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1.
Thromb Res ; 220: 100-106, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2150681

ABSTRACT

INTRODUCTION: COVID-19 disease, which has recently become an important cause of mortality and morbidity all over the world, is remarkably associated with thrombotic complications. Although many factors are responsible for these increased thrombotic complications in COVID-19 disease, its relationship with a marker that increases the risk of thrombosis such as Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) has not yet been clarified. This is the first study to examine the potential diagnostic and prognostic value of SCUBE1 levels in patients with COVID-19. In this study, we aimed to clarify the relationship between the increased risk of thrombosis and SCUBE1 in the course of COVID-19 disease. MATERIALS AND METHODS: 553 patients with COVID-19 and 553 healthy controls were compared in terms of SCUBE1 levels. Additionally, patients with COVID-19 were divided into two groups according to their SCUBE1 levels and compared in terms of severity of disease, thrombotic complications and in-hospital mortality. RESULTS: SCUBE1 levels were significantly higher in patients with COVID-19 compared to the control group (p < 0.001). Plasma SCUBE1 levels were significantly higher in patients with severe disease and thrombotic complications, those with mild to moderate disease, and those without thrombotic complications (p < 0.001, for both). In addition, SCUBE1 was found to be an independent predictor of in-hospital mortality (p < 0.001). CONCLUSIONS: SCUBE1 may be one of the major determinants of thrombotic complications, which is an increased cause of mortality and morbidity in COVID-19 patients so inhibition of this peptide may be among the therapeutic targets in patients with COVID-19.


Subject(s)
COVID-19 , Thrombosis , Humans , Hospital Mortality , COVID-19/complications , Thrombosis/etiology , Plasma , Severity of Illness Index , Calcium-Binding Proteins
2.
Clin Hemorheol Microcirc ; 82(2): 149-155, 2022.
Article in English | MEDLINE | ID: covidwho-2141600

ABSTRACT

BACKGROUND: Elevated estimated blood viscosity (EBV), derived from hematocrit and globulins, is associated with thrombotic complications, organ failure, and higher mortality in COVID-19 patients. Although informative, EBV does not account for cellular interactions or fibrinogen. OBJECTIVE: Investigate whether patients with acute and recent COVID-19 have altered whole blood viscosity (WBV) when measured at both high and low shear rates using in vitro blood samples from patients. METHODS: Cross-sectional study of 58 patients: 15 in the intensive care unit with acute COVID-19, 32 convalescent (9 < 8weeks [W] from acute infection, 23 > 8 W), and 11 controls without COVID-19. WBV was measured at high (300 s-1) and low (5 s-1) shear rates (HSR, LSR) using a scanning capillary viscometer.RESULTSAcute and convalescent patients < 8 W had mean WBV at LSR (16.0 centipoise [cP] and 15.1 cP) and HSR (5.1 cP and 4.7 cP). Mean WBV of convalescent > 8 W and control patients were 12.3 cP and 13.0 cP at LSR, and 4.1 cP and 4.2 cP at HSR. Acute and < 8 W patients had significantly higher WBV at both HSR and LSR compared to patients > 8 W (all p≤0.01). No significant differences in WBV were observed between acute and < 8 W patients, or between patients > 8 W and controls. CONCLUSIONS: Hyperviscosity provides a possible explanation for thrombotic risk in acute and convalescent (< 8 W) patients. These findings have important implications for thromboprophylaxis.


Subject(s)
COVID-19 , Thrombophilia , Thrombosis , Venous Thromboembolism , Humans , Cross-Sectional Studies , Anticoagulants , Venous Thromboembolism/complications , Blood Viscosity , Thrombosis/etiology
3.
Nat Commun ; 13(1): 7169, 2022 Nov 23.
Article in English | MEDLINE | ID: covidwho-2133431

ABSTRACT

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Here we compare rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 with the background (expected) rates in the general population. In addition, we compare the rates of the same adverse events among persons infected with SARS-CoV-2 with background rates. Primary care and linked hospital data from Catalonia, Spain informed the study, with participants vaccinated with BNT162b2 or ChAdOx1 (27/12/2020-23/06/2021), COVID-19 cases (01/09/2020-23/06/2021) or present in the database as of 01/01/2017. We included 2,021,366 BNT162b2 (1,327,031 with 2 doses), 592,408 ChAdOx1, 174,556 COVID-19 cases, and 4,573,494 background participants. Standardised incidence ratios for venous thromboembolism were 1.18 (95% CI 1.06-1.32) and 0.92 (0.81-1.05) after first- and second dose BNT162b2, and 0.92 (0.71-1.18) after first dose ChAdOx1. The standardised incidence ratio for venous thromboembolism in COVID-19 was 10.19 (9.43-11.02). Standardised incidence ratios for arterial thromboembolism were 1.02 (0.95-1.09) and 1.04 (0.97-1.12) after first- and second dose BNT162b2, 1.06 (0.91-1.23) after first-dose ChAdOx1 and 4.13 (3.83-4.45) for COVID-19. Standardised incidence ratios for thrombocytopenia were 1.49 (1.43-1.54) and 1.40 (1.35-1.45) after first- and second dose BNT162b2, 1.28 (1.19-1.38) after first-dose ChAdOx1 and 4.59 (4.41- 4.77) for COVID-19. While rates of thrombosis with thrombocytopenia were generally similar to background rates, the standardised incidence ratio for pulmonary embolism with thrombocytopenia after first-dose BNT162b2 was 1.70 (1.11-2.61). These findings suggest that the safety profiles of BNT162b2 and ChAdOx1 are similar, with rates of adverse events seen after vaccination typically similar to background rates. Meanwhile, rates of adverse events are much increased for COVID-19 cases further underlining the importance of vaccination.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Venous Thromboembolism , Humans , SARS-CoV-2 , Spain/epidemiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , BNT162 Vaccine , Thrombocytopenia/epidemiology , Thrombocytopenia/etiology , Thrombosis/epidemiology , Thrombosis/etiology , Vaccination/adverse effects
4.
Nat Commun ; 13(1): 7167, 2022 Nov 23.
Article in English | MEDLINE | ID: covidwho-2133430

ABSTRACT

Population-based studies can provide important evidence on the safety of COVID-19 vaccines. Using data from the United Kingdom, here we compare observed rates of thrombosis and thrombocytopenia following vaccination against SARS-CoV-2 and infection with SARS-CoV-2 with background (expected) rates in the general population. First and second dose cohorts for ChAdOx1 or BNT162b2 between 8 December 2020 and 2 May 2021 in the United Kingdom were identified. A further cohort consisted of people with no prior COVID-19 vaccination who were infected with SARS-Cov-2 identified by a first positive PCR test between 1 September 2020 and 2 May 2021. The fourth general population cohort for background rates included those people in the database as of 1 January 2017. In total, we included 3,768,517 ChAdOx1 and 1,832,841 BNT162b2 vaccinees, 401,691 people infected with SARS-CoV-2, and 9,414,403 people from the general population. An increased risk of venous thromboembolism was seen after first dose of ChAdOx1 (standardized incidence ratio: 1.12 [95% CI: 1.05 to 1.20]), BNT162b2 (1.12 [1.03 to 1.21]), and positive PCR test (7.27 [6.86 to 7.72]). Rates of cerebral venous sinus thrombosis were higher than otherwise expected after first dose of ChAdOx1 (4.14 [2.54 to 6.76]) and a SARS-CoV-2 PCR positive test (3.74 [1.56 to 8.98]). Rates of arterial thromboembolism after vaccination were no higher than expected but were increased after a SARS-CoV-2 PCR positive test (1.39 [1.21 to 1.61]). Rates of venous thromboembolism with thrombocytopenia were higher than expected after a SARS-CoV-2 PCR positive test (5.76 [3.19 to 10.40]).


Subject(s)
COVID-19 Vaccines , COVID-19 , Thrombocytopenia , Thrombosis , Venous Thromboembolism , Humans , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , SARS-CoV-2 , Thrombocytopenia/epidemiology , Thrombocytopenia/etiology , Thrombosis/epidemiology , Thrombosis/etiology , Vaccination/adverse effects , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , United Kingdom
5.
Eur J Vasc Endovasc Surg ; 64(2-3): 150-152, 2022.
Article in English | MEDLINE | ID: covidwho-2130715
6.
Int J Mol Sci ; 23(22)2022 Nov 17.
Article in English | MEDLINE | ID: covidwho-2116210

ABSTRACT

Coronavirus disease-19 (COVID-19) patients are prone to thrombotic complications that may increase morbidity and mortality. These complications are thought to be driven by endothelial activation and tissue damage promoted by the systemic hyperinflammation associated with COVID-19. However, the exact mechanisms contributing to these complications are still unknown. To identify additional mechanisms contributing to the aberrant clotting observed in COVID-19 patients, we analyzed platelets from COVID-19 patients compared to those from controls using mass spectrometry. We identified increased serum amyloid A (SAA) levels, an acute-phase protein, on COVID-19 patients' platelets. In addition, using an in vitro adhesion assay, we showed that healthy platelets adhered more strongly to wells coated with COVID-19 patient serum than to wells coated with control serum. Furthermore, inhibitors of integrin aIIbß3 receptors, a mediator of platelet-SAA binding, reduced platelet adhesion to recombinant SAA and to wells coated with COVID-19 patient serum. Our results suggest that SAA may contribute to the increased platelet adhesion observed in serum from COVID-19 patients. Thus, reducing SAA levels by decreasing inflammation or inhibiting SAA platelet-binding activity might be a valid approach to abrogate COVID-19-associated thrombotic complications.


Subject(s)
COVID-19 , Thrombosis , Humans , Serum Amyloid A Protein/metabolism , COVID-19/complications , Platelet Adhesiveness , Blood Platelets/metabolism , Thrombosis/etiology , Thrombosis/metabolism , Integrins/metabolism , Tissue Adhesions
7.
J Ayub Med Coll Abbottabad ; 34(3): 557-562, 2022.
Article in English | MEDLINE | ID: covidwho-2115707

ABSTRACT

BACKGROUND: Coronavirus disease 19 (COVID-19) is a viral disease caused by SARS-CoV-2. There is an increased incidence of a thromboembolic phenomenon in patients with COVID-19 infection. Pulmonary embolism is the most common thrombotic presentation in COVID-19 patients. Extra-pulmonary thrombosis is an unusual thrombotic complication of COVID-19 disease. METHODS: This study was conducted at The Aga Khan University Hospital from June-July'2021. Patients clinical and laboratory findings, treatment, and outcomes were recorded. RESULTS: We report three cases with the diagnosis of COVID-19 pneumonia associated with extra-pulmonary thrombosis from June to July 2021. The mean age of the patients were 66.3 and two of them (66.6%) were male. The diagnosis of COVID-19 was confirmed by real-time reverse transcriptase-polymerase chain reaction analysis in all the three patients. Extra-pulmonary thrombosis was identified in the celiac artery and splenic veins in case 1, left common iliac artery in case 2, and left ventricular apical thrombus in case 3. All the patients were treated with anticoagulation. In total, two patients were discharged home after total recovery, while the third patient died. CONCLUSIONS: The take-home message is that COVID-19 infection is a pro-thrombotic condition that can provoke arterial and venous thrombosis. Extra-pulmonary thrombosis is increasingly identified with COVID-19 infection. It is important to remember that the patient might have no potential risk factor for thromboses, as COVID-19 infection per se is a risk to induce thrombosis.


Subject(s)
COVID-19 , Thrombosis , Venous Thrombosis , Humans , Male , Female , COVID-19/complications , SARS-CoV-2 , Anticoagulants/therapeutic use , Venous Thrombosis/etiology , Thrombosis/etiology
8.
Front Immunol ; 13: 933960, 2022.
Article in English | MEDLINE | ID: covidwho-2119695

ABSTRACT

Background: PTX3 is an important mediator of inflammation and innate immunity. We aimed at assessing its prognostic value in a large cohort of patients hospitalized with COVID-19. Methods: Levels of PTX3 were measured in 152 patients hospitalized with COVID-19 at San Gerardo Hospital (Monza, Italy) since March 2020. Cox regression was used to identify predictors of time from admission to in-hospital death or mechanical ventilation. Crude incidences of death were compared between patients with PTX3 levels higher or lower than the best cut-off estimated with the Maximally Selected Rank Statistics Method. Results: Upon admission, 22% of the patients required no oxygen, 46% low-flow oxygen, 30% high-flow nasal cannula or CPAP-helmet and 3% MV. Median level of PTX3 was 21.7 (IQR: 13.5-58.23) ng/ml. In-hospital mortality was 25% (38 deaths); 13 patients (8.6%) underwent MV. PTX3 was associated with risk of death (per 10 ng/ml, HR 1.08; 95%CI 1.04-1.11; P<0.001) and death/MV (HR 1.04; 95%CI 1.01-1.07; P=0.011), independently of other predictors of in-hospital mortality, including age, Charlson Comorbidity Index, D-dimer and C-reactive protein (CRP). Patients with PTX3 levels above the optimal cut-off of 39.32 ng/ml had significantly higher mortality than the others (55% vs 8%, P<0.001). Higher PTX3 plasma levels were found in 14 patients with subsequent thrombotic complications (median [IQR]: 51.4 [24.6-94.4] versus 21 [13.4-55.2]; P=0.049). Conclusions: High PTX3 levels in patients hospitalized with COVID-19 are associated with a worse outcome. The evaluation of this marker could be useful in prognostic stratification and identification of patients who could benefit from immunomodulant therapy.


Subject(s)
COVID-19 , Thrombosis , Humans , Hospital Mortality , Serum Amyloid P-Component/metabolism , Thrombosis/etiology , Intubation, Intratracheal
9.
Thromb Res ; 220: 35-47, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2106047

ABSTRACT

Evidence of micro- and macro-thrombi in the arteries and veins of critically ill COVID-19 patients and in autopsies highlight the occurrence of COVID-19-associated coagulopathy (CAC). Clinical findings of critically ill COVID-19 patients point to various mechanisms for CAC; however, the definitive underlying cause is unclear. Multiple factors may contribute to the prothrombotic state in patients with COVID-19. Aberrant expression of tissue factor (TF), an initiator of the extrinsic coagulation pathway, leads to thrombotic complications during injury, inflammation, and infections. Clinical evidence suggests that TF-dependent coagulation activation likely plays a role in CAC. Multiple factors could trigger abnormal TF expression and coagulation activation in patients with severe COVID-19 infection. Proinflammatory cytokines that are highly elevated in COVID-19 (IL-1ß, IL-6 and TNF-α) are known induce TF expression on leukocytes (e.g. monocytes, macrophages) and non-immune cells (e.g. endothelium, epithelium) in other conditions. Antiphospholipid antibodies, TF-positive extracellular vesicles, pattern recognition receptor (PRR) pathways and complement activation are all candidate factors that could trigger TF-dependent procoagulant activity. In addition, coagulation factors, such as thrombin, may further potentiate the induction of TF via protease-activated receptors on cells. In this systematic review, with other viral infections, we discuss potential mechanisms and cell-type-specific expressions of TF during SARS-CoV-2 infection and its role in the development of CAC.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombosis , Humans , Thromboplastin/metabolism , COVID-19/complications , Critical Illness , SARS-CoV-2 , Blood Coagulation Disorders/complications , Thrombosis/etiology
10.
Turk Kardiyol Dern Ars ; 50(3): 228-230, 2022 04.
Article in English | MEDLINE | ID: covidwho-2090747

ABSTRACT

A 63-year-old man with active COVID-19 infection and a history of coronary artery bypass grafting presented with acute thrombotic occlusion of saphenous venous graft which was anastomosed to the left anterior descending artery. Initial antegrade approach, complicated by a small leakage in the distal left anterior descending artery, was later converted to a retrograde approach via occluded saphenous vein graft. After successful stenting, TIMI 3 flow was achieved.


Subject(s)
COVID-19 , Thrombosis , COVID-19/complications , Coronary Angiography/adverse effects , Coronary Artery Bypass/adverse effects , Coronary Vessels/surgery , Humans , Male , Middle Aged , Saphenous Vein , Thrombosis/diagnostic imaging , Thrombosis/etiology
11.
J Med Internet Res ; 24(10): e35860, 2022 10 21.
Article in English | MEDLINE | ID: covidwho-2089625

ABSTRACT

BACKGROUND: COVID-19 has been observed to be associated with venous and arterial thrombosis. The inflammatory disease prolongs hospitalization, and preexisting comorbidities can intensity the thrombotic burden in patients with COVID-19. However, venous thromboembolism, arterial thrombosis, and other vascular complications may go unnoticed in critical care settings. Early risk stratification is paramount in the COVID-19 patient population for proactive monitoring of thrombotic complications. OBJECTIVE: The aim of this exploratory research was to characterize thrombotic complication risk factors associated with COVID-19 using information from electronic health record (EHR) and insurance claims databases. The goal is to develop an approach for analysis using real-world data evidence that can be generalized to characterize thrombotic complications and additional conditions in other clinical settings as well, such as pneumonia or acute respiratory distress syndrome in COVID-19 patients or in the intensive care unit. METHODS: We extracted deidentified patient data from the insurance claims database IBM MarketScan, and formulated hypotheses on thrombotic complications in patients with COVID-19 with respect to patient demographic and clinical factors using logistic regression. The hypotheses were then verified with analysis of deidentified patient data from the Research Patient Data Registry (RPDR) Mass General Brigham (MGB) patient EHR database. Data were analyzed according to odds ratios, 95% CIs, and P values. RESULTS: The analysis identified significant predictors (P<.001) for thrombotic complications in 184,831 COVID-19 patients out of the millions of records from IBM MarketScan and the MGB RPDR. With respect to age groups, patients 60 years and older had higher odds (4.866 in MarketScan and 6.357 in RPDR) to have thrombotic complications than those under 60 years old. In terms of gender, men were more likely (odds ratio of 1.245 in MarketScan and 1.693 in RPDR) to have thrombotic complications than women. Among the preexisting comorbidities, patients with heart disease, cerebrovascular diseases, hypertension, and personal history of thrombosis all had significantly higher odds of developing a thrombotic complication. Cancer and obesity were also associated with odds>1. The results from RPDR validated the IBM MarketScan findings, as they were largely consistent and afford mutual enrichment. CONCLUSIONS: The analysis approach adopted in this study can work across heterogeneous databases from diverse organizations and thus facilitates collaboration. Searching through millions of patient records, the analysis helped to identify factors influencing a phenotype. Use of thrombotic complications in COVID-19 patients represents only a case study; however, the same design can be used across other disease areas by extracting corresponding disease-specific patient data from available databases.


Subject(s)
COVID-19 , Thrombosis , Humans , Female , COVID-19/complications , COVID-19/epidemiology , Thrombosis/epidemiology , Thrombosis/etiology , Risk Factors , Retrospective Studies , Odds Ratio
12.
Medicine (Baltimore) ; 101(42): e31188, 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2087898

ABSTRACT

OBJECTIVES: Acute gastrointestinal injury (AGI) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a low incidence of complications in patients admitted to the intensive care unit (ICU). Pathophysiological knowledge related to AGI is limited, as few studies have been published on this topic. Therefore, this study was carried out to identify the clinical and histopathological features of patients with SARS-CoV-2 infection and grade IV AGI. METHODS: This is a retrospective case study of fifteen patients with SARS-CoV-2 infection and grade IV AGI who underwent emergency surgery. RESULTS: This study revealed a mortality rate of 62.5%. The most frequent gastrointestinal symptoms were abdominal distension (100%) and increased gastric residual volume (93.3%). Distended bowel loops on plain abdominal radiography (90%) and intestinal pneumatosis on computed tomography (50%) were the most frequent imaging findings. Surgical exploration revealed intestinal ischemia (66.6%) and necrosis (46.6%), and histopathology showed ischemic and liquefactive necrosis with mixed inflammatory involvement and absence of thrombosis as the cause of AGI. CONCLUSIONS: AGI associated with severe SARS-CoV-2 infection has a high mortality rate and poses a diagnostic challenge in the ICU. The complex pathophysiology and histopathological findings indicate an associated inflammatory phenomenon as the main alteration in the absence of thrombosis, as per the intestinal biopsies of the cases studied. Further clinical studies are required to gain a better understanding of this pathology.


Subject(s)
Abdominal Injuries , COVID-19 , Thrombosis , Humans , COVID-19/complications , SARS-CoV-2 , Retrospective Studies , Thrombosis/etiology , Inflammation , Necrosis
14.
Sci Rep ; 12(1): 17248, 2022 Oct 14.
Article in English | MEDLINE | ID: covidwho-2077103

ABSTRACT

Abnormal coagulation and increased risk of thrombosis are some of the symptoms associated with COVID-19 severity. Anti-phospholipid antibodies (aPLs) present in critically ill COVID-19 patients contribute to systemic thrombosis. The aim of this study was to identify key common genes to characterize genetic crosstalk between COVID-19 and antiphospholipid syndrome (APS) using bioinformatics analysis and explore novel mechanisms of immune-mediated thrombosis in critically ill COVID-19 patients. The transcriptome data of mononuclear cells from severe COVID-19 patients and APS patients were evaluated to obtain the common genes. The protein-protein interaction network and cytoHubba module analysis in Cytoscape software were used to find the associated hinge genes and hub genes. Among the common differentially expressed genes, TIMELESS depletion was identified only in patients with severe COVID-19 and not in patients with mild COVID-19, and it was validated with the GSE159678 dataset. Functional analyses using gene ontology terms and the Kyoto Encyclopedia of Genes and Genomes pathway suggested that TIMELESS might contribute to the production of antiphospholipid antibody and thrombosis in both COVID-19 and APS patients. The potential role of TIMELESS and autophagy genes in momonuclear cells were further investigated, and GSK3B was found to be associated with TIMELESS. Autophagy targeting agents have a therapeutic potential against COVID-19 and thrombogenesis in APS, which may be related to the role of autophagy genes in the modification of circadian clock proteins. Interference with TIMELESS and other genes associated with it to regulate autoantibody expression may be a potential strategy for immunotherapy against thrombogenesis in severe COVID-19 patients.


Subject(s)
Antiphospholipid Syndrome , COVID-19 , Thrombosis , Antibodies, Antiphospholipid , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/genetics , COVID-19/genetics , Critical Illness , Humans , Thrombosis/etiology
15.
S Afr Med J ; 112(7): 472-477, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-2073605

ABSTRACT

BACKGROUND: An increased incidence of thromboembolic events in hospitalised COVID­19 patients has been demonstrated despite the use of low-molecular-weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis. OBJECTIVES: To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID­19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH. METHODS: We conducted a descriptive, cross-sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID­19 wave, in 808 hospitalised patients with confirmed COVID­19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant. RESULTS: Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 - 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 - 10.7). CONCLUSION: The bleeding risk in COVID­19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID­19.


Subject(s)
COVID-19 , Thrombosis , Anticoagulants/adverse effects , Cross-Sectional Studies , Heparin/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Humans , South Africa/epidemiology , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control
16.
Int J Mol Sci ; 23(18)2022 Sep 09.
Article in English | MEDLINE | ID: covidwho-2071501

ABSTRACT

In SARS-CoV-2-infected humans, disease progression is often associated with acute respiratory distress syndrome involving severe lung injury, coagulopathy, and thrombosis of the alveolar capillaries. The pathogenesis of these pulmonary complications in COVID-19 patients has not been elucidated. Autopsy study of these patients showed SARS-CoV-2 virions in pulmonary vessels and sequestrated leukocytes infiltrates associated with endotheliopathy and microvascular thrombosis. Since SARS-CoV-2 enters and infects target cells by binding its spike (S) protein to cellular angiotensin-converting enzyme 2 (ACE2), and there is evidence that vascular endothelial cells and neutrophils express ACE2, we investigated the effect of S-proteins and cell-cell communication on primary human lung microvascular endothelial cells (HLMEC) and neutrophils expression of thrombogenic factors and the potential mechanisms. Using S-proteins of two different SARS-CoV-2 variants (Wuhan and Delta), we demonstrate that exposure of HLMEC or neutrophils to S-proteins, co-culture of HLMEC exposed to S-proteins with non-exposed neutrophils, or co-culture of neutrophils exposed to S-proteins with non-exposed HLMEC induced transcriptional upregulation of tissue factor (TF), significantly increased the expression and secretion of factor (F)-V, thrombin, and fibrinogen and inhibited tissue factor pathway inhibitor (TFPI), the primary regulator of the extrinsic pathway of blood coagulation, in both cell types. Recombinant (r)TFPI and a thiol blocker (5,5'-dithio-bis-(2-nitrobenzoic acid)) prevented S-protein-induced expression and secretion of Factor-V, thrombin, and fibrinogen. Thrombomodulin blocked S-protein-induced expression and secretion of fibrinogen but had no effect on S-protein-induced expression of Factor-V or thrombin. These results suggests that following SARS-CoV-2 contact with the pulmonary endothelium or neutrophils and endothelial-neutrophil interactions, viral S-proteins induce coagulopathy via the TF pathway and mechanisms involving functional thiol groups. These findings suggest that using rTFPI and/or thiol-based drugs could be a viable therapeutic strategy against SARS-CoV-2-induced coagulopathy and thrombosis.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombosis , Angiotensin-Converting Enzyme 2 , Cell Communication , Endothelial Cells/metabolism , Endothelium/metabolism , Fibrinogen , Humans , Lipoproteins , Lung/metabolism , Neutrophils/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Sulfhydryl Compounds , Thrombin , Thrombomodulin , Thromboplastin , Thrombosis/etiology
18.
PLoS One ; 17(10): e0274443, 2022.
Article in English | MEDLINE | ID: covidwho-2065119

ABSTRACT

BACKGROUND: In response to reports of thrombosis with thrombocytopenia syndrome (TTS) post-vaccination, the Johnson & Johnson (J&J) vaccine was paused and then restarted in April 2021. Our objective was to assess whether this pause adversely impacted vaccine confidence. METHODS: Two large internet-based surveys were conducted in the US among adults to measure knowledge, attitudes and perceptions of the J&J vaccine pause and rates of vaccine hesitancy among unvaccinated persons before, during and after the pause. RESULTS: Among 66% of respondents aware of the pause, 44% identified blood clots as the reason for the pause without prompting. The impact of the pause on vaccine behavior among unvaccinated persons and perception of the vaccine safety system was mixed and modified by trust in the public health authorities. Those who were less willing to get vaccinated because of the pause were less inclined for all vaccines, not only the J&J product. Moreover, a notable proportion (22.1%) of the small number of persons (n = 30) vaccinated with the J&J vaccine after the pause reported not receiving information about the risk of TTS. The proportion of unvaccinated persons who were hesitant was increasing before and during the pause and then leveled off after the pause. CONCLUSIONS: The J&J vaccine pause is unlikely to be a major barrier to vaccine uptake. Public attitudes about vaccines may be more resilient than appreciated, especially when safety issues are investigated with transparent communication. This paper has important implications for messaging and program administration with future vaccine-specific adverse events. Efforts may be warranted to ensure all persons being offered the J&J vaccine are made aware of the risk of TTS.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , Ad26COVS1 , Adult , Health Knowledge, Attitudes, Practice , Humans , Parents , Thrombocytopenia/etiology , Thrombosis/etiology , Vaccination/adverse effects , Vaccination Hesitancy
20.
J Med Vasc ; 47(4): 169-174, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2061494

ABSTRACT

OBJECTIVE: To report clinical outcomes of COVID-19 related acute aortic thrombosis (AAT). METHODS: Consecutive COVID-19 patients presenting with AAT between April 2020 and August 2021 were included retrospectively. Clinical and radiological data were prospectively collected. RESULTS: Ten patients (men, 90%; mean age, 64 ± 2 years) were included. At the time of AAT diagnosis, four patients were in intensive care unit. Median time between diagnosis of COVID-19 and AAT was 5 days [IQR 0-8.5]. Clinical presentation was acute lower limb ischaemia (n=9) and mesenteric ischaemia (n=2). Thrombus localization was the abdominal aorta (n=5), the thoracic aorta (n=2) or both (n=3), with the following embolic sites: lower limbs (n=9), renal arteries (n=3), superior mesenteric artery (n=2), splenic artery (n=1), cerebral arteries (n=1). Revascularization was performed in 9 patients, using open (n=6), endovascular (n=2) or hybrid techniques (n=1). Three patients required reinterventions. The 30-day mortality was 30%. Three major amputations were performed in two patients, resulting in a free-amputation survival rate of 50% after a median follow-up of 3,5 months [IQR 2-4.1]. CONCLUSION: AAT is a rare and devastating complication of COVID-19 disease, responsible for high mortality and amputation rates.


Subject(s)
Aortic Diseases , Arterial Occlusive Diseases , COVID-19 , Thrombosis , Male , Humans , Middle Aged , Aged , Retrospective Studies , COVID-19/complications , Aortic Diseases/diagnostic imaging , Aortic Diseases/etiology , Aortic Diseases/surgery , Arterial Occlusive Diseases/surgery , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/therapy
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