Journal Article

Endothelial dysfunction and persistent inflammation in severe post-COVID-19 patients: implications for gas exchange

López-Fernández, Cristina, Díaz-García, Elena, Añón, José M., Alfaro, Enrique, García-Tovar, Sara, Casitas, Raquel, Cubillos-Zapata, Carolina, García-Río, Francisco, Torres-Vargas, María, Galera, Raúl

2024

Overview

Background Understanding the enduring 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). Methods 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. Results 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, sCD40-L, and C-reactive protein, 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 interferon-β (IFN-β) further contributed to sustained inflammation. The in vitro model confirmed that patient plasma, with altered levels of sCD40-L and IFN-β proteins, has the capacity to alter endothelial function. Conclusions Six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibited 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, potentially intensified by sustained viral immune response.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acute respiratory distress syndrome / Adult / Aged / Analysis / Biological response modifiers / Biomarkers / Biomarkers - blood / Biomedicine / C-reactive protein / Care and treatment / CD69 antigen / Cell activation / Complications / COVID-19 / COVID-19 - blood / COVID-19 - complications / Cytokines / Development and progression / Dyspnea / Endothelial cells / Endothelial dysfunction / Endothelium / Endothelium, Vascular - physiopathology / Ethylenediaminetetraacetic acid / Evaluation / Female / Flow cytometry / Gas exchange / Health aspects / Human Umbilical Vein Endothelial Cells / Humans / ICAM-1 / Immune response / Inflammasomes / Inflammation / Intercellular adhesion molecule 1 / Interferon / Lymphocytes T / Male / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Middle Aged / NLR Family, Pyrin Domain-Containing 3 Protein / Patient outcomes / Patients / Physiology, Pathological / Plasma / Plasma levels / Post-COVID-19 syndrome / Proteins / Pulmonary Gas Exchange / Quality of life / Research Article / Respiratory distress syndrome / Respiratory Distress Syndrome - physiopathology / Respiratory Distress Syndrome - virology / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Software / T cells / Umbilical vein / Variables / β-Interferon