ABSTRACT
Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is marked by coagulopathy that may relate to disease severity. Aims: We sought to understand the link between coagulopathy and acute respiratory distress syndrome (ARDS) in critically ill patients with Coronavirus Disease 2019 (COVID-19). Methods: We prospectively evaluated coagulation factor-specific biomarkers by ELISA and activity assays, viscoelastic testing by rotational thromboelastometry (ROTEM), and clinical data in 56 critically ill patients with COVID-19. One and two-way analyses of variance were performed to uncover association of factor levels with mortality, ECMO-requirement, major thrombotic events, and ARDS severity by PaO2/FiO2 ratio. Results: Patients averaged 57.2 years in age. Twenty-five percent had a major thromboembolic event, 16% had a major hemorrhage, and 23% died. All patients displayed hypercoagulability on viscoelastic testing, although those requiring veno-venous extracorporeal membrane oxygenation (ECMO) also had signs of consumptive coagulopathy and more frequent hemorrhagic complications than ECMO-naïve patients. In all patients, plasminogen activator inhibitor-1 (PAI-1) levels were increased, and ROTEM-determined clot lysis limited despite increased D-dimer levels, consistent with fibrinolytic suppression. In patients with thromboembolic events, regardless of ECMO status, PAI-1, von Willebrand Factor (vWF), and factor VIII levels were elevated. Increased PAI-1 and vWF and decreased ADAMTS13 levels correlated with ARDS severity and mortality. Conclusions: Our study defines the relationship between COVID-19 associated coagulopathy and the severity of acute lung injury by describing elevation in markers of endotheliopathy in association with low PaO2/FiO2 ratios. We identified increased PAI-1 with ARDS severity and thrombotic events, implicating fibrinolytic suppression in the microcirculatory injury and subsequent micro-and macrovascular thrombosis of severe COVID-19. Further investigation into therapeutic approaches to limit endothelial injury is needed. Other items for consideration: The study was approved by the Duke Institutional Review Board (Pro00101196 and Pro00105315).
ABSTRACT
Background: ARICA (AdheRence to Inhaled Corticosteroids in Asthma) is a comprehensive inhaled corticosteroid (ICS) adherence intervention designed to remediate each patient's unique reason for not taking their ICS as prescribed. Objective: The primary objective was to evaluate the feasibility and acceptability of implementing ARICA in a health system. Methods: 29 Black adults who self-reported ICS nonadherence, had uncontrolled persistent asthma, and a Duke Primary Care provider visit within the past 3 years were randomly assigned to intervention (N=15) or control (N=14) in a waitlist randomized controlled pilot trial. Participants were assigned to 1-3 ARICA components based on adherence barriers selected by participants;including, an asthma selfmanagement program, financial assistance referral program, and/or objective feedback on asthma control. All participants received weekly texts and emails dispelling asthma myths. Activities were delivered virtually due to COVID-19. Primary outcomes were feasibility (e.g., process outcomes) and acceptability (e.g., patient exit interviews) measured at 12 weeks. Secondary asthma (e.g., ACT) and adherence outcomes (e.g., DOSEnonadherence) were measured. Results: Most participants were female (N=27, 93%), nonsmokers (N=26, 70%), poorly controlled with ACT <15 (N=14, 48%), and mean age 49.8. Most (N=14, 93%) completed all assigned intervention components and reported mean 4.8 of 5 on Weiner feasibility, acceptability, and appropriateness of intervention. The intervention group had a greater and statistically significant improvement in ACT (Δ-3.5, CI 6.0,0.96) and Marks AQLQ (Δ 11.5, CI 5.5,17.4) when compared to changes in the control ACT (Δ-2.5, CI-5.2,0.05) and Marks AQLQ (Δ5.7, CI-1.3,12.8), respectively. The improvement in ACT in the intervention group was clinically significant. The intervention group also reported a greater and statistically significant decrease in degree of nonadherence (DOSE Δ 0.74, CI 0.2,1.3) than control (DOSE Δ 0.36, CI-0.04,0.75) and a greater decrease in the number of adherence barriers identified in the intervention group (Δ 2.1, CI 1.2,3.0) versus control group (Δ1.6, CI 0.3,3.0). The study was not powered to assess a statistically significant change between groups. Conclusion: The implementation of ARICA in a cohort of Black adults was feasibly deployed in a health system and acceptable to participants. There was a trend in improvement in asthma control and asthma quality of life and a decrease in nonadherence and barriers to adherence.
ABSTRACT
Introduction: COVID-19 is a coagulopathic disease marked by elevated d-dimers, fibrinogen, and von Willebrand factor (vWF) levels accompanying arterial and venous thrombosis. While the majority of thrombotic events associated with COVID-19 occur in hospitalized patients, a subset of patients with minimal risk factors for CVA but with positive SARS-CoV-2 testing present with stroke as presumed first manifestation of infection. It is unclear if the pro-coagulant milieu present in patients requiring hospitalization for the respiratory complications of COVID-19 is the same as that of patients who present with stroke as first symptom of disease. Methods: Following emergent revascularization, clinical vWF levels were measured in patients presenting with stroke who tested positive for COVID-19. In parallel, plasma vWF levels from 28 patients with COVID-19 requiring ICU-level care and 8 healthy volunteers were measured via ELISA. Results: Three otherwise healthy patients between the ages of 45-55 years with positive test for SARS-CoV-2 presented with large-vessel stroke. By comparison, the average age of non-COVID stroke patients was 66 years. The consistency of the clots extracted through the aspirating catheter was dark, gelatinous throughout, without evidence of calcification, and distal thrombosis was noted minutes after revascularization. The vWF level for one patient was 345%, while the other two patients had vWF levels >400% of normal, exceeding the upper limit of detection of clinical assays. In the ICU cohort, 12 of 28 had thrombotic events during hospitalization. vWF levels were elevatedby a mean of 800% over healthy controls with a range of 230-1670%. Conclusions: vWF levels were markedly elevated in both ICU patients and stroke patients withCOVID-19 with an overlapping range of elevation over healthy controls. This suggests thatwidespread endothelial inflammation accompanies infection with SARS-CoV-2 even in the absenceof respiratory symptoms.