背景:Omicron变体以其快速传染性影响人群,部分患者患有持续性症状,称为长COVID。这种目前主要的全球变异导致长期COVID的分子和免疫机制仍不清楚,由于人群之间长期的COVID异质性。
方法:我们总共招募了66名参与者,66人中有22人是健康对照,没有COVID-19感染史,22名抱怨首次感染Omicron后6个月出现长期COVID症状,称为长COVID(LC)组。左侧定义为非长型COVID(NLC)组。我们通过血浆中和抗体滴度对它们进行了分析,SARS-CoV-2病毒载量,转录组学和蛋白质组学筛选,和机器学习。
结果:在COVID-19感染后6个月,未观察到SARS-CoV-2的血清残留。长COVID(LC)组和非长COVID(NLC)组之间的中和抗体滴度没有显着差异。转录组学和蛋白质组学分析允许将长COVID分层为中性粒细胞功能上调(NU-LC)和下调(ND-LC)类型。NU-LC,通过一套完善的5种血液基因标记(ABCA13,CEACAM6,CRISP3,CTSG和BPI),在感染后6个月显示中性粒细胞计数和脱颗粒功能高于ND-LC的证据,在COVID-19后12个月康复。
结论:转录组和蛋白质组分析显示长型COVID患者之间存在异质性。我们发现了一个以中性粒细胞活化为特征的长COVID人群亚组,这可能与精神症状的发展有关,并表明较高的炎症状态。同时,人工筛选了一组5个基因,作为长COVID人群中NU-LC的最有效鉴别器。本研究可作为长型COVID发病机制异质性的基础探索,有助于长型COVID的治疗靶向和详细的流行病学调查。
BACKGROUND: Omicron variant impacts populations with its rapid contagiousness, and part of patients suffered from persistent symptoms termed as long COVID. The molecular and immune mechanisms of this currently dominant global variant leading to long COVID remain unclear, due to long COVID heterogeneity across populations.
METHODS: We recruited 66 participants in total, 22 out of 66 were healthy control without COVID-19 infection history, and 22 complaining about long COVID symptoms 6 months after first infection of Omicron, referred as long COVID (LC) Group. The left ones were defined as non-long COVID (NLC) Group. We profiled them via plasma neutralizing antibody titer, SARS-CoV-2 viral load, transcriptomic and proteomics screening, and machine learning.
RESULTS: No serum residual SARS-CoV-2 was observed in the participants 6 months post COVID-19 infection. No significant difference in neutralizing antibody titers was found between the long COVID (LC) Group and the non-long COVID (NLC) Group. Transcriptomic and proteomic profiling allow the stratification of long COVID into neutrophil function upregulated (NU-LC) and downregulated types (ND-LC). The NU-LC, identifiable through a refined set of 5 blood gene markers (ABCA13, CEACAM6, CRISP3, CTSG and BPI), displays evidence of relatively higher neutrophil counts and function of degranulation than the ND-LC at 6 months after infection, while recovered at 12 months post COVID-19.
CONCLUSIONS: The transcriptomic and proteomic profiling revealed heterogeneity among long COVID patients. We discovered a subgroup of long COVID population characterized by neutrophil activation, which might associate with the development of psychiatric symptoms and indicate a higher inflammatory state. Meanwhile, a cluster of 5 genes was manually curated as the most potent discriminators of NU-LC from long COVID population. This study can serve as a foundational exploration of the heterogeneity in the pathogenesis of long COVID and assist in therapeutic targeting and detailed epidemiological investigation of long COVID.