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持续高Myl9水平与急性后新冠综合征的发病机制及呼吸道症状相关:一项6个月的随访研究。

Prolonged high Myl9 levels are associated with the pathogenesis and respiratory symptom of post-acute COVID-19 syndrome: A 6-month follow-up study.

作者信息

Sugihara Jun, Iwamura Chiaki, Tateishi Tomoya, Hosoya Tadashi, Shimada Sho, Hirahara Kiyoshi, Yasuda Shinsuke, Miyazaki Yasunari

机构信息

Department of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.

Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.

出版信息

Clinics (Sao Paulo). 2025 Jan 28;80:100584. doi: 10.1016/j.clinsp.2025.100584. eCollection 2025.

Abstract

BACKGROUND

Post-acute COVID-19 Syndrome (PACS) occurs in some COVID-19 patients long after acute infection and significantly affects patients' health. However, the mechanism by which PACS develops is unknown. Myosin light chain 9 (Myl9), produced by activated platelets, plays a role in immune dysregulation and microthrombi formation during acute COVID-19. However, in the PACS phase, the association between Myl9 and residual symptoms remains unclear, and further investigation is needed.

METHODS

In this prospective cohort study, serum Myl9 concentrations were measured in 195 COVID-19 patients during hospitalization and at 3- and 6-month follow-up visits. Gaussian mixture modeling was used to identify groups on the basis of Myl9 levels. Relationships between Myl9 levels and residual symptoms were evaluated. Clinical characteristics influencing Myl9 levels were analyzed via logistic regression.

RESULTS

A total of 304 serum samples from 195 patients were collected. Two distinct groups were identified in the Myl9 distribution with a cutoff of 386 ng/mL by Gaussian mixture modeling in this cohort. The high-Myl9 group presented significant residual respiratory symptoms at 6 months post-infection (p < 0.05). Elevated Myl9 levels at 6 months were correlated with increased neutrophil counts (p < 0.01) and respiratory comorbidities at diagnosis (p < 0.05) according to univariate regression analysis. Multivariate regression analysis confirmed the relationship between the neutrophil count and high Myl9 levels.

CONCLUSION

Prolonged high Myl9 levels are associated with respiratory symptoms, suggesting the potential involvement of prolonged inflammation or endothelial damage in PACS.

摘要

背景

急性 COVID-19 后综合征(PACS)在一些 COVID-19 患者急性感染很久之后出现,并显著影响患者健康。然而,PACS 的发病机制尚不清楚。活化血小板产生的肌球蛋白轻链 9(Myl9)在急性 COVID-19 期间的免疫失调和微血栓形成中起作用。然而,在 PACS 阶段,Myl9 与残留症状之间的关联仍不清楚,需要进一步研究。

方法

在这项前瞻性队列研究中,对 195 名 COVID-19 患者在住院期间以及 3 个月和 6 个月随访时的血清 Myl9 浓度进行了测量。采用高斯混合模型根据 Myl9 水平识别分组。评估了 Myl9 水平与残留症状之间的关系。通过逻辑回归分析影响 Myl9 水平的临床特征。

结果

共收集了 195 名患者的 304 份血清样本。通过该队列中的高斯混合模型,在 Myl9 分布中确定了两个不同的组,临界值为 386 ng/mL。高 Myl9 组在感染后 6 个月出现明显的残留呼吸道症状(p < 0.05)。根据单变量回归分析,6 个月时 Myl9 水平升高与中性粒细胞计数增加(p < 0.01)和诊断时的呼吸道合并症(p < 0.05)相关。多变量回归分析证实了中性粒细胞计数与高 Myl9 水平之间的关系。

结论

Myl9 水平长期升高与呼吸道症状相关,提示 PACS 中可能存在长期炎症或内皮损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bc7/11814511/ea39c7bf4dac/gr1.jpg

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