长期免疫激活在SARS-CoV-2的后急性后续:中性粒细胞动态和治疗见解
Mina Yu1,2, Suhee Hwang1,3, Hobin Jang1
1Center for Study of Emerging and Re-emerging Viruses, Korea Virus Research Institute, Institute for Basic Science, Daejeon, Republic of Korea.
Experimental & molecular medicine
|September 23, 2025
概括
SARS-CoV-2 (PASC) 后急性后续包括持续的症状. 中性粒细胞激活在PASC中驱动肺损伤,但像Sivelestat这样的抑制剂显示出治疗前景.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 病理学 病理学 病理学
背景情况:
- SARS-CoV-2 (PASC) 后急性后续 presents显著的长期健康挑战,包括疲劳和认知功能障碍.
- 帕斯克的潜在机制在很大程度上是未知的,这阻碍了有效的治疗开发.
- 了解PASC病原体对于管理COVID-19幸存者的持续症状至关重要.
研究的目的:
- 为了研究SARS-CoV-2感染的长期影响,并使用仓鼠模型将其与流感A病毒进行比较.
- 确定推动PASC的细胞和分子机制.
- 评估针对中性粒细胞介导炎症的潜在治疗策略.
主要方法:
- 在SARS-CoV-2和流感A病毒感染研究中使用了Phodopus roborovskii仓鼠模型.
- 在感染后30天,在支气管洗液,肺和脏样本上使用单细胞RNA测序.
- 进行了免疫组织化学,并评估了小分子抑制剂的疗效,包括Sivelestat.
主要成果:
- 一组SARS-CoV-2幸存者发展了PASC,其特点是体重恢复受损,肺病理和中性粒细胞积累.
- 单细胞RNA测序揭示了 PASC 仓鼠中独特的 PASC 基因特征,高中性粒细胞和减少的巨细胞.
- 在PASC肺部观察到持续的SARS-CoV-2 S1抗原和中性粒细胞透,与与炎症相关的基因上调相关.
- 用抑制剂向中性粒细胞介导炎症,特别是西维莱斯塔特,显著降低了PASC表型,发病率和死亡率.
结论:
- 中性粒细胞激活在PASC中驱动肺损伤和慢性炎症方面发挥着关键作用.
- 持久的SARS-CoV-2抗原可能有助于持续的中性粒细胞招募和激活.
- 中性粒细胞弹性酶抑制是一种有前途的治疗策略,可以缓解PASC.
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