# Long-Term Hemostatic and Endothelial Dysregulation Associated with Cardiovascular Events in Survivors of COVID-19 Previously Admitted to the ICU

## TL;DR

This study finds that long-term imbalances in blood clotting and endothelial function are linked to cardiovascular issues in ICU-discharged COVID-19 survivors.

## Contribution

The study identifies novel associations between hemostatic and endothelial proteins and cardiovascular events in long-term COVID-19 survivors.

## Key findings

- Lower levels of factor IX, protein C, and protein S are associated with cardiovascular events one year after ICU discharge.
- Higher von Willebrand factor levels correlate with elevated NT-proBNP, indicating endothelial dysfunction.
- Gender-specific patterns were observed in the associations between proteins and NT-proBNP levels.

## Abstract

Post-acute sequelae of COVID-19 have been associated with an elevated risk of thromboembolism and adverse cardiovascular events (CVEs). We aim to evaluate whether alterations in poorly studied hemostatic and endothelial proteins are associated with CVEs in patients previously admitted to the ICU and evaluated one year post-discharge. We carried out a cross-sectional study involving 63 COVID-19 patients previously admitted to the ICU one year post-discharge. Plasma levels of factor IX (coagulation factor), protein C, protein S (natural anticoagulant), and von Willebrand factor (VWF, an endothelial marker) were measured using a Luminex 200™ analyzer. Generalized linear models (GLMs) were used to assess the association of these coagulation proteins with CVEs and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We found that lower levels of factor IX (p = 0.011), protein C (p = 0.028), and protein S (p = 0.008) were associated with CVEs one year after ICU discharge. Additionally, at the one-year follow-up, we found lower levels of factor IX (p = 0.002) and higher levels of VWF (p = 0.006) associated with higher levels of NT-proBNP, underscoring the involvement of both hemostatic imbalance and persistent endothelial dysfunction. Our findings revealed a gender-specific pattern of associations with NT-proBNP levels. These findings highlight the significant role of persistent hemostatic imbalance and endothelial dysfunction in the development of cardiovascular abnormalities among COVID-19 survivors discharged from the ICU.