Alfaro Enrique, Díaz-García Elena, García-Tovar Sara, Galera Raúl, Casitas Raquel, Torres-Vargas María, López-Fernández Cristina, Añón José M, García-Río Francisco, Cubillos-Zapata Carolina
Respiratory Diseases Group, Respiratory Service, La Paz University Hospital, IdiPAZ, Paseo de La Castellana 261, 28046, Madrid, Spain.
Biomedical Research Networking Centre On Respiratory Diseases (CIBERES), Madrid, Spain.
BMC Med. 2024 Jun 13;22(1):242. doi: 10.1186/s12916-024-03461-5.
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).
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, 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.
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.
了解重症新型冠状病毒肺炎（COVID-19）的长期呼吸后果对于全面的患者护理至关重要。本研究旨在评估COVID后状况对重症急性呼吸窘迫综合征（ARDS）呼吸后遗症的影响。
我们检查了88名COVID-19相关重症ARDS幸存者，这些患者在重症监护病房（ICU）出院后6个月。评估包括临床和功能评估以及内皮功能障碍、炎症和病毒反应的血浆生物标志物。此外，使用人脐静脉内皮细胞（HUVECs）的体外模型探讨了COVID后血浆对内皮功能的直接影响。
气体交换受损的COVID后患者表现出持续的内皮炎症，其特征是细胞间黏附分子-1（ICAM-1）、白细胞介素-8（IL-8）、趋化因子配体2（CCL-2）和内皮素-1（ET-1）血浆水平升高。同时，以NLRP3过表达以及IL-6、可溶性CD40配体（sCD40-L）和C反应蛋白水平升高为证据的全身炎症与内皮功能障碍生物标志物相关，并且在气体交换受损的COVID后患者中增加。CD69表达反映的T细胞活化以及干扰素-β（IFN-β）水平持续升高进一步导致持续炎症。体外模型证实，sCD40-L和IFN-β蛋白水平改变的患者血浆有能力改变内皮功能。
在ICU出院6个月后，COVID-19相关ARDS幸存者的内皮功能障碍生物标志物持续升高，与气体交换受损的严重程度相关。NLRP3炎性小体活性和持续的T细胞活化表明持续的炎症导致持续的内皮功能障碍，可能因持续的病毒免疫反应而加剧。
