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1.
BMJ ; 376: e068407, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1612964

ABSTRACT

OBJECTIVE: To assess the effect of statin treatment versus placebo on clinical outcomes in patients with covid-19 admitted to the intensive care unit (ICU). DESIGN: INSPIRATION/INSPIRATION-S was a multicenter, randomized controlled trial with a 2×2 factorial design. Results for the anticoagulation randomization have been reported previously. Results for the double blind randomization to atorvastatin versus placebo are reported here. SETTING: 11 hospitals in Iran. PARTICIPANTS: Adults aged ≥18 years with covid-19 admitted to the ICU. INTERVENTION: Atorvastatin 20 mg orally once daily versus placebo, to be continued for 30 days from randomization irrespective of hospital discharge status. MAIN OUTCOME MEASURES: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality within 30 days from randomization. Prespecified safety outcomes included increase in liver enzyme levels more than three times the upper limit of normal and clinically diagnosed myopathy. A clinical events committee blinded to treatment assignment adjudicated the efficacy and safety outcomes. RESULTS: Of 605 patients randomized between 29 July 2020 and 4 April 2021 for statin randomization in the INSPIRATION-S trial, 343 were co-randomized to intermediate dose versus standard dose prophylactic anticoagulation with heparin based regimens, whereas 262 were randomized after completion of the anticoagulation study. 587 of the 605 participants were included in the primary analysis of INSPIRATION-S, reported here: 290 were assigned to atorvastatin and 297 to placebo (median age 57 years (interquartile range 45-68 years); 256 (44%) women). The primary outcome occurred in 95 (33%) patients assigned to atorvastatin and 108 (36%) assigned to placebo (odds ratio 0.84, 95% confidence interval 0.58 to 1.21). Death occurred in 90 (31%) patients in the atorvastatin group and 103 (35%) in the placebo group (odds ratio 0.84, 95% confidence interval 0.58 to 1.22). Rates for venous thromboembolism were 2% (n=6) in the atorvastatin group and 3% (n=9) in the placebo group (odds ratio 0.71, 95% confidence interval 0.24 to 2.06). Myopathy was not clinically diagnosed in either group. Liver enzyme levels were increased in five (2%) patients assigned to atorvastatin and six (2%) assigned to placebo (odds ratio 0.85, 95% confidence interval 0.25 to 2.81). CONCLUSIONS: In adults with covid-19 admitted to the ICU, atorvastatin was not associated with a significant reduction in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality compared with placebo. Treatment was, however, found to be safe. As the overall event rates were lower than expected, a clinically important treatment effect cannot be excluded. TRIAL REGISTRATION: ClinicalTrials.gov NCT04486508.


Subject(s)
Anticoagulants/therapeutic use , Atorvastatin/therapeutic use , COVID-19/complications , Critical Care/methods , Venous Thromboembolism/epidemiology , Adolescent , Adult , Aged , COVID-19/mortality , Critical Care/statistics & numerical data , Double-Blind Method , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Heparin/therapeutic use , Humans , Intensive Care Units , Iran/epidemiology , Male , Middle Aged , Odds Ratio , SARS-CoV-2 , Treatment Outcome , Venous Thromboembolism/prevention & control , Venous Thromboembolism/virology , Young Adult
3.
Circ J ; 85(12): 2208-2214, 2021 11 25.
Article in English | MEDLINE | ID: covidwho-1533392

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) reportedly causes venous thromboembolism (VTE), but the status of this complication in Japan was unclear.Methods and Results:The VTE and COVID-19 in Japan Study is a retrospective, multicenter cohort study enrolling hospitalized patients with COVID-19 who were evaluated with contrast-enhanced computed tomography (CT) examination at 22 centers in Japan between March 2020 and October 2020. Among 1,236 patients with COVID-19, 45 (3.6%) were evaluated with contrast-enhanced CT examination. VTE events occurred in 10 patients (22.2%), and the incidence of VTE in mild, moderate, and severe COVID-19 was 0%, 11.8%, and 40.0%, respectively. COVID-19 patients with VTE showed a higher body weight (81.6 vs. 64.0 kg, P=0.005) and body mass index (26.9 vs. 23.2 kg/m2, P=0.04), and a higher proportion had a severe status for COVID-19 compared with those without. There was no significant difference in the proportion of patients alive at discharge between patients with and without VTE (80.0% vs. 88.6%, P=0.48). Among 8 pulmonary embolism (PE) patients, all were low-risk PE. CONCLUSIONS: Among a relatively small number of patients undergoing contrast-enhanced CT examination in Japanese real-world clinical practice, there were no VTE patients among those with mild COVID-19, but the incidence of VTE seemed to be relatively high among severe COVID-19 patients, although all PE events were low-risk without significant effect on mortality risk.


Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , COVID-19/complications , Humans , Incidence , Japan/epidemiology , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/epidemiology , Pulmonary Embolism/virology , Retrospective Studies , Risk Factors , Venous Thromboembolism/epidemiology , Venous Thromboembolism/virology
4.
J Thromb Thrombolysis ; 52(4): 999-1006, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1525574

ABSTRACT

A high incidence of thrombosis in hospitalised patients with COVID-19 was identified early during the pandemic. Accurately quantifying thrombotic risk may assist prognosis and guide appropriate thromboprophylaxis. Observational studies have estimated the rate of thrombosis in both hospitalised and non-hospitalised patients with COVID-19, and how this corresponds to the severity of illness. In this review, we provide an overview of the incidence and prevalence of arterial and venous thrombotic events in patients with COVID-19 and highlight the limitations in the studies to date. Asymptomatic individuals with COVID-19 and those with mild symptoms are at very low risk of thrombotic complications. However, rates of thrombosis are substantially increased in hospitalised patients, and are strikingly high in those patients who are critically-ill requiring treatment on the intensive care unit and especially those requiring extracorporeal membrane oxygenation. Clinicians managing such patients need to be aware of these risks and take appropriate steps with respect to thromboprophylaxis and heightened clinical vigilance. Large prospective observational studies will more accurately quantify thrombotic rate, and randomized controlled trials are currently investigating optimal thromboprophylactic strategies.


Subject(s)
COVID-19 , Thrombosis , Venous Thromboembolism , Anticoagulants , Biomarkers , COVID-19/complications , Humans , Incidence , Observational Studies as Topic , Thrombosis/epidemiology , Thrombosis/virology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/virology
5.
J Thromb Thrombolysis ; 52(4): 985-991, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1525573

ABSTRACT

Pulmonary thromboembolism and deep venous thrombosis occur frequently in hospitalised patients with COVID-19, the prevalence increases on the intensive care unit (ICU) and is very high in patients on extracorporeal membrane oxygenation (ECMO). We undertook a literature review to assess the usefulness of screening for peripheral venous thrombosis or pulmonary thrombosis in patients admitted with COVID-19. Outside of the ICU setting, D-dimer elevation on presentation or marked increase from baseline should alert the need for doppler ultrasound scan of the lower limbs. In the ICU setting, consideration should be given to routine screening with doppler ultrasound, given the high prevalence of thrombosis in this cohort despite standard anticoagulant thromboprophylaxis. However, absence of lower limb thrombosis on ultrasound does not exclude pulmonary venous thrombosis. Screening with CT pulmonary angiography (CTPA) is not justified in patients on the general wards, unless there are clinical features and/or marked elevations in markers of COVID-19-associated coagulopathy. However, the risk of pulmonary embolism or pulmonary thrombosis in ICU patients is very high, especially in patients on ECMO, where studies that employed routine screening for thrombosis with CT scanning have uncovered up to 100% incidence of pulmonary thrombosis despite standard anticoagulant thromboprophylaxis. Therefore, in patients at low bleeding risk and high clinical suspicion of venous thromboembolism, therapeutic anticoagulation should be considered even before screening, Our review highlights the need for increased vigilance for VTE, with a low threshold for doppler ultrasound and CTPA in high risk in-patient cohorts, where clinical features and D-dimer levels may not accurately reflect the occurrence of pulmonary thromboembolism.


Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Anticoagulants/therapeutic use , COVID-19/complications , Humans , Pulmonary Embolism/diagnosis , Pulmonary Embolism/virology , Venous Thromboembolism/diagnosis , Venous Thromboembolism/virology
7.
Obstet Gynecol ; 137(4): 571-580, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1322672

ABSTRACT

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. METHODS: We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. RESULTS: A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race-ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2-11%) incidence of venous thromboembolism among those with severe-critical illness compared with 0.2% in mild-moderate and 0% in asymptomatic (P<.001 for trend across severity). In adjusted analyses, severe-critical COVID-19 was associated with increased risk of cesarean birth (59.6% vs 34.0%, adjusted relative risk [aRR] 1.57, 95% CI 1.30-1.90), hypertensive disorders of pregnancy (40.4% vs 18.8%, aRR 1.61, 95% CI 1.18-2.20), and preterm birth (41.8% vs 11.9%, aRR 3.53, 95% CI 2.42-5.14) compared with asymptomatic patients. Mild-moderate COVID-19 was not associated with adverse perinatal outcomes compared with asymptomatic patients. CONCLUSION: Compared with pregnant patients with SARS-CoV-2 infection without symptoms, those with severe-critical COVID-19, but not those with mild-moderate COVID-19, were at increased risk of perinatal complications.


Subject(s)
COVID-19/epidemiology , Patient Acuity , Pregnancy Complications, Infectious/epidemiology , Adult , Asymptomatic Infections , Body Mass Index , COVID-19/complications , COVID-19/diagnosis , Cesarean Section/statistics & numerical data , Cohort Studies , Comorbidity , Female , Humans , Hypertension, Pregnancy-Induced/epidemiology , Infant, Newborn , Maternal Age , Maternal Mortality , Perinatal Mortality , Pregnancy , Pregnancy Complications, Infectious/virology , Premature Birth/epidemiology , Risk Factors , SARS-CoV-2 , United States/epidemiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/virology , Young Adult
8.
J Thromb Haemost ; 18(7): 1743-1746, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317987

ABSTRACT

BACKGROUND: Coagulopathy is a common abnormality in patients with COVID-19. However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID-19 patients. OBJECTIVES: Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID-19 patients. PATIENTS AND METHODS: We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care. A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID-19. Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis. Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation. Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration. RESULTS: From March 19 to April 11, 2020, 26 consecutive patients with severe COVID-19 were screened for VTE. Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation. The overall rate of VTE in patients was 69%. The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03). Surprisingly, we found a high rate of thromboembolic events in COVID-19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms. CONCLUSION: Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID-19 patients.


Subject(s)
Anticoagulants/therapeutic use , Betacoronavirus/pathogenicity , Blood Coagulation/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Pulmonary Embolism/prevention & control , Venous Thromboembolism/prevention & control , Venous Thrombosis/prevention & control , Aged , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , France/epidemiology , Host-Parasite Interactions , Humans , Incidence , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Pulmonary Embolism/blood , Pulmonary Embolism/epidemiology , Pulmonary Embolism/virology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome , Venous Thromboembolism/blood , Venous Thromboembolism/epidemiology , Venous Thromboembolism/virology , Venous Thrombosis/blood , Venous Thrombosis/epidemiology , Venous Thrombosis/virology
9.
Rev Cardiovasc Med ; 22(2): 277-286, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1310348

ABSTRACT

Emerging evidences prove that the ongoing pandemic of coronavirus disease 2019 (COVID-19) is strictly linked to coagulopathy even if pneumonia appears as the major clinical manifestation. The exact incidence of thromboembolic events is largely unknown, so that a relative significant number of studies have been performed in order to explore thrombotic risk in COVID-19 patients. Cytokine storm, mediated by pro-inflammatory interleukins, tumor necrosis factor α and elevated acute phase reactants, is primarily responsible for COVID-19-associated hypercoagulopathy. Also comorbidities, promoting endothelial dysfunction, contribute to a higher thromboembolic risk. In this review we aim to investigate epidemiology and clarify the pathophysiological pathways underlying hypercoagulability in COVID-19 patients, providing indications on the prevention of thromboembolic events in COVID-19. Furthermore we aim to reassume the pathophysiological paths involved in COVID-19 infection.


Subject(s)
Blood Coagulation , COVID-19/blood , Pulmonary Embolism/blood , Venous Thromboembolism/blood , Venous Thrombosis/blood , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , Host-Pathogen Interactions , Humans , Prognosis , Pulmonary Embolism/epidemiology , Pulmonary Embolism/prevention & control , Pulmonary Embolism/virology , Risk Assessment , Risk Factors , SARS-CoV-2/pathogenicity , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control , Venous Thromboembolism/virology , Venous Thrombosis/epidemiology , Venous Thrombosis/prevention & control , Venous Thrombosis/virology
10.
Clin Appl Thromb Hemost ; 27: 10760296211013104, 2021.
Article in English | MEDLINE | ID: covidwho-1282217

ABSTRACT

This study aimed to assess the clinical features of coronavirus disease 2019 (COVID-19) patients with VTE, to help develop preventive measures for venous thromboembolism (VTE in COVID-19) cases. COVID-19 patients admitted to Henan Provincial People's Hospital were retrospectively analyzed, including 23, 4 and 8 cases with mild to moderate, severe and critical symptoms, respectively. VTE incidence, age at onset, relevant laboratory parameters and prognosis were analyzed. Overall, VTE incidence in the 35 patients was 20.0%, occurring in severe (n = 1) and critical (n = 6) cases. D-dimer showed statistical significance in laboratory examination, representing except a diagnostic index and especial can be a prognostic factor in VTE among COVID-19 patients. Severe and critical COVID-19 cases had significantly reduced platelet counts, with a risk of hemorrhage. During treatment, the risk of both hemorrhage and thrombosis should be considered. VTE occurs in COVID-19 cases, affecting individuals with severe and critical symptoms. Significant D-dimer increase is of great significance in the risk assessment of death in critical cases of COVID-19. Appropriate measures should be taken to prevent VTE during treatment.


Subject(s)
COVID-19/virology , Fibrin Fibrinogen Degradation Products/analysis , Venous Thromboembolism/virology , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , COVID-19/therapy , China/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Platelet Count , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Venous Thromboembolism/blood , Venous Thromboembolism/mortality , Venous Thromboembolism/prevention & control , Young Adult
11.
J Thromb Thrombolysis ; 52(4): 999-1006, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1245702

ABSTRACT

A high incidence of thrombosis in hospitalised patients with COVID-19 was identified early during the pandemic. Accurately quantifying thrombotic risk may assist prognosis and guide appropriate thromboprophylaxis. Observational studies have estimated the rate of thrombosis in both hospitalised and non-hospitalised patients with COVID-19, and how this corresponds to the severity of illness. In this review, we provide an overview of the incidence and prevalence of arterial and venous thrombotic events in patients with COVID-19 and highlight the limitations in the studies to date. Asymptomatic individuals with COVID-19 and those with mild symptoms are at very low risk of thrombotic complications. However, rates of thrombosis are substantially increased in hospitalised patients, and are strikingly high in those patients who are critically-ill requiring treatment on the intensive care unit and especially those requiring extracorporeal membrane oxygenation. Clinicians managing such patients need to be aware of these risks and take appropriate steps with respect to thromboprophylaxis and heightened clinical vigilance. Large prospective observational studies will more accurately quantify thrombotic rate, and randomized controlled trials are currently investigating optimal thromboprophylactic strategies.


Subject(s)
COVID-19 , Thrombosis , Venous Thromboembolism , Anticoagulants , Biomarkers , COVID-19/complications , Humans , Incidence , Observational Studies as Topic , Thrombosis/epidemiology , Thrombosis/virology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/virology
12.
J Thromb Thrombolysis ; 52(4): 985-991, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1237541

ABSTRACT

Pulmonary thromboembolism and deep venous thrombosis occur frequently in hospitalised patients with COVID-19, the prevalence increases on the intensive care unit (ICU) and is very high in patients on extracorporeal membrane oxygenation (ECMO). We undertook a literature review to assess the usefulness of screening for peripheral venous thrombosis or pulmonary thrombosis in patients admitted with COVID-19. Outside of the ICU setting, D-dimer elevation on presentation or marked increase from baseline should alert the need for doppler ultrasound scan of the lower limbs. In the ICU setting, consideration should be given to routine screening with doppler ultrasound, given the high prevalence of thrombosis in this cohort despite standard anticoagulant thromboprophylaxis. However, absence of lower limb thrombosis on ultrasound does not exclude pulmonary venous thrombosis. Screening with CT pulmonary angiography (CTPA) is not justified in patients on the general wards, unless there are clinical features and/or marked elevations in markers of COVID-19-associated coagulopathy. However, the risk of pulmonary embolism or pulmonary thrombosis in ICU patients is very high, especially in patients on ECMO, where studies that employed routine screening for thrombosis with CT scanning have uncovered up to 100% incidence of pulmonary thrombosis despite standard anticoagulant thromboprophylaxis. Therefore, in patients at low bleeding risk and high clinical suspicion of venous thromboembolism, therapeutic anticoagulation should be considered even before screening, Our review highlights the need for increased vigilance for VTE, with a low threshold for doppler ultrasound and CTPA in high risk in-patient cohorts, where clinical features and D-dimer levels may not accurately reflect the occurrence of pulmonary thromboembolism.


Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Anticoagulants/therapeutic use , COVID-19/complications , Humans , Pulmonary Embolism/diagnosis , Pulmonary Embolism/virology , Venous Thromboembolism/diagnosis , Venous Thromboembolism/virology
13.
Arthritis Rheumatol ; 73(6): 914-920, 2021 06.
Article in English | MEDLINE | ID: covidwho-1210637

ABSTRACT

OBJECTIVE: Patients with systemic autoimmune rheumatic diseases (ARDs) continue to be concerned about risks of severe coronavirus disease 2019 (COVID-19) outcomes. This study was undertaken to evaluate the risks of severe outcomes in COVID-19 patients with systemic ARDs compared to COVID-19 patients without systemic ARDs. METHODS: Using a large multicenter electronic health record network, we conducted a comparative cohort study of patients with systemic ARDs diagnosed as having COVID-19 (identified by diagnostic code or positive molecular test result) compared to patients with COVID-19 who did not have systemic ARDs, matched for age, sex, race/ethnicity, and body mass index (primary matched model) and additionally matched for comorbidities and health care utilization (extended matched model). Thirty-day outcomes were assessed, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation, acute renal failure requiring renal replacement therapy, ischemic stroke, venous thromboembolism, and death. RESULTS: We initially identified 2,379 COVID-19 patients with systemic ARDs (mean age 58 years; 79% female) and 142,750 comparators (mean age 47 years; 54% female). In the primary matched model (2,379 patients with systemic ARDs and 2,379 matched comparators with COVID-19 without systemic ARDs), patients with systemic ARDs had a significantly higher risk of hospitalization (relative risk [RR] 1.14 [95% confidence interval (95% CI) 1.03-1.26]), ICU admission (RR 1.32 [95% CI 1.03-1.68]), acute renal failure (RR 1.81 [95% CI 1.07-3.07]), and venous thromboembolism (RR 1.74 [95% CI 1.23-2.45]) versus comparators but did not have a significantly higher risk of mechanical ventilation or death. In the extended model, all risks were largely attenuated, except for the risk of venous thromboembolism (RR 1.60 [95% CI 1.14-2.25]). CONCLUSION: Our findings indicate that COVID-19 patients with systemic ARDs may be at a higher risk of hospitalization, ICU admission, acute renal failure, and venous thromboembolism when compared to COVID-19 patients without systemic ARDs. These risks may be largely mediated by comorbidities, except for the risk of venous thromboembolism.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Rheumatic Diseases/epidemiology , SARS-CoV-2 , Acute Kidney Injury/epidemiology , Acute Kidney Injury/virology , Cohort Studies , Comorbidity , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Odds Ratio , Renal Replacement Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Rheumatic Diseases/virology , Risk Factors , United States/epidemiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/virology
14.
Viruses ; 13(5)2021 04 26.
Article in English | MEDLINE | ID: covidwho-1201364

ABSTRACT

The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19). We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients. In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion. Baseline data, laboratory biomarkers, treatments, and outcomes were collected. Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively. A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55-77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed. PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6-4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1-537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4-29.5]). The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5-67.8], p < 0.01). In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively.


Subject(s)
COVID-19/pathology , Fibrin Fibrinogen Degradation Products/metabolism , Neutrophils/pathology , Pulmonary Embolism/virology , Aged , COVID-19/blood , Computed Tomography Angiography , Female , Humans , Logistic Models , Male , Middle Aged , Prognosis , Pulmonary Embolism/blood , Pulmonary Embolism/pathology , Retrospective Studies , Risk Factors , SARS-CoV-2/genetics , Venous Thromboembolism/blood , Venous Thromboembolism/pathology , Venous Thromboembolism/virology
15.
Arch Med Res ; 52(3): 252-260, 2021 04.
Article in English | MEDLINE | ID: covidwho-1188296

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is complicated by significant coagulopathy, that manifests in the form of both pulmonary artery microthromboses and systemic venous thromboembolism (VTE) leading to excess mortality. Dysregulated innate immune response in the lung due to viral-entry mediated angiotensin-I-converting enzyme 2 (ACE2) receptor downregulation causes endothelial injury in the pulmonary vasculature, inflammatory cytokine release, increased thrombin generation and impaired fibrinolysis. The inflammatory disease process, immobilization with prolonged hospital stay, hypoxia due to extensive lung injury and pre-existing comorbidities can contribute to thromboembolic episodes (TE). The observed risk for TE in COVID-19 is high despite anticoagulation, particularly in intensive care unit (ICU) patients. A high level of clinical suspicion, lower threshold for diagnostic imaging and aggressive early and extended thromboprophylaxis is indicated. The available evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is heterogenous, but rapidly evolving. We propose an evidence-based, risk-stratified protocol in approaching the risk of TE episodes in COVID-19 patients.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/blood , Venous Thromboembolism/drug therapy , Venous Thromboembolism/virology , COVID-19/pathology , Evidence-Based Practice , Humans , SARS-CoV-2/isolation & purification , Venous Thromboembolism/pathology
16.
Expert Rev Anti Infect Ther ; 19(11): 1397-1413, 2021 11.
Article in English | MEDLINE | ID: covidwho-1174805

ABSTRACT

INTRODUCTION: SARS-CoV-2, the causative agent of COVID-19, attacks the immune system causing an exaggerated and uncontrolled release of pro-inflammatory mediators (cytokine storm). Recent studies propose an active role of coagulation disorders in disease progression. This hypercoagulability has been displayed by marked increase in D-dimer in hospitalized patients. AREAS COVERED: This review summarizes the pathogenesis of SARS-CoV-2 infection, generation of cytokine storm, the interdependence between inflammation and coagulation, its consequences and the possible management options for coagulation complications like venous thromboembolism (VTE), microthrombosis, disseminated intravascular coagulation (DIC), and systemic and local coagulopathy. We searched PubMed, Scopus, and Google Scholar for relevant reports using COVID-19, cytokine storm, and coagulation as keywords. EXPERT OPINION: A prophylactic dose of 5000-7500 units of low molecular weight heparin (LMWH) has been recommended for hospitalized COVID-19 patients in order to prevent VTE. Treatment dose of LMWH, based on disease severity, is being contemplated for patients showing a marked rise in levels of D-dimer due to possible pulmonary thrombi. Additionally, targeting PAR-1, thrombin, coagulation factor Xa and the complement system may be potentially useful in reducing SARS-CoV-2 infection induced lung injury, microvascular thrombosis, VTE and related outcomes like DIC and multi-organ failure.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Cytokine Release Syndrome , Venous Thromboembolism , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/virology , COVID-19/complications , Cytokine Release Syndrome/virology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Venous Thromboembolism/drug therapy , Venous Thromboembolism/virology
17.
J Infect Dis ; 223(6): 933-944, 2021 03 29.
Article in English | MEDLINE | ID: covidwho-1155780

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection is associated with hypercoagulability, which predisposes to venous thromboembolism (VTE). We analyzed platelet and neutrophil activation in patients with coronavirus disease 2019 (COVID-19) and their association with VTE. METHODS: Hospitalized patients with COVID-19 and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase 9, a neutrophil-released enzyme, were measured. Four patients were restudied after recovery. The activating effect of plasma from patients with COVID-19 on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied. RESULTS: A total of 36 patients with COVID-19 and 31 healthy controls were studied; VTE developed in 8 of 36 patients with COVID-19 (22.2%). Platelets and neutrophils were activated in patients with COVID-19. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic matrix metalloproteinase 9 was significantly increased in patients with COVID-19. Platelet and neutrophil activation markers, but less so NETs, normalized after recovery. In vitro, plasma from patients with COVID-19 triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic-dose low-molecular-weight heparin, but not by aspirin or dypiridamole. CONCLUSIONS: Platelet and neutrophil activation are key features of patients with COVID-19. NET biomarkers may help to predict clinical worsening and VTE and may guide low-molecular-weight heparin treatment.


Subject(s)
COVID-19/blood , COVID-19/immunology , Thrombosis/blood , Thrombosis/immunology , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Blood Platelets/immunology , COVID-19/virology , Extracellular Traps , Female , Heparin, Low-Molecular-Weight/blood , Humans , Male , Matrix Metalloproteinase 9/blood , Middle Aged , Neutrophil Activation , Neutrophils/immunology , Platelet Activation , SARS-CoV-2/isolation & purification , Thrombosis/virology , Venous Thromboembolism/blood , Venous Thromboembolism/immunology , Venous Thromboembolism/virology
18.
J Appl Lab Med ; 6(4): 953-961, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1147984

ABSTRACT

BACKGROUND: Numerous studies have documented reduced access to patient care due to the COVID-19 pandemic, including access to diagnostic or screening tests, prescription medications, and treatment for an ongoing condition. In the context of clinical management for venous thromboembolism, this could result in suboptimal therapy with warfarin. We aimed to determine the impact of the pandemic on utilization of International Normalized Ratio (INR) testing and the percentage of high and low results. METHODS: INR data from 11 institutions were extracted to compare testing volume and the percentage of INR results ≥3.5 and ≤1.5 between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (January-June 2020, period 2). The analysis was performed for inpatient and outpatient cohorts. RESULTS: Testing volumes showed relatively little change in January and February, followed by a significant decrease in March, April, and May, and then returned to baseline in June. Outpatient testing showed a larger percentage decrease in testing volume compared to inpatient testing. At 10 of the 11 study sites, we observed an increase in the percentage of abnormal high INR results as test volumes decreased, primarily among outpatients. CONCLUSION: The COVID-19 pandemic impacted INR testing among outpatients which may be attributable to several factors. Increased supratherapeutic INR results during the pandemic period when there was reduced laboratory utilization and access to care is concerning because of the risk of adverse bleeding events in this group of patients. This could be mitigated in the future by offering drive-through testing and/or widespread implementation of home INR monitoring.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , International Normalized Ratio/methods , Patient Care/statistics & numerical data , Patient Care/standards , SARS-CoV-2/isolation & purification , Venous Thromboembolism/drug therapy , Warfarin/therapeutic use , COVID-19/virology , Humans , Venous Thromboembolism/virology
19.
J Vasc Surg Venous Lymphat Disord ; 9(6): 1371-1381.e4, 2021 11.
Article in English | MEDLINE | ID: covidwho-1142108

ABSTRACT

OBJECTIVE: The study aimed to validate the original Caprini score and its modifications considering coronavirus disease (COVID-19) as a severe prothrombotic condition in patients admitted to the hospital. METHODS: The relevant data were extracted from the electronic medical records with an implemented Caprini score and were retrospectively evaluated. The score was calculated twice: by the physician on admission and by the investigator at discharge (death). The final assessment considered additional risk factors that occurred during inpatient treatment. Besides the original Caprini score (a version of 2005), the modified version added the elevation of D-dimer and specific scores for COVID-19 as follows: two points for asymptomatic, three points for symptomatic, and five points for symptomatic infection with positive D-dimer. Cases were evaluated retrospectively. The primary end point was symptomatic venous thromboembolism (VTE) detected during inpatient treatment and confirmed by appropriate imaging testing or autopsy. The secondary end points included those observed during hospitalization (admission to the intensive care unit, a requirement for invasive mechanical ventilation, death, bleeding), and those assessed at 6-month follow-up (symptomatic VTE, bleeding, death). The association of eight different versions of the Caprini score with VTE events was evaluated. RESULTS: A total of 168 patients (83 males and 85 females at the age of 58.3 ± 12.7 years) were admitted to the hospital between April 30 and May 29, 2020, and were discharged or died to the time of data analysis. The original Caprini score varied between 2 and 12 (5.4 ± 1.8) at the admission and between 2 and 15 (5.9 ± 2.5) at discharge or death. The maximal score was observed with modification including specific COVID-19 points of 5 to 20 (10.0 ± 3.0). Patients received prophylactic (enoxaparin 40 mg once daily: 2.4%), intermediate (enoxaparin 80 mg once daily: 76.8%), or therapeutic (enoxaparin 1 mg/kg twice daily: 20.8%) anticoagulation. Despite this, symptomatic VTE was detected in 11 (6.5%) inpatients. Of the 168 individuals, 28 (16.7%) admitted to the intensive care unit, 8 (4.8%) required invasive mechanical ventilation, and 8 (4.8%) died. Clinically relevant nonmajor bleeding was detected in two (1.2%) cases. The Caprini score of all eight versions demonstrated a significant association with inpatient VTE frequency. The highest predictability was observed for the original scale when assessed at discharge (death). Only symptomatic VTE was reported after discharge with a cumulative incidence of 7.1%. This did not affect the predictability of the Caprini score. Extended antithrombotic treatment was prescribed to 49 (29%) patients with a cumulative incidence of bleeding of 1.8% at 6 months. CONCLUSIONS: The study identified a significant correlation between the Caprini score and the risk of VTE in patients with COVID-19. All models including specific COVID-19 scores showed equally high predictability, and use of the original Caprini score is appropriate for patients with COVID-19.


Subject(s)
COVID-19/complications , Venous Thromboembolism/diagnosis , Venous Thromboembolism/virology , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/diagnosis , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Risk Factors , Russia , Venous Thromboembolism/epidemiology , Young Adult
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