Influence of Increasing Age and Body Mass Index of Gender in COVID-19 Patients.

Background: The impact of gender on outcomes in patients suffering from coronavirus disease 2019 (COVID-19) is frequently debated. However, the synchronous influence of additional risk factors is seldom mentioned. With increasing emphasis on identifying patients who are at risk of complications from COVID-19, we decided to conduct a retrospective review to assess the influence of age and body mass index (BMI) on gender-based differences in outcomes. Materials and Methods: A retrospective review of 1288 patients was conducted at a tertiary care hospital. Binary logistic regression was used to assess differences in risk factors and outcomes between genders. The associations between predictors and outcomes were described using odds ratios in tables, forest plots, and regression curves plotted using Sigma Plot. Results: Majority of patients were women (53.6% vs. 46.4%). Median BMI in men was higher than women (p = 0.003). Key predictors for all-cause morbidity/mortality in men were diabetes, chronic kidney disease, and regular use of angiotensin-converting enzyme inhibitors. In women, age >65 and regular use of inhaled steroid were additional risk factors. Men had a higher risk of acute respiratory distress syndrome (2.83 [1.70-4.70]), acute renal failure (1.96 [1.20-3.20]), and had a longer length of stay (0.11 [1.52]). Obesity has a stronger bearing on outcomes in women, and age has a more pronounced effect on outcomes in men. Conclusion: Extremes of BMI and older age are associated with worse outcomes in both men and women. Obesity has a stronger bearing on outcomes of COVID-19 infection in women, while the effect of older age on outcomes is more pronounced in men.

Tie2 activation protects against prothrombotic endothelial dysfunction in COVID-19.

Endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. Constitutively, the endothelial surface is anticoagulant, a property maintained at least in part via signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift. We sought to assess whether severe COVID-19 is associated with procoagulant endothelial dysfunction and alterations in the Tie2/angiopoietin axis. Primary HUVECs treated with plasma from patients with severe COVID-19 upregulated the expression of thromboinflammatory genes, inhibited the expression of antithrombotic genes, and promoted coagulation on the endothelial surface. Pharmacologic activation of Tie2 with the small molecule AKB-9778 reversed the prothrombotic state induced by COVID-19 plasma in primary endothelial cells. Lung autopsies from patients with COVID-19 demonstrated a prothrombotic endothelial signature. Assessment of circulating endothelial markers in a cohort of 98 patients with mild, moderate, or severe COVID-19 revealed endothelial dysfunction indicative of a prothrombotic state. Angpt-2 concentrations rose with increasing disease severity, and the highest levels were associated with worse survival. These data highlight the disruption of Tie2/angiopoietin signaling and procoagulant changes in endothelial cells in severe COVID-19. Our findings provide rationale for current trials of Tie2-activating therapy with AKB-9778 in COVID-19.