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新型冠状病毒肺炎(COVID-19)急性感染患者呼吸肌的组织病理学分析

Histopathological analysis of respiratory muscles in patients with acute COVID-19 infection.

作者信息

Steingruber Laura, Handtke Simona, Schweiger Franziska, Schiele Stefan, Märkl Bruno, Koch Marco

机构信息

Anatomy and Cell Biology, Institute of Theoretical Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany.

Centre for Interdisciplinary Health Research (CIHR), University of Augsburg, Augsburg, Germany.

出版信息

Cell Tissue Res. 2025 May 5. doi: 10.1007/s00441-025-03973-3.

DOI:10.1007/s00441-025-03973-3
PMID:40323407
Abstract

Coronavirus-disease 2019 (COVID-19) affects the respiratory system with high morbidity in elderly and comorbid patients. Acute COVID-19 infection (CI) primarily leads to respiratory failure, long-term effects on respiratory skeletal muscle however remain vague. Thus, histopathological marker expression of oxidative stress, inflammation, satellite cell activity, myosin fiber composition, and cellular senescence were analyzed in intercostal muscle and diaphragm to compare respiratory muscle degeneration (RMD) in deceased CI-positive and control patients. Beside CI, the impact of BMI, age, sex, ventilation status, and duration of hospitalization on RMD were evaluated. CI-positive patients exhibited higher numbers of regenerative stem cells, but no association between CI status and RMD was observed. Interestingly, ventilation support and lung-associated comorbidities had no effect on expression of RMD markers (p > 0.05). However, intercostal muscle showed BMI-dependent changes in expression of RMD markers, regardless of the CI status, with increased cytokine expression (p = 0.04), reduced antioxidative capacity (p = 0.05), and low stem cell prevalence (p = 0.02) in patients with high BMI. Moreover, elderly patients demonstrated increased oxidative stress (p = 0.001) and cell senescence (p = 0.03) independent of CI status. Notably, immobility drives muscle fiber transformation to Myosin ST (p = 0.03), since prolonged hospitalization correlated with muscle fiber type shift. Limitations included incomplete retrospective data collection and absence of adequate samples for molecular analyses. Together, RMD is influenced by BMI, age and immobility rather than the CI status alone. Future studies including larger cohorts, molecular analyses, and evaluation of patient data in addition to CI status alone, will further support meaningful analyses and interpretation of RMD and its impact on post CI recovery.

摘要

2019冠状病毒病(COVID-19)对呼吸系统有影响,在老年人和合并症患者中发病率较高。急性COVID-19感染(CI)主要导致呼吸衰竭,然而其对呼吸骨骼肌的长期影响仍不明确。因此,分析了肋间肌和膈肌中氧化应激、炎症、卫星细胞活性、肌球蛋白纤维组成和细胞衰老的组织病理学标志物表达,以比较已故CI阳性患者和对照患者的呼吸肌退变(RMD)情况。除CI外,还评估了体重指数(BMI)、年龄、性别、通气状态和住院时间对RMD的影响。CI阳性患者的再生干细胞数量较多,但未观察到CI状态与RMD之间存在关联。有趣的是,通气支持和肺部相关合并症对RMD标志物的表达没有影响(p>0.05)。然而,无论CI状态如何,肋间肌均显示出RMD标志物表达的BMI依赖性变化,BMI较高的患者细胞因子表达增加(p=0.04)、抗氧化能力降低(p=0.05)且干细胞患病率较低(p=0.02)。此外,老年患者无论CI状态如何,均表现出氧化应激增加(p=0.001)和细胞衰老增加(p=0.03)。值得注意的是,不动会促使肌纤维转变为肌球蛋白ST(p=0.03),因为住院时间延长与肌纤维类型转变相关。局限性包括回顾性数据收集不完整以及缺乏用于分子分析的足够样本。总之,RMD受BMI、年龄和不动的影响,而非仅受CI状态影响。未来的研究包括更大的队列、分子分析以及除单独的CI状态外对患者数据的评估,将进一步支持对RMD及其对CI后恢复影响的有意义分析和解读。

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Histopathology of COVID-19: An illustration of the findings from fatal cases.新型冠状病毒肺炎的组织病理学:致命病例的研究结果图示
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