Clinical therapeutics · 2025
Experimental Evidence of Dexamethasone in Reversing Endothelial Dysfunction in COVID-19: Therapeutic Insights from Intranasal Administration.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Trejo-Moreno Celeste, Méndez-Martínez Marisol, Alvarado-Ojeda Zimri A, Sifontes-Rodríguez Sergio, Cervantes-Torres Jaquelynne, Bobes Raul J, Laclette Juan P, Sciutto Edda, Fragoso Gladis, Rosas-Salgado Gabriela
Аннотация
PURPOSE: Vascular endothelial dysfunction (ED) plays a critical role in the pathogenesis of severe COVID-19. Intranasal dexamethasone (IN-DXM) has been reported to improve clinical outcomes more efficiently than intravenous (IV-DXM) administration in hospitalized patients. This study compared the efficacy of both regimens in improving ED.
METHODS: Hospitalized COVID-19 patients from the REVIVAL trial received either intranasal dexamethasone (IN-DXM) via a MAD-Nasal device (0.12 mg/kg for 3 days followed by 0.06 mg/kg for 7 days; n = 10) or intravenous dexamethasone (IV-DXM; 6 mg/day for 10 days; n = 7). Respiratory and inflammatory parameters were analyzed before and 10 days after treatment. Serum levels of IL-6, malondialdehyde (MDA), and nitric oxide (NO) metabolites (nitrites) were quantified, along with their effects on human microvascular endothelial cells (HMEC-1) incubated with patient or control sera.
FINDINGS: COVID-19 infection significantly increased IL-6 and MDA and reduced NO levels. Only IN-DXM significantly improved respiratory parameters (FiO₂, SatO₂, pO₂) and reduced serum IL-6. Both regimens decreased peripheral inflammatory markers (C-reactive protein, neutrophil-to-lymphocyte ratio and fibrinogen) and increased NO approaching control levels, improving the vascular function. Notably, only sera from IN-DXM-treated patients normalized IL-6 levels in HMEC-1 supernatants to those of controls. Regardless of the administration route, supernatants from HMEC-1 cells incubated with sera from treated patients showed decreased MDA and increased NO compared with those obtained before treatment.
IMPLICATIONS: The IN-DXM regimen produced greater improvement in respiratory and inflammatory parameters than IV-DXM, supporting its potential as a practical and effective alternative for managing severe COVID-19-associated endothelial dysfunction.
METHODS: Hospitalized COVID-19 patients from the REVIVAL trial received either intranasal dexamethasone (IN-DXM) via a MAD-Nasal device (0.12 mg/kg for 3 days followed by 0.06 mg/kg for 7 days; n = 10) or intravenous dexamethasone (IV-DXM; 6 mg/day for 10 days; n = 7). Respiratory and inflammatory parameters were analyzed before and 10 days after treatment. Serum levels of IL-6, malondialdehyde (MDA), and nitric oxide (NO) metabolites (nitrites) were quantified, along with their effects on human microvascular endothelial cells (HMEC-1) incubated with patient or control sera.
FINDINGS: COVID-19 infection significantly increased IL-6 and MDA and reduced NO levels. Only IN-DXM significantly improved respiratory parameters (FiO₂, SatO₂, pO₂) and reduced serum IL-6. Both regimens decreased peripheral inflammatory markers (C-reactive protein, neutrophil-to-lymphocyte ratio and fibrinogen) and increased NO approaching control levels, improving the vascular function. Notably, only sera from IN-DXM-treated patients normalized IL-6 levels in HMEC-1 supernatants to those of controls. Regardless of the administration route, supernatants from HMEC-1 cells incubated with sera from treated patients showed decreased MDA and increased NO compared with those obtained before treatment.
IMPLICATIONS: The IN-DXM regimen produced greater improvement in respiratory and inflammatory parameters than IV-DXM, supporting its potential as a practical and effective alternative for managing severe COVID-19-associated endothelial dysfunction.