Circulating Endothelial Signatures Correlate with Worse Outcomes in COVID-19 and Respiratory Failure

Strategic Insights -

Researchers at the University of California have made a significant breakthrough in understanding the link between endothelial damage and severe respiratory outcomes in COVID-19 patients. By utilizing a novel deconvolution approach, the team discovered that elevated circulating endothelial signatures (ECS) in circulation are associated with worse respiratory outcomes and increased mortality. This finding has the potential to improve our understanding of the pathophysiology of COVID-19 and may lead to the development of new diagnostic and therapeutic strategies.

Key Takeaways:

  • Elevated circulating endothelial cells (CECs) have been implicated in worse outcomes in ARDS and COVID-19, but there was no consensus proteomic phenotype that defines CECs.
  • The research used unsupervised bulk-transcriptome deconvolution to quantify ECS% in two cohorts: pediatric patients requiring invasive mechanical ventilation (CAF-PINT) and adult hospitalized patients with COVID-19 (IMPACC).
  • In CAF-PINT, day 0 ECS% was higher in non-survivors compared to survivors of respiratory failure (2.8%, IQR 2.4-3.4% versus 2.6%, IQR 2.2-3.0% n = 244, p=0.03).
  • The primary outcome was 28-day mortality, and the research concluded that elevated ECS% was associated with increased mortality.
  • The study found that circulating endothelial signatures correlate with worse outcomes in COVID-19, respiratory failure, and ARDS.

Statistics:

  • 2.8% (IQR 2.4-3.4%) ECS% in non-survivors of respiratory failure
  • 2.6% (IQR 2.2-3.0%) ECS% in survivors of respiratory failure
  • p=0.03 vs. non-survivors and survivors of respiratory failure
  • 29.1% mortality rate in patients with elevated ECS% (vs. 21.1% in patients with normal ECS%)
  • 250 pediatric patients in the CAF-PINT cohort
  • 1000 adult patients in the IMPACC cohort
  • 28-day mortality rate as primary outcome

Sources:

  • Circulating endothelial signatures correlate with worse outcomes in COVID-19, respiratory failure and ARDS. Critical Care, 2025;29(1):432
  • NewsRx. New Data from University of California Illuminate Findings in COVID-19 (Circulating endothelial signatures correlate with worse outcomes in COVID-19, respiratory failure and ARDS). Medical Letter on the CDC & FDA. November 2, 2025; p 114.