Siekacz Kamil, Kumor-Kisielewska Anna, Miłkowska-Dymanowska Joanna, Pietrusińska Małgorzata, Bartczak Krystian, Majewski Sebastian, Stańczyk Adam, Piotrowski Wojciech J, Białas Adam J
Department of Pneumology, Medical University of Lodz, 90-419 Lodz, Poland.
Department of Clinical Pharmacology, Medical University of Lodz, 90-419 Lodz, Poland.
J Clin Med. 2023 Jun 25;12(13):4253. doi: 10.3390/jcm12134253.
The role of mitochondria in post coronavirus disease 2019 (post-COVID-19) complications is unclear, especially in the long-term pulmonary complications. This study aims to investigate the association between post-COVID-19 pulmonary complications and mitochondrial regulatory proteins in the context of oxidative stress.
Patients who had recovered from COVID-19 were enrolled. According to the evidence of persistent interstitial lung lesions on computed tomography (CT), patients were divided into a long-term pulmonary complications group (P(+)) and a control group without long-term pulmonary complications (P(-)). We randomly selected 80 patients for investigation (40 subjects for each group). Biomarkers levels were determined by enzyme-linked immunosorbent assay (ELISA).
The serum concentrations of mitochondrial regulatory proteins were significantly higher in the P(+) group, including PTEN-induced kinase 1 (PINK1): 1.62 [1.02-2.29] ng/mL vs. 1.34 [0.94-1.74] ng/mL ( = 0.046); Dynamin-1-like protein (DNM1L): 1.6 [0.9-2.4] ng/mL IQR vs. 0.9 [0.5-1.6] ng/mL ( = 0.004); and Mitofusin-2 (MFN2): 0.3 [0.2-0.5] ng/mL vs. 0.2 [0.1-0.3] ng/mL IQR ( = 0.001). Patients from the P(+) group also had higher serum levels of chemokine ligand 18 (PARC, CCL18), IL-6, and tumour necrosis factor-alpha (TNF-α) cytokines than the P(-) group. The concentration of interferon alpha (IFN-α) was decreased in the P(+) group. Furthermore, we observed statistically significant correlations between the advanced glycation end product (sRAGE) and TNF-α (Pearson's factor R = 0.637; < 0.001) and between serum levels of DNM1L and IFN-α (Pearson's factor R = 0.501; = 0.002) in P(+) patients.
Elevated concentrations of mitochondrial biomarkers in post-COVID-19 patients with long-term pulmonary complications indicate their possible role in the pathobiology of COVID-19 pulmonary sequelae. Oxidative stress is associated with the immune response and inflammation after COVID-19. TNF-α could be a promising biomarker for predicting pulmonary complications and may be a potential target for therapeutic intervention in patients with post-COVID-19 complications.
线粒体在2019冠状病毒病后（COVID-19后）并发症中的作用尚不清楚，尤其是在长期肺部并发症方面。本研究旨在探讨COVID-19后肺部并发症与氧化应激背景下线粒体调节蛋白之间的关联。
纳入从COVID-19中康复的患者。根据计算机断层扫描（CT）上持续性间质性肺病变的证据，将患者分为长期肺部并发症组（P(+)）和无长期肺部并发症的对照组（P(-)）。我们随机选择80例患者进行调查（每组40例受试者）。通过酶联免疫吸附测定（ELISA）测定生物标志物水平。
P(+)组线粒体调节蛋白的血清浓度显著更高，包括PTEN诱导激酶1（PINK1）：1.62 [1.02 - 2.29] ng/mL 对比 1.34 [0.94 - 1.74] ng/mL（P = 0.046）；动力蛋白样蛋白1（DNM1L）：1.6 [0.9 - 2.4] ng/mL（四分位间距）对比0.9 [0.5 - 1.6] ng/mL（P = 0.004）；以及线粒体融合蛋白2（MFN2）：0.3 [0.2 - 0.5] ng/mL对比0.2 [0.1 - 0.3] ng/mL（四分位间距）（P = 0.001）。P(+)组患者的趋化因子配体18（PARC，CCL18）、IL-6和肿瘤坏死因子-α（TNF-α）细胞因子的血清水平也高于P(-)组。P(+)组中干扰素α（IFN-α）的浓度降低。此外，我们在P(+)患者中观察到晚期糖基化终末产物（sRAGE）与TNF-α之间（Pearson因子R = 0.637；P < 0.001）以及DNM1L血清水平与IFN-α之间（Pearson因子R = 0.501；P = 0.002）存在统计学显著相关性。
COVID-19后有长期肺部并发症患者中线粒体生物标志物浓度升高表明它们可能在COVID-19肺部后遗症的病理生物学中起作用。氧化应激与COVID-19后的免疫反应和炎症相关。TNF-α可能是预测肺部并发症的有前景的生物标志物，并且可能是COVID-19后并发症患者治疗干预的潜在靶点。
