Neutrophil elastase inhibitor (Sivelestat) in the treatment of acute respiratory distress syndrome induced by COVID-19: a multicenter retrospective cohort study.

Summary

In a multicenter propensity-matched cohort of COVID-19–induced ARDS, sivelestat use was associated with better oxygenation, lower Murray lung injury scores, more ICU-free days, shorter ICU stay, and improved 28-day survival (HR 2.78; 95% CI 1.32–5.88). These findings support further randomized testing of neutrophil elastase inhibition in ARDS.

Key Findings

• In propensity-matched patients (n=158), sivelestat was associated with improved oxygenation and lower Murray lung injury scores.
• Sivelestat increased alive and ICU-free days within 28 days (HR 1.85; 95% CI 1.29–2.64; log-rank p<0.001) and shortened ICU stay.
• Overall survival improved with sivelestat (28-day HR 2.78; 95% CI 1.32–5.88; log-rank p=0.0074).

Clinical Implications

For COVID-19–related ARDS, sivelestat may be considered within clinical trials or protocolized use while awaiting RCTs; it underscores targeting neutrophil elastase–driven injury.

Limitations

• Retrospective design with potential residual confounding
• COVID-19–specific ARDS; generalizability to non–COVID-19 ARDS and optimal dosing remain uncertain

Future Directions

Conduct adequately powered RCTs of sivelestat in ARDS (COVID-19 and non–COVID-19), define optimal timing/dosing, and explore biomarkers to enrich responders.