From pandemic onset to present: five years of insights into ARDS caused by COVID-19

COVID-19-associated acute respiratory distress syndrome (ARDS) has challenged healthcare systems, initially resembling classical ARDS but later recognized as distinct. Unique features such as endothelial injury, microthrombosis, and dysregulated inflammation influenced treatment efficacy. Understanding its evolution is key to optimizing therapy and improving outcomes.

This review synthesizes current evidence on COVID-19-associated ARDS, covering epidemiology, pathophysiology, clinical phenotypes, and treatments. It explores the shift from L and H phenotypes to a refined disease model and highlights key therapies, including corticosteroids, immunomodulators, prone positioning, ECMO, and vaccination's impact on severity and ARDS incidence.

At the onset of the COVID-19 pandemic in December 2019, uncertainty was overwhelming. Early clinical guidelines relied on case reports and small case series, offering only preliminary insights into disease progression and management. Despite the initial chaos, the scientific community launched an unprecedented research effort, with over 11,000 clinical trials registered on ClinicalTrials.gov investigating COVID-19 treatments. Several evidence-based strategies emerged as gold standards for managing COVID-19-associated acute respiratory distress syndrome, surpassing prior approaches. The pandemic exposed vulnerabilities in global healthcare, reshaped modern medicine, accelerated innovation, and reinforced the essential role of evidence-based practice in critical care and public health policy.