Endothelial Dysfunction and Persistent Inflammation in Severe Post-COVID-19 Patients: Implications for Gas Exchange

Understanding the respiratory consequences of severe COVID-19 is crucial for comprehensive patient care. This study aims to evaluate the impact of post-COVID conditions on respiratory sequelae of severe acute respiratory distress syndrome (ARDS). We examined 88 survivors of COVID-19-associated severe ARDS six months post-intensive care unit (ICU) discharge. Assessments included clinical and functional evaluation as well as plasma biomarkers of endothelial dysfunction, inflammation, and viral response. Additionally, an in vitro model using human umbilical vein endothelial cells (HUVECs) explored the direct impact of post-COVID plasma on endothelial function. Post-COVID patients with impaired gas exchange demonstrated persistent endothelial inflammation marked by elevated ICAM-1, IL-8, CCL-2, and ET-1 plasma levels. Concurrently, systemic inflammation, evidenced by NLRP3 overexpression and elevated levels of IL-6, TNF-α, and sCD40L, was associated with endothelial dysfunction biomarkers and increased in post-COVID patients with impaired gas exchange. T-cell activation, reflected in CD69 expression, and persistently elevated levels of IFN‑β further contributed to sustained inflammation. The in vitro model confirmed that patients’ plasma, with increased levels of sCD40-L and IFN-β proteins, alters endothelial function. In conclusion, six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibit sustained elevation in endothelial dysfunction biomarkers, correlating with the severity of impaired gas exchange. NLRP3 inflammasome activity and persistent T-cell activation indicate on going inflammation contributing to persistent endothelial dysfunction.