The clinical benefit of prostacyclin treatment in mechanically ventilated patients with SARS-CoV-2 infection is not attributed to anti-inflammatory effects

BACKGROUND: Treatment with the synthetic prostacyclin analog iloprost has been shown to attenuate endothelial glycocalyx shedding and organ failure in patients with critical Covid-19. The treatment is currently being investigated in a broader setting of patients with acute respiratory failure. We here investigated the effect on inflammatory and T-cell-derived cytokine and growth-factor responses in patients with critical Covid-19. METHODS: Post-hoc analysis of a randomized controlled trial (n = 80) in mechanically ventilated patients with SARS-CoV-2 infection and concomitant endotheliopathy, defined as soluble thrombomodulin plasma-levels ≥4 ng/mL. Patients received 72 h iloprost infusion (1 ng/kg/min) or placebo. Blood samples were collected at baseline and 24 h after inclusion. Fifty-four cytokines and growth factors, distributed into six biomarker classes, were measured using the Meso Scale Discovery V-PLEX platform. RESULTS: Iloprost treatment, compared with placebo, did not result in statistically significant changes of any of the fifty-four measured biomarkers at 24 h, when adjusting for multiple testing. Likewise, linear mixed-effects models did not identify significant effects of iloprost on any of the six predefined biomarker classes at 24 h. CONCLUSIONS: In mechanically ventilated patients with SARS-CoV-2 infection and endotheliopathy, iloprost treatment had no detectable effect on inflammatory and T-cell-derived cytokine and growth-factor responses. The findings corroborate that the clinical benefit of iloprost is not attributed to anti-inflammatory effects. We suggest that future studies focus on patient selection for targeted treatment, and on combined treatment with anti-inflammatory and endothelium-stabilizing interventions, in patients with respiratory failure, hyperinflammation, and endotheliopathy.