hospitalization, an electrocardiogram (ECG) was performed every other day, and laboratory tests such as cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were done 0, 6, and 12 hours after admission. These tests were repeated for patients with chest pain or ECG changes. Patients were categorized into three groups (improved, complicated, and expired patients) and assessed for the rate and type of arrhythmias, cardiac complications, lab tests, and outcomes of treatments. There was no significant relationship among the three groups related to primary arrhythmia and arrhythmias during treatment. The most common arrhythmia during hospitalization and after treatment was ST-T fragment changes. There was a significant age difference between the three groups (P = 0.001). There was a significant difference among the three groups for some underlying diseases, including diabetes mellitus (P = 0.003) and hyperlipidemia (P = 0.004). In our study, different types of arrhythmias had no association with patients' outcomes but age over 60 years, diabetes mellitus, and hyperlipidemia played an important role in the prognosis of COVID-19 cases.


Subject(s)
COVID-19/complications , COVID-19/pathology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/pathology , Adult , Aged , Blood Coagulation/physiology , COVID-19/metabolism , Cardiovascular Diseases/metabolism , Creatine Kinase/metabolism , Electrocardiography/methods , Female , Heart/physiopathology , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Troponin I/metabolism , Young Adult
11.
Open Heart ; 8(2)2021 11.
Article in English | MEDLINE | ID: covidwho-1523054

ABSTRACT

BACKGROUND: Early in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately coprescribed two anticoagulants following a medication change and associated monitoring. OBJECTIVE: To describe which people were switched from warfarin to DOACs; identify potentially unsafe coprescribing of anticoagulants; and assess whether abnormal clotting results have become more frequent during the pandemic. METHODS: With the approval of NHS England, we conducted a cohort study using routine clinical data from 24 million NHS patients in England. RESULTS: 20 000 of 164 000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in coprescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. International normalised ratio (INR) testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420). CONCLUSIONS: Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people coprescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.


Subject(s)
Anticoagulants/administration & dosage , Blood Coagulation/drug effects , COVID-19 , Drug Substitution/standards , Factor Xa Inhibitors/administration & dosage , Practice Guidelines as Topic/standards , Practice Patterns, Physicians'/standards , State Medicine/standards , Warfarin/administration & dosage , Aged , Anticoagulants/adverse effects , Blood Coagulation Tests , Drug Monitoring , Drug Prescriptions , Drug Substitution/adverse effects , Drug Utilization/standards , England , Factor Xa Inhibitors/adverse effects , Female , Humans , Male , Middle Aged , Patient Safety , Primary Health Care/standards , Retrospective Studies , Risk Assessment , Risk Factors , Warfarin/adverse effects
13.
Int J Mol Sci ; 22(21)2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1512382

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with a great impact on social and economic activities, as well as public health. In most patients, the symptoms of COVID-19 are a high-grade fever and a dry cough, and spontaneously resolve within ten days. However, in severe cases, COVID-19 leads to atypical bilateral interstitial pneumonia, acute respiratory distress syndrome, and systemic thromboembolism, resulting in multiple organ failure with high mortality and morbidity. SARS-CoV-2 has immune evasion mechanisms, including inhibition of interferon signaling and suppression of T cell and B cell responses. SARS-CoV-2 infection directly and indirectly causes dysregulated immune responses, platelet hyperactivation, and endothelial dysfunction, which interact with each other and are exacerbated by cardiovascular risk factors. In this review, we summarize current knowledge on the pathogenic basis of thromboinflammation and endothelial injury in COVID-19. We highlight the distinct contributions of dysregulated immune responses, platelet hyperactivation, and endothelial dysfunction to the pathogenesis of COVID-19. In addition, we discuss potential therapeutic strategies targeting these mechanisms.


Subject(s)
COVID-19/pathology , Endothelium, Vascular/physiopathology , Thrombosis/etiology , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Blood Coagulation , COVID-19/complications , COVID-19/drug therapy , COVID-19/virology , Endothelium, Vascular/metabolism , Humans , Immunity, Innate , Platelet Activation , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology
14.
J Vasc Surg Venous Lymphat Disord ; 9(3): 605-614.e2, 2021 05.
Article in English | MEDLINE | ID: covidwho-1510080

ABSTRACT

OBJECTIVE: Early reports suggest that patients with novel coronavirus disease-2019 (COVID-19) infection carry a significant risk of altered coagulation with an increased risk for venous thromboembolic events. This report investigates the relationship of significant COVID-19 infection and deep venous thrombosis (DVT) as reflected in the patient clinical and laboratory characteristics. METHODS: We reviewed the demographics, clinical presentation, laboratory and radiologic evaluations, results of venous duplex imaging and mortality of COVID-19-positive patients (18-89 years) admitted to the Indiana University Academic Health Center. Using oxygen saturation, radiologic findings, and need for advanced respiratory therapies, patients were classified into mild, moderate, or severe categories of COVID-19 infection. A descriptive analysis was performed using univariate and bivariate Fisher's exact and Wilcoxon rank-sum tests to examine the distribution of patient characteristics and compare the DVT outcomes. A multivariable logistic regression model was used to estimate the adjusted odds ratio of experiencing DVT and a receiver operating curve analysis to identify the optimal cutoff for d-dimer to predict DVT in this COVID-19 cohort. Time to the diagnosis of DVT from admission was analyzed using log-rank test and Kaplan-Meier plots. RESULTS: Our study included 71 unique COVID-19-positive patients (mean age, 61 years) categorized as having 3% mild, 14% moderate, and 83% severe infection and evaluated with 107 venous duplex studies. DVT was identified in 47.8% of patients (37% of examinations) at an average of 5.9 days after admission. Patients with DVT were predominantly male (67%; P = .032) with proximal venous involvement (29% upper and 39% in the lower extremities with 55% of the latter demonstrating bilateral involvement). Patients with DVT had a significantly higher mean d-dimer of 5447 ± 7032 ng/mL (P = .0101), and alkaline phosphatase of 110 IU/L (P = .0095) than those without DVT. On multivariable analysis, elevated d-dimer (P = .038) and alkaline phosphatase (P = .021) were associated with risk for DVT, whereas age, sex, elevated C-reactive protein, and ferritin levels were not. A receiver operating curve analysis suggests an optimal d-dimer value of 2450 ng/mL cutoff with 70% sensitivity, 59.5% specificity, and 61% positive predictive value, and 68.8% negative predictive value. CONCLUSIONS: This study suggests that males with severe COVID-19 infection requiring hospitalization are at highest risk for developing DVT. Elevated d-dimers and alkaline phosphatase along with our multivariable model can alert the clinician to the increased risk of DVT requiring early evaluation and aggressive treatment.


Subject(s)
Alkaline Phosphatase/blood , COVID-19 , Extremities , Fibrin Fibrinogen Degradation Products/analysis , Risk Assessment/methods , Ultrasonography, Doppler, Duplex , Venous Thrombosis , Anticoagulants/administration & dosage , Biomarkers/blood , Blood Coagulation , COVID-19/blood , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Early Diagnosis , Extremities/blood supply , Extremities/diagnostic imaging , Female , Humans , Indiana/epidemiology , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , SARS-CoV-2/isolation & purification , Time-to-Treatment/statistics & numerical data , Ultrasonography, Doppler, Duplex/methods , Ultrasonography, Doppler, Duplex/statistics & numerical data , Venous Thrombosis/diagnosis , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
16.
Indian J Pathol Microbiol ; 64(4): 735-740, 2021.
Article in English | MEDLINE | ID: covidwho-1485280

ABSTRACT

Background: COVID-19 is a pandemic viral disease that has affected the Indian population very badly with more than 8.46 million cases and > 0.125 million deaths. Aim: Primary objective of the study is to establish the role of hematological, coagulation and inflammatory biomarkers in early identification of clinically severe covid-19 cases. Materials and Methods: This study was conducted from July 2020 to August 2020 at a dedicated COVID-19 referral hospital in central India. Only RT-PCR confirmed COVID-19 positive 300 cases admitted in the hospital were included in this study. Based on the clinical assessment, patients were categorised as mild, moderate, and severe groups as per ICMR guidelines. Blood samples of all cases were tested for haematological, coagulation and inflammatory biomarkers and mean values were compared among the three groups of patients. Results: 46% patients belonged to >60 years of age group. Hematological parameters like total leukocyte count, absolute neutrophil count, Neutrophil: Lymphocyte ratio, Platelet: Lymphocyte ratio significantly increased with lymphocytopenia (P=0.001). Coagulation profile(D-dimer and PT) and inflammatory biomarkers like CRP, LDH, ferritin, procalcitonin and NT- Pro BNP, all were significantly increased with severity of patients(p=0.001). ROC plotted for all the parameters between severe v/s non-severe cases showed that CRP, LDH and D-dimer had a good discriminative precision with AUC >0.8. Conclusion: We suggest that biochemical markers like CRP, LDH and D-dimer can be used as a screening tool to differentiate severe patients from non-severe patients of Covid-19 disease in order to identify severe disease at early stage for optimal utilization of resources & reducing further morbidity & mortality.


Subject(s)
Biomarkers/blood , Blood Coagulation/physiology , COVID-19/physiopathology , Early Diagnosis , Inflammation/blood , Inflammation/physiopathology , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Female , Humans , India , Male , Middle Aged , Predictive Value of Tests , Prognosis , SARS-CoV-2
17.
Clin Appl Thromb Hemost ; 27: 10760296211042940, 2021.
Article in English | MEDLINE | ID: covidwho-1484251

ABSTRACT

The world is in a hard battle against COVID-19. Endothelial cells are among the most critical targets of SARS-CoV-2. Dysfunction of endothelium leads to vascular injury following by coagulopathies and thrombotic conditions in the vital organs increasing the risk of life-threatening events. Growing evidences revealed that endothelial dysfunction and consequent thrombotic conditions are associated with the severity of outcomes. It is not yet fully clear that these devastating sequels originate directly from the virus or a side effect of virus-induced cytokine storm. Due to endothelial dysfunction, plasma levels of some biomarkers are changed and relevant clinical manifestations appear as well. Stabilization of endothelial integrity and supporting its function are among the promising therapeutic strategies. Other than respiratory, COVID-19 could be called a systemic vascular disease and this aspect should be scrutinized in more detail in order to reduce related mortality. In the present investigation, the effects of COVID-19 on endothelial function and thrombosis formation are discussed. In this regard, critical players, laboratory findings, clinical manifestation, and suggestive therapies are presented.


Subject(s)
Blood Coagulation , COVID-19/virology , Endothelial Cells/virology , Endothelium, Vascular/virology , SARS-CoV-2/pathogenicity , Thrombosis/virology , Animals , COVID-19/blood , COVID-19/pathology , COVID-19/physiopathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Host-Pathogen Interactions , Humans , Signal Transduction , Thrombosis/blood , Thrombosis/pathology , Thrombosis/physiopathology
18.
Blood Coagul Fibrinolysis ; 32(7): 458-467, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1470186

ABSTRACT

Early descriptions of COVID-19 associated coagulopathy identified it as a disseminated intravascular coagulation (DIC). However, recent studies have highlighted the potential role of endothelial cell injury in its pathogenesis, and other possible underlying mechanisms are being explored. This study aimed to analyse the coagulation parameters of critically and noncritically ill patients with COVID-19 bilateral pneumonia, determine if coagulation factors consumption occurs and explore other potential mechanisms of COVID-19 coagulopathy. Critically and noncritically ill patients with a diagnosis of COVID-19 bilateral pneumonia were recruited. For each patient, we performed basic coagulation tests, quantification of coagulation factors and physiological inhibitor proteins, an evaluation of the fibrinolytic system and determination of von Willebrand Factor (vWF) and ADAMTS13. Laboratory data were compared with clinical data and outcomes. The study involved 62 patients (31 ICU, 31 non-ICU). The coagulation parameters assessment demonstrated normal median prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) in our cohort and all coagulation factors were within normal range. PAI-1 median levels were elevated (median 52.6 ng/ml; IQR 37.2-85.7), as well as vWF activity (median 216%; IQR 196-439) and antigen (median 174%; IQR 153.5-174.1). A mild reduction of ADAMTS13 was observed in critically ill patients and nonsurvivors. We demonstrated an inverse correlation between ADAMTS13 levels and inflammatory markers, D-dimer and SOFA score in our cohort. Elevated vWF and PAI-1 levels, and a mild reduction of ADAMTS13 in the most severe patients, suggest that COVID-19 coagulopathy is an endotheliopathy that has shared features with thrombotic microangiopathy.


Subject(s)
ADAMTS13 Protein/deficiency , Blood Coagulation , COVID-19/blood , ADAMTS13 Protein/blood , Adult , Aged , COVID-19/complications , Critical Illness/epidemiology , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index
20.
Int J Biol Macromol ; 192: 1040-1057, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1466382

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent responsible for the Coronavirus Disease-2019 (COVID-19) pandemic, has infected over 185 million individuals across 200 countries since December 2019 resulting in 4.0 million deaths. While COVID-19 is primarily associated with respiratory illnesses, an increasing number of clinical reports indicate that severely ill patients often develop thrombotic complications that are associated with increased mortality. As a consequence, treatment strategies that target COVID-associated thrombosis are of utmost clinical importance. An array of pharmacologically active compounds from natural products exhibit effects on blood coagulation pathways, and have generated interest for their potential therapeutic applications towards thrombotic diseases. In particular, a number of snake venom compounds exhibit high specificity on different blood coagulation factors and represent excellent tools that could be utilized to treat thrombosis. The aim of this review is to provide a brief summary of the current understanding of COVID-19 associated thrombosis, and highlight several snake venom compounds that could be utilized as antithrombotic agents to target this disease.


Subject(s)
COVID-19/blood , Fibrinolytic Agents/pharmacology , Snake Venoms/pharmacology , Thrombosis/drug therapy , Thrombosis/virology , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/pathology , Humans , Pandemics , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
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