PDF(Pubmed)
Abstract：
Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the pathobiological mechanisms are multifactorial. By analyzing early virally infected upper respiratory tract tissue prior to eventual clinical diagnosis, it may be possible to identify biomarkers of altered immune response to facilitate future studies and interventions. Methods: This is a sub-group analysis of samples collected from those with confirmed COVID-19. RNA extraction from nasopharyngeal/mid-turbinate samples, sequencing, and bioinformatic analysis were performed to analyze long COVID and non-long COVID cohorts at day 14 post infection. Differences in mean viral load at various timepoints were analyzed as well as serological data. Results: We identified 26 upregulated genes in patients experiencing long COVID. Dysregulated pathways including complement and fibrinolysis pathways and IL-7 upregulation. Additionally, genes involved in neurotransmission were dysregulated, and the long COVID group had a significantly higher viral load and slower viral clearance. Conclusions: Uncovering early gene pathway abnormalities associated with eventual long COVID diagnosis may aid in early identification. We show that, post acute infection, in situ pathogenic deviations in viral response are associated with patients destined to meet consensus long COVID diagnosis that is entirely dependent on clinical factors. These results identify an important biological temporal window in the natural history of COVID-19 infection and long COVID pathogenesis amenable to testing from standard-of-care upper respiratory tract specimens.
摘要：
背景：COVID-19或长COVID急性后遗症，是一种以持续的COVID-19症状为特征的疾病。只要COVID在经过一段时间后由临床标准定义，早期干预的机会可能有助于未来的预防方法；然而，目前,病理生物学机制是多因素的。通过在最终临床诊断之前分析早期病毒感染的上呼吸道组织，有可能鉴定免疫应答改变的生物标志物,以促进未来的研究和干预.方法：这是从确诊的COVID-19患者中收集的样本的亚组分析。从鼻咽/中鼻甲样品中提取RNA，测序,测序并在感染后第14天进行生物信息学分析，以分析长COVID和非长COVID队列。分析了不同时间点平均病毒载量的差异以及血清学数据。结果：我们在长期COVID患者中鉴定出26个上调基因。失调途径包括补体和纤维蛋白溶解途径和IL-7上调。此外,参与神经传递的基因失调，而长COVID组的病毒载量明显更高，病毒清除率更慢。结论：发现与最终长期COVID诊断相关的早期基因通路异常可能有助于早期识别。我们证明,急性感染后，病毒应答的原位致病差异与注定要达到COVID长期一致诊断的患者相关,而这完全取决于临床因素.这些结果在COVID-19感染的自然史中确定了一个重要的生物学时间窗，并且长期的COVID发病机理可以从护理标准的上呼吸道标本中进行检测。
