Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.
Cell Biochem Funct. 2022 Oct;40(7):694-705. doi: 10.1002/cbf.3735. Epub 2022 Aug 18.
The aim of this study was to evaluate the systemic redox state and inflammatory markers in intensive care unit (ICU) or non-ICU severe COVID-19 patients during the hospitalization period. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients), 5-7 days after admission (T2: 5-7 days after hospital admission), and at the discharge time from the hospital (T3: 0-72 h before leaving hospital or death) to analyze systemic oxidative stress markers and inflammatory variables. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were analyzed in peripheral granulocytes and monocytes. THP-1 human monocytic cell line was incubated with plasma from non-ICU and ICU COVID-19 patients and cell viability and apoptosis rate were analyzed. Higher total antioxidant capacity, protein oxidation, lipid peroxidation, and IL-6 at hospital admission were identified in both non-ICU and ICU COVID-19 patients. ICU COVID-19 patients presented increased C-reactive protein, ROS levels, and protein oxidation over hospitalization period compared to non-ICU patients, despite increased antioxidant status. Granulocytes and monocytes of non-ICU and ICU COVID-19 patients presented lower MMP and higher ROS production compared to the healthy controls, with the highest values found in ICU COVID-19 group. Finally, the incubation of THP-1 cells with plasma acquired from ICU COVID-19 patients at T3 hospitalization period decreased cell viability and apoptosis rate. In conclusion, disturbance in redox state is a hallmark of severe COVID-19 and is associated with cell damage and death.
本研究旨在评估住院期间 ICU 和非 ICU 重症 COVID-19 患者的全身氧化还原状态和炎症标志物。在入院时(T1)(对照组和 COVID-19 患者)、入院后 5-7 天(T2:入院后 5-7 天)和出院时(T3:离开医院或死亡前 0-72 小时)采集血样,以分析全身氧化应激标志物和炎症变量。在外周粒细胞和单核细胞中分析活性氧(ROS)产生和线粒体膜电位(MMP)。用非 ICU 和 ICU COVID-19 患者的血浆孵育 THP-1 人单核细胞系,并分析细胞活力和细胞凋亡率。入院时,非 ICU 和 ICU COVID-19 患者的总抗氧化能力、蛋白质氧化、脂质过氧化和 IL-6 均升高。与非 ICU 患者相比,ICU COVID-19 患者在整个住院期间的 CRP、ROS 水平和蛋白质氧化均升高,但抗氧化状态增加。与健康对照组相比,非 ICU 和 ICU COVID-19 患者的粒细胞和单核细胞的 MMP 较低,ROS 产生较高,其中 ICU COVID-19 组的数值最高。最后,用 ICU COVID-19 患者在 T3 住院期间获得的血浆孵育 THP-1 细胞,降低了细胞活力和细胞凋亡率。总之,氧化还原状态的紊乱是严重 COVID-19 的标志,并与细胞损伤和死亡有关。