Background Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis. Objectives To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients. Methods Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ≤ 48 h following admission.Results Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWF:Ag) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428-596) compared to non-critical patients (288%, 230-350, p < 0.0001) or COVID-19 outpatients (144%, 133-198, p = 0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86-1.09) compared to non-critical patients (0.96, 1.04-1.39, p < 0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWF:Ag cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWF:Ag was further confirmed in a Kaplan-Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and d-dimer levels. Conclusion VWF:Ag is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.

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–β2‐glycoprotein I and IgG and IgM anticardiolipin isotypes) and nonconventional aPLs (IgA isotype of anticardiolipin, IgA isotype of anti‐β2‐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.