Visconti Nina R G, Rocha Nazareth N, Nascimento Gabriela S, Menário Caio V B, Silva Johnatas D, Martins Camila M, Caruso-Neves Celso, Cruz Fernanda F, Rocco Patricia R M, Mello Fernanda C Q, Lapa-E-Silva José R
Thoracic Disease Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Front Med (Lausanne). 2025 May 19;12:1547886. doi: 10.3389/fmed.2025.1547886. eCollection 2025.
Persistent fatigue is one of the most common and debilitating symptoms experienced by patients recovering from COVID-19, contributing significantly to the burden of "long COVID" or post-COVID-19syndrome. However, the underlying pathophysiological mechanisms remain inadequately understood. Few studies have examined the association between fatigue and pulmonary or cardiac function, systemic biomarkers, or morphological changes in the lungs and diaphragm. Furthermore, the potential influence of vaccination on the persistence of fatigue has not been fully explored. This study aims to identify mechanisms contributing to post-COVID-19 fatigue.
This prospective cohort study assessed clinical, laboratory, pulmonary, and cardiac parameters, as well as diaphragm ultrasound and pulmonary function, in patients with and without fatigue at least 4 months after discharge from hospitalization due to COVID-19.
Of 88 patients evaluated, 34% reported new or worsening fatigue after recovering from COVID-19. Demographic characteristics, comorbidities, and vaccination status were similar between fatigued and non-fatigued groups. However, ICU admission during the acute phase of illness emerged as a significant risk factor for fatigue (OR 2.65; 95% CI, 1.03-6.94) in multivariable analysis. No significant differences were observed in lung function, diaphragm or lung ultrasound findings, or left ventricular systolic function between groups. Fatigue was associated with significantly elevated serum levels of myostatin and irisin, markers of muscle metabolism. Additionally, patients experiencing fatigue reported poorer functional capacity and significantly reduced quality of life, with lower scores in multiple domains of the SF-36 questionnaire, including general health, vitality, and mental health.
Post-COVID-19 fatigue is strongly associated with prior ICU admission and elevated levels of myostatin and irisin, implicating potential myopathic mechanisms in its persistence. The profound impact of fatigue on functional capacity and quality of life highlights the urgent need for further research to elucidate its pathophysiology and develop targeted therapeutic strategies. This study provides critical insights into the interplay between systemic and organ-specific factors contributing to fatigue, offering a foundation for future interventions to improve outcomes in patients with long COVID.
持续性疲劳是新冠病毒感染康复患者最常见且使人衰弱的症状之一，是“长新冠”或新冠后综合征负担的重要因素。然而，其潜在的病理生理机制仍未得到充分了解。很少有研究探讨疲劳与肺或心脏功能、全身生物标志物，或肺和膈肌形态变化之间的关联。此外，疫苗接种对疲劳持续存在的潜在影响尚未得到充分研究。本研究旨在确定导致新冠后疲劳的机制。
这项前瞻性队列研究评估了因新冠病毒感染住院出院至少4个月后出现和未出现疲劳的患者的临床、实验室、肺和心脏参数，以及膈肌超声和肺功能。
在评估的88例患者中，34%报告称新冠康复后出现新的或加重的疲劳。疲劳组和非疲劳组的人口统计学特征、合并症和疫苗接种状况相似。然而，在多变量分析中，急性期入住重症监护病房（ICU）成为疲劳的一个重要危险因素（比值比2.65；95%置信区间，1.03 - 6.94）。两组之间在肺功能、膈肌或肺部超声检查结果，或左心室收缩功能方面未观察到显著差异。疲劳与血清中肌肉生长抑制素和鸢尾素水平显著升高有关，这两种物质是肌肉代谢的标志物。此外，出现疲劳的患者报告功能能力较差，生活质量显著降低，在SF - 36问卷的多个领域得分较低，包括总体健康、活力和心理健康。
新冠后疲劳与之前入住ICU以及肌肉生长抑制素和鸢尾素水平升高密切相关，提示其持续存在可能存在潜在的肌病机制。疲劳对功能能力和生活质量的深远影响凸显了进一步研究以阐明其病理生理学并制定针对性治疗策略的迫切需求。本研究为导致疲劳的全身因素和器官特异性因素之间的相互作用提供了关键见解，为未来改善长新冠患者预后的干预措施奠定了基础。
