Extracellular matrix turnover in severe COVID-19 is reduced by corticosteroids.

Summary

In a multicenter prospective cohort of 226 COVID-19 patients, critically ill individuals had higher collagen degradation (C3M, C6M) and synthesis (PRO-C3, PRO-C6) neo-epitopes than severely ill patients. Elevated and rising ECM turnover during ICU stay associated with mortality; dexamethasone attenuated increases in C6M and PRO-C6 yet did not translate into survival benefit.

Key Findings

• Critically ill patients showed higher collagen degradation (C3M, C6M) and synthesis (PRO-C3, PRO-C6) markers than severe cases.
• Increased ECM turnover during ICU stay was associated with mortality; non-survivors exhibited rising biomarkers over time.
• Dexamethasone attenuated increases in C6M and PRO-C6 in non-survivors, without a corresponding survival benefit.

Clinical Implications

ECM neo-epitope panels (e.g., C3M, C6M, PRO-C3, PRO-C6) may help prognosticate during ICU stay; corticosteroids may dampen matrix turnover but should not be expected to improve survival solely via this mechanism. Consider integrating serial biomarker monitoring into studies of antifibrotic or immunomodulatory therapies.

Limitations

• Observational design limits causal inference regarding dexamethasone effects
• Potential confounding by indication and treatment heterogeneity

Future Directions

Validate ECM neo-epitope panels for risk stratification across ARDS etiologies and test whether targeted antifibrotic/immunomodulatory strategies that reduce turnover improve patient-centered outcomes.