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重症和危重症新冠肺炎肺炎康复患者的长期肺部后遗症及免疫标志物:一项综合随访研究

Long-Term Pulmonary Sequelae and Immunological Markers in Patients Recovering from Severe and Critical COVID-19 Pneumonia: A Comprehensive Follow-Up Study.

作者信息

Strumiliene Edita, Urbonienė Jurgita, Jurgauskiene Laimute, Zeleckiene Ingrida, Bliudzius Rytis, Malinauskiene Laura, Zablockiene Birutė, Samuilis Arturas, Jancoriene Ligita

机构信息

Clinic of Infectious Diseases and Dermatovenerology, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 01513 Vilnius, Lithuania.

Centre of Infectious Diseases, Vilnius University Hospital Santaros klinikos, 08661 Vilnius, Lithuania.

出版信息

Medicina (Kaunas). 2024 Nov 27;60(12):1954. doi: 10.3390/medicina60121954.

DOI:10.3390/medicina60121954
PMID:39768836
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11678914/
Abstract

: Severe and critical COVID-19 pneumonia can lead to long-term complications, especially affecting pulmonary function and immune health. However, the extent and progression of these complications over time are not well understood. This study aimed to assess lung function, radiological changes, and some immune parameters in survivors of severe and critical COVID-19 up to 12 months after hospital discharge. : This prospective observational cohort study followed 85 adult patients who were hospitalized with severe or critical COVID-19 pneumonia at a tertiary care hospital in Vilnius, Lithuania, for 12 months post-discharge. Pulmonary function tests (PFTs), including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusion capacity for carbon monoxide (DLCO), were conducted at 3, 6, and 12 months. High-resolution chest computed tomography (CT) scans assessed residual inflammatory and profibrotic/fibrotic abnormalities. Lymphocyte subpopulations were evaluated via flow cytometry during follow-up visits to monitor immune status. : The median age of the cohort was 59 years (IQR: 51-64). Fifty-three (62.4%) patients had critical COVID-19 disease. Pulmonary function improved significantly over time, with increases in FVC, FEV1, VC, TLC, and DLCO. Residual volume (RV) did not change significantly over time, suggesting that some aspects of lung function, such as air trapping, remained stable and may require attention in follow-up care. The percentage of patients with restrictive spirometry patterns decreased from 24.71% at 3 months to 14.8% at 12 months ( < 0.05). Residual inflammatory changes on CT were present in 77.63% at 6 months, decreasing to 69.62% at 12 months ( < 0.001). Profibrotic changes remained prevalent, affecting 82.89% of patients at 6 months and 73.08% at 12 months. Lymphocyte counts declined significantly from 3 to 12 months (2077 cells/µL vs. 1845 cells/µL, = 0.034), with notable reductions in CD3+ ( = 0.040), CD8+ ( = 0.007), and activated CD3HLA-DR+ cells ( < 0.001). This study found that higher CD4+ T cell counts were associated with worse lung function, particularly reduced total lung capacity (TLC), while higher CD8+ T cell levels were linked to improved pulmonary outcomes, such as increased forced vital capacity (FVC) and vital capacity (VC). Multivariable regression analyses revealed that increased levels of CD4+/CD28+/CD192+ T cells were associated with worsening lung function, while higher CD8+/CD28+/CD192+ T cell counts were linked to better pulmonary outcomes, indicating that immune dysregulation plays a critical role in long-term respiratory recovery. : Survivors of severe and critical COVID-19 pneumonia continue to experience significant long-term impairments in lung function and immune system health. Regular monitoring of pulmonary function, radiological changes, and immune parameters is essential for guiding personalized post-COVID-19 care and improving long-term outcomes. Further research is needed to explore the mechanisms behind these complications and to develop targeted interventions for long COVID-19.

摘要

重症和危重症新型冠状病毒肺炎可导致长期并发症,尤其会影响肺功能和免疫健康。然而,这些并发症随时间的发展程度尚不清楚。本研究旨在评估重症和危重症新型冠状病毒肺炎幸存者出院后长达12个月的肺功能、影像学变化及一些免疫参数。

这项前瞻性观察性队列研究对85例成年患者进行了为期12个月的随访,这些患者在立陶宛维尔纽斯的一家三级护理医院因重症或危重症新型冠状病毒肺炎住院。在3个月、6个月和12个月时进行了肺功能测试(PFTs),包括用力肺活量(FVC)、1秒用力呼气量(FEV1)和一氧化碳弥散量(DLCO)。通过高分辨率胸部计算机断层扫描(CT)评估残留的炎症和纤维化/纤维化异常。在随访期间通过流式细胞术评估淋巴细胞亚群,以监测免疫状态。

该队列的中位年龄为59岁(四分位间距:51 - 64岁)。53例(62.4%)患者患有危重症新型冠状病毒肺炎。随着时间的推移,肺功能显著改善,FVC、FEV1、肺活量(VC)、肺总量(TLC)和DLCO均有所增加。残气量(RV)随时间无显著变化,这表明肺功能的某些方面,如气体潴留,保持稳定,在后续护理中可能需要关注。限制性肺量计模式患者的比例从3个月时的24.71%降至12个月时的14.8%(P<0.05)。CT上残留的炎症变化在6个月时为77.63%,在12个月时降至69.62%(P<0.001)。纤维化改变仍然普遍,6个月时影响82.89%的患者,12个月时影响73.08%的患者。淋巴细胞计数从3个月到12个月显著下降(2077个细胞/µL对1845个细胞/µL,P = 0.034),CD3 +(P = 0.040)、CD8 +(P = 0.007)和活化的CD3 HLA - DR +细胞显著减少(P<0.001)。本研究发现,较高的CD4 + T细胞计数与较差的肺功能相关,尤其是肺总量(TLC)降低,而较高的CD8 + T细胞水平与改善的肺部结局相关,如用力肺活量(FVC)和肺活量(VC)增加。多变量回归分析显示,CD4 + /CD28 + /CD192 + T细胞水平升高与肺功能恶化相关,而较高的CD8 + /CD28 + /CD192 + T细胞计数与更好的肺部结局相关,这表明免疫失调在长期呼吸恢复中起关键作用。

重症和危重症新型冠状病毒肺炎幸存者在肺功能和免疫系统健康方面仍持续存在显著的长期损害。定期监测肺功能、影像学变化和免疫参数对于指导新型冠状病毒肺炎后的个性化护理和改善长期结局至关重要。需要进一步研究以探索这些并发症背后的机制,并为长期新冠开发针对性干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ace/11678914/ca0aa97b7b12/medicina-60-01954-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ace/11678914/99f3a940a8e0/medicina-60-01954-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ace/11678914/de22a5de7b56/medicina-60-01954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ace/11678914/ca0aa97b7b12/medicina-60-01954-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ace/11678914/99f3a940a8e0/medicina-60-01954-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ace/11678914/de22a5de7b56/medicina-60-01954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ace/11678914/ca0aa97b7b12/medicina-60-01954-g003.jpg

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本文引用的文献

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