Fibrin monomers evaluation during hospitalization for COVID-19 is a predictive marker of in-hospital mortality.

Background: Coagulopathy is one of the main triggers of severity and worsening of Coronavirus disease 2019 (COVID-19) particularly in critically ill patients. D-dimer has been widely used to detect COVID-19 coagulation disorders and has been correlated with outcomes such as disease severity and in-hospital mortality. Involvement of other fibrin degradation products, particularly fibrin monomers (FM), remains an ongoing question. Methods: We performed a monocentric study of adult patients with COVID-19, who were admitted either in the medical ward (MW) or in the intensive care unit (ICU) and who had FM measurements performed on them during the first wave of COVID-19 outbreak. We analyzed the positivity of FM levels (FM > 7 µg/mL) to assess the ability of FM monitoring during the first days of hospitalization to predict COVID-19 outcomes. Results: In our cohort, 935 FM measurements were performed in 246 patients during their first 9 days of hospitalization. During patient follow-up, the FM levels were higher in patients admitted directly to the ICU than in those admitted to the MW. Moreover, we observed significantly increased levels of FM in patients when the data were stratified for in-hospital mortality. At hospital admission, only 27 (11%) patients displayed a positive value for FM; this subgroup did not differ from other patients in terms of severity (indicated by ICU referral at admission) or in-hospital mortality. When analyzing FM positivity in the first 9 days of hospitalization, we found that 37% of patients had positive FM at least once during hospitalization and these patients had increased in-hospital mortality (p = 0.001). Thus, we used non-adjusted Kaplan-Meier curves for in-hospital mortality according to FM positivity during hospitalization and we observed a statistically significant difference for in-hospital mortality (hazard ratio = 1.48, 95% CI: 1.25-1.76, p < 0.001). However, we compared the AUC of FM positivity associated with a ratio of D-dimer >70% and found that this combined receiver operating characteristic (ROC) curve was superior to the FM positivity ROC curve alone. Conclusion: Monitoring of FM positivity in hospitalized patients with COVID-19 could be a reliable and helpful tool to predict the worsening condition and mortality of COVID-19.

D-dimer testing in clinical practice in the era of COVID-19.

D-dimer is a fragment of crosslinked fibrin resulting from plasmin cleavage of fibrin clots and hence an indirect biomarker of the hemostatic system activation. Early in the coronavirus disease 2019 (COVID-19) pandemic, several studies described coagulation disorders in affected patients, including high D-dimer levels. Consequently, D-dimer has been widely used in not-yet-approved indications. Ruling out pulmonary embolism and deep vein thrombosis in patients with low or intermediate clinical suspicion is the main application of D-dimer. D-dimer is also used to estimate the risk of venous thromboembolism recurrence and is included in the ISTH algorithm for the diagnosis of disseminated intravascular coagulation. Finally, numerous studies identified high D-dimer levels as a biomarker of poor prognosis in hospitalized patients with COVID-19. This report focuses on validated applications of D-dimer testing in patients with and without COVID-19.

Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy, antiplatelet therapy and inflammation.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with an inflammatory cytokine burst and a prothrombotic coagulopathy. Platelets may contribute to microthrombosis, and constitute a therapeutic target in COVID-19 therapy. AIM: To assess if platelet activation influences mortality in COVID-19. METHODS: We explored two cohorts of patients with COVID-19. Cohort A included 208 ambulatory and hospitalized patients with varying clinical severities and non-COVID patients as controls, in whom plasma concentrations of the soluble platelet activation biomarkers CD40 ligand (sCD40L) and P-selectin (sP-sel) were quantified within the first 48hours following hospitalization. Cohort B was a multicentre cohort of 2878 patients initially admitted to a medical ward. In both cohorts, the primary outcome was in-hospital mortality. RESULTS: In cohort A, median circulating concentrations of sCD40L and sP-sel were only increased in the 89 critical patients compared with non-COVID controls: sP-sel 40,059 (interquartile range 26,876-54,678)pg/mL; sCD40L 1914 (interquartile range 1410-2367)pg/mL (P<0.001 for both). A strong association existed between sP-sel concentration and in-hospital mortality (Kaplan-Meier log-rank P=0.004). However, in a Cox model considering biomarkers of immunothrombosis, sP-sel was no longer associated with mortality, in contrast to coagulopathy evaluated with D-dimer concentration (hazard ratio 4.86, 95% confidence interval 1.64-12.50). Moreover, in cohort B, a Cox model adjusted for co-morbidities suggested that prehospitalization antiplatelet agents had no significant impact on in-hospital mortality (hazard ratio 1.05, 95% CI 0.80-1.37; P=0.73). CONCLUSIONS: Although we observed an association between excessive biomarkers of platelet activation and in-hospital mortality, our findings rather suggest that coagulopathy is more central in driving disease progression, which may explain why prehospitalization antiplatelet drugs were not a protective factor against mortality in our multicentre cohort.

Increased Circulating CD62E+ Endothelial Extracellular Vesicles Predict Severity and in- Hospital Mortality of COVID-19 Patients.

COVID-19 and infectious diseases have been included in strategic development goals (SDG) of United Nations (UN). Severe form of COVID-19 has been described as an endothelial disease. In order to better evaluate Covid-19 endotheliopathy, we characterized several subsets of circulating endothelial extracellular vesicles (EVs) at hospital admission among a cohort of 60 patients whose severity of COVID-19 was classified at the time of inclusion. Degree of COVID-19 severity was determined upon inclusion and categorized as moderate to severe in 40 patients and critical in 20 patients. We measured citrated plasma EVs expressing endothelial membrane markers. Endothelial EVs were defined as harboring VE-cadherin (CD144+), PECAM-1 (CD31 + CD41-) or E-selectin (CD62E+). An increase in CD62E + EV levels on admission to the hospital was significantly associated with critical disease. Moreover, Kaplan-Meier survival curves for CD62E + EV level showed that level ≥ 88,053 EVs/µL at admission was a significant predictor of in hospital mortality (p = 0.004). Moreover, CD62E + EV level ≥ 88,053 EV/µL was significantly associated with higher in-hospital mortality (OR 6.98, 95% CI 2.1-26.4, p = 0.002) in a univariate logistic regression model, while after adjustment to BMI CD62E + EV level ≥ 88,053 EV/µL was always significantly associated with higher in-hospital mortality (OR 5.1, 95% CI 1.4-20.0, p = 0.01). The present findings highlight the potential interest of detecting EVs expressing E-selectin (CD62) to discriminate Covid-19 patients at the time of hospital admission and identify individuals with higher risk of fatal outcome.

Imbalance between alpha-1-antitrypsin and interleukin 6 is associated with in-hospital mortality and thrombosis during COVID-19.

Thrombosis is a hallmark of severe COVID-19. Alpha-1-antitrypsin (AAT), an inflammation-inducible serpin with anti-inflammatory, tissue protective and anticoagulant properties may be involved in severe COVID-19 pathophysiology including thrombosis onset. In this study, we examined AAT ability to predict occurrence of thrombosis and in-hospital mortality during COVID-19. To do so, we performed a monocentric cross-sectional study of 137 hospitalized patients with COVID-19 of whom 56 (41%) were critically ill and 33 (22.4%) suffered from thrombosis during hospitalization. We measured AAT and IL-6 plasma levels in all patients and phenotyped AAT in a subset of patients with or without thrombosis paired for age, sex and COVID-19 severity. We observed that AAT levels at admission were higher in both non-survivors and thrombosis patients than in survivors and non-thrombosis patients. AAT: IL-6 ratio was lower in non-survivors and thrombosis patients. In a logistic regression multivariable analysis model adjusted on age, BMI and D-dimer levels, a higher AAT: IL-6 was a protective factor of both in-hospital mortality (Odds ratio, OR: 0.07 95%CI [0.02-0.25], p < 0.001) and thrombosis (OR 0.36 95%CI [0.14-0.82], p = 0.02). AAT phenotyping did not show a higher proportion of AAT abnormal variants in thrombosis patients.Our findings suggest an insufficient production of AAT regarding inflammation intensity during severe COVID-19. AAT appeared as a powerful predictive marker of severity, mortality and thrombosis mirroring the imbalance between harmful inflammation and protective counter-balancing mechanism in COVID-19. Restoring the balance between AAT and inflammation could offer therapeutic opportunities in severe COVID-19.

D-dimer, BNP/NT-pro-BNP, and creatinine are reliable decision-making biomarkers in life-sustaining therapies withholding and withdrawing during COVID-19 outbreak.

Background: The decision for withholding and withdrawing of life-sustaining treatments (LSTs) in COVID-19 patients is currently based on a collegial and mainly clinical assessment. In the context of a global pandemic and overwhelmed health system, the question of LST decision support for COVID-19 patients using prognostic biomarkers arises. Methods: In a multicenter study in 24 French hospitals, 2878 COVID-19 patients hospitalized in medical departments from 26 February to 20 April 2020 were included. In a propensity-matched population, we compared the clinical, biological, and management characteristics and survival of patients with and without LST decision using Student's t-test, the chi-square test, and the Cox model, respectively. Results: An LST was decided for 591 COVID-19 patients (20.5%). These 591 patients with LST decision were secondarily matched (1:1) based on age, sex, body mass index, and cancer history with 591 COVID-19 patients with no LST decision. The patients with LST decision had significantly more cardiovascular diseases, such as high blood pressure (72.9 vs. 66.7%, p = 0.02), stroke (19.3 vs. 11.1%, p < 0.001), renal failure (30.4 vs. 17.4%, p < 0.001), and heart disease (22.5 vs. 14.9%, p < 0.001). Upon admission, LST patients were more severely attested by a qSOFA score ≥2 (66.5 vs. 58.8%, p = 0.03). Biologically, LST patients had significantly higher values of D-dimer, markers of heart failure (BNP and NT-pro-BNP), and renal damage (creatinine) (p < 0.001). Their evolutions were more often unfavorable (in-hospital mortality) than patients with no LST decision (41.5 vs. 10.3%, p < 0.001). By combining the three biomarkers (D-dimer, BNP and/or NT-proBNP, and creatinine), the proportion of LST increased significantly with the number of abnormally high biomarkers (24, 41.3, 48.3, and 60%, respectively, for none, one, two, and three high values of biomarkers, trend p < 0.01). Conclusion: The concomitant increase in D-dimer, BNP/NT-proBNP, and creatinine during the admission of a COVID-19 patient could represent a reliable and helpful tool for LST decision. Circulating biomarker might potentially provide additional information for LST decision in COVID-19.

Circulating Ubiquitous RNA, A Highly Predictive and Prognostic Biomarker in Hospitalized Coronavirus Disease 2019 (COVID-19) Patients.

BACKGROUND: Approximately 15-30% of hospitalized coronavirus disease 2019 (COVID-19) patients develop acute respiratory distress syndrome, systemic tissue injury, and/or multi-organ failure leading to death in around 45% of cases. There is a clear need for biomarkers that quantify tissue injury, predict clinical outcomes, and guide the clinical management of hospitalized COVID-19 patients. METHODS: We herein report the quantification by droplet-based digital polymerase chain reaction (ddPCR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia and the plasmatic release of a ubiquitous human intracellular marker, the ribonuclease P (RNase P) in order to evaluate tissue injury and cell lysis in the plasma of 139 COVID-19 hospitalized patients at admission. RESULTS: We confirmed that SARS-CoV-2 RNAemia was associated with clinical severity of COVID-19 patients. In addition, we showed that plasmatic RNase P RNAemia at admission was also highly correlated with disease severity (P < .001) and invasive mechanical ventilation status (P < .001) but not with pulmonary severity. Altogether, these results indicate a consequent cell lysis process in severe and critical patients but not systematically due to lung cell death. Finally, the plasmatic RNase P RNA value was also significantly associated with overall survival. CONCLUSIONS: Viral and ubiquitous blood biomarkers monitored by ddPCR could be useful for the clinical monitoring and the management of hospitalized COVID-19 patients. Moreover, these results could pave the way for new and more personalized circulating biomarkers in COVID-19, and more generally in infectious diseases, specific from each patient organ injury profile.

Dynamics of circulating calprotectin accurately predict the outcome of moderate COVID-19 patients.

BACKGROUND: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated. METHODS: We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death. FINDINGS: After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19. INTERPRETATION: These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit. FUNDING: The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.

Adjusting D-dimer to Lung Disease Extent to Exclude Pulmonary Embolism in COVID-19 Patients (Co-LEAD).

OBJECTIVE: D-dimer measurement is a safe tool to exclude pulmonary embolism (PE), but its specificity decreases in coronavirus disease 2019 (COVID-19) patients. Our aim was to derive a new algorithm with a specific D-dimer threshold for COVID-19 patients. METHODS: We conducted a French multicenter, retrospective cohort study among 774 COVID-19 patients with suspected PE. D-dimer threshold adjusted to extent of lung damage found on computed tomography (CT) was derived in a patient set (n = 337), and its safety assessed in an independent validation set (n = 337). RESULTS: According to receiver operating characteristic curves, in the derivation set, D-dimer safely excluded PE, with one false negative, when using a 900 ng/mL threshold when lung damage extent was <50% and 1,700 ng/mL when lung damage extent was ≥50%. In the derivation set, the algorithm sensitivity was 98.2% (95% confidence interval [CI]: 94.7-100.0) and its specificity 28.4% (95% CI: 24.1-32.3). The negative likelihood ratio (NLR) was 0.06 (95% CI: 0.01-0.44) and the area under the curve (AUC) was 0.63 (95% CI: 0.60-0.67). In the validation set, sensitivity and specificity were 96.7% (95% CI: 88.7-99.6) and 39.2% (95% CI: 32.2-46.1), respectively. The NLR was 0.08 (95% CI; 0.02-0.33), and the AUC did not differ from that of the derivation set (0.68, 95% CI: 0.64-0.72, p = 0.097). Using the Co-LEAD algorithm, 76 among 250 (30.4%) COVID-19 patients with suspected PE could have been managed without CT pulmonary angiography (CTPA) and 88 patients would have required two CTs. CONCLUSION: The Co-LEAD algorithm could safely exclude PE, and could reduce the use of CTPA in COVID-19 patients. Further prospective studies need to validate this strategy.

Severe COVID-19 is associated with hyperactivation of the alternative complement pathway

Background Severe coronavirus disease 2019 (COVID-19) is characterized by impaired type I interferon activity and a state of hyperinflammation leading to acute respiratory distress syndrome. The complement system has recently emerged as a key player in triggering and maintaining the inflammatory state, but the role of this molecular cascade in severe COVID-19 is still poorly characterized. Objective We aimed at assessing the contribution of complement pathways at both protein and transcriptomic levels. Methods To this end, we systematically assessed RNA levels of 28 complement genes in circulating whole blood of COVID-19 patients and healthy controls, including genes of the alternative pathway, for which data remain scarce. Results We found differential expression of genes involved in the complement system, yet with various expression patterns: while patients displaying moderate disease had elevated expression of classical pathway genes, severe disease was associated with increased lectin and alternative pathway activation, which correlated with inflammation and coagulopathy markers. Additionally, properdin, a pivotal positive regulator of the alternative pathway, showed high RNA expression but was found at low protein concentrations in severe and critical patients, suggesting its deposition at the sites of complement activation. Notably, low properdin levels were significantly associated with the use of mechanical ventilation (AUC = 0.82, p = 0.002). Conclusion This study sheds light on the role of the alternative pathway in severe COVID-19 and provides additional rationale for the testing of drugs inhibiting the alternative pathway of the complement system. We show that activation of the alternative complement pathway characterizes COVID-19 severity. Specifically, low properdin levels were associated with use of mechanical ventilation. This work provides a rationale for the specific inhibition of the alternative complement pathway.

Intermediate- vs. Standard-Dose Prophylactic Anticoagulation in Patients With COVID-19 Admitted in Medical Ward: A Propensity Score-Matched Cohort Study.

Background: Microthrombosis and large-vessel thrombosis are the main triggers of COVID-19 worsening. The optimal anticoagulant regimen in COVID-19 patients hospitalized in medical wards remains unknown. Objectives: To evaluate the effects of intermediate-dose vs. standard-dose prophylactic anticoagulation (AC) among patients with COVID-19 hospitalized in medical wards. Methods and results: We used a large French multicentric retrospective study enrolling 2,878 COVID-19 patients hospitalized in medical wards. After exclusion of patients who had an AC treatment before hospitalization, we generated a propensity-score-matched cohort of patients who were treated with intermediate-dose or standard-dose prophylactic AC between February 26 and April 20, 2020 (intermediate-dose, n = 261; standard-dose prophylactic anticoagulation, n = 763). The primary outcome of the study was in-hospital mortality; this occurred in 23 of 261 (8.8%) patients in the intermediate-dose group and 74 of 783 (9.4%) patients in the standard-dose prophylactic AC group (p = 0.85); while time to death was also the same in both the treatment groups (11.5 and 11.6 days, respectively, p = 0.17). We did not observe any difference regarding venous and arterial thrombotic events between the intermediate dose and standard dose, respectively (venous thrombotic events: 2.3 vs. 2.4%, p=0.99; arterial thrombotic events: 2.7 vs. 1.2%, p = 0.25). The 30-day Kaplan-Meier curves for in-hospital mortality demonstrate no statistically significant difference in in-hospital mortality (HR: 0.99 (0.63-1.60); p = 0.99). Moreover, we found that no particular subgroup was associated with a significant reduction in in-hospital mortality. Conclusion: Among COVID-19 patients hospitalized in medical wards, intermediate-dose prophylactic AC compared with standard-dose prophylactic AC did not result in a significant difference in in-hospital mortality.

Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children With Shock.

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.

Thrombus of the Aorta and SARS-CoV-2 Infection: Cause or Trigger?

Objective: Coronavirus disease 19 is a well-established cause of rare arterial thrombosis. Nevertheless, the exact mechanism of arterial thrombosis remains to be elucidated. We herein report the case of a large floating thrombus of the aortic arch, its surgical management and histological analysis. Case: A 65-year-old patient presented to the emergency department with a suspected stroke. He was non-smoker, but presented cardiovascular risk factors, namely hypertension, type 2 diabetes and hyperlipidaemia. A computed tomography of the aorta revealed a large floating thrombus of the aortic arch, at the base of the brachiocephalic trunk, suspected to be the etiology of stroke. Therapeutic anticoagulation was immediately started. The decision was made to perform an open aortic replacement surgery because of the symptomatic thromboembolic event with recent cerebral infarction and the potential harmfulness of the thrombus due to its size. A mobile thrombus was observed at the base of the brachiocephalic trunk by echocardiography. It was attached to a small area of the upper aortic wall and had an irregular surface. Histology revealed a platelet-rich thrombus lying on an aortic atherosclerotic plaque without pronounced inflammation. No plaque ulceration was present but endothelial cell desquamation was observed consistent with plaque erosion. Conclusion: In our case, there was a thrombus lying on an atherosclerotic plaque with intact thick fibrous cap, but associated with a plaque erosion mechanism. The thrombus formation appeared more likely to relate to a very localized endothelial injury.

Lupus Anticoagulant Single Positivity During the Acute Phase of COVID-19 Is Not Associated With Venous Thromboembolism or In-Hospital Mortality.

OBJECTIVE: The clinical relevance of antiphospholipid antibodies (aPLs) in COVID-19 is controversial. This study was undertaken to investigate the prevalence and prognostic value of conventional and nonconventional aPLs in patients with COVID-19. METHODS: This was a multicenter, prospective observational study in a French cohort of patients hospitalized with suspected COVID-19. RESULTS: Two hundred forty-nine patients were hospitalized with suspected COVID-19, in whom COVID-19 was confirmed in 154 and not confirmed in 95. We found a significant increase in lupus anticoagulant (LAC) positivity among patients with COVID-19 compared to patients without COVID-19 (60.9% versus 23.7%; P < 0.001), while prevalence of conventional aPLs (IgG and IgM anti-ß2 -glycoprotein I and IgG and IgM anticardiolipin isotypes) and nonconventional aPLs (IgA isotype of anticardiolipin, IgA isotype of anti-ß2 -glycoprotein I, IgG and IgM isotypes of anti-phosphatidylserine/prothrombin, and IgG and IgM isotypes of antiprothrombin) was low in both groups. Patients with COVID-19 who were positive for LAC, as compared to patients with COVID-19 who were negative for LAC, had higher levels of fibrinogen (median 6.0 gm/liter [interquartile range 5.0-7.0] versus 5.3 gm/liter [interquartile range 4.3-6.4]; P = 0.028) and C-reactive protein (CRP) (median 115.5 mg/liter [interquartile range 66.0-204.8] versus 91.8 mg/liter [interquartile range 27.0-155.1]; P = 0.019). Univariate analysis did not show any association between LAC positivity and higher risks of venous thromboembolism (VTE) (odds ratio 1.02 [95% confidence interval 0.44-2.43], P = 0.95) or in-hospital mortality (odds ratio 1.80 [95% confidence interval 0.70-5.05], P = 0.24). With and without adjustment for CRP level, age, and sex, Kaplan-Meier survival curves according to LAC positivity confirmed the absence of an association with VTE or in-hospital mortality (unadjusted P = 0.64 and P = 0.26, respectively; adjusted hazard ratio 1.13 [95% confidence interval 0.48-2.60] and 1.80 [95% confidence interval 0.67-5.01], respectively). CONCLUSION: Patients with COVID-19 have an increased prevalence of LAC positivity associated with biologic markers of inflammation. However, LAC positivity at the time of hospital admission is not associated with VTE risk and/or in-hospital mortality.