Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Shanghai Sci-Tech Inno Center for Infection & Immunity, Shanghai, China.
J Transl Med. 2024 Aug 12;22(1):753. doi: 10.1186/s12967-024-05560-6.
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.
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.
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.
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.
奥密克戎变异株具有快速传染性，部分患者出现了被称为长新冠的持续症状。由于长新冠在不同人群中的异质性，导致目前这种主要的全球变异株导致长新冠的分子和免疫机制仍不清楚。
我们总共招募了 66 名参与者，其中 22 名来自无新冠感染史的健康对照组，22 名患有奥密克戎感染后 6 个月出现长新冠症状，称为长新冠（LC）组。其余的被定义为非长新冠（NLC）组。我们通过血浆中和抗体滴度、SARS-CoV-2 病毒载量、转录组和蛋白质组筛选以及机器学习对他们进行了分析。
在新冠感染后 6 个月，参与者的血清中未检测到残留的 SARS-CoV-2。长新冠（LC）组和非长新冠（NLC）组之间的中和抗体滴度无显著差异。转录组和蛋白质组分析可将长新冠分为中性粒细胞功能上调（NU-LC）和下调类型（ND-LC）。NU-LC 通过一组 5 个血液基因标志物（ABCA13、CEACAM6、CRISP3、CTSG 和 BPI）来识别，在感染后 6 个月时表现出相对较高的中性粒细胞计数和脱颗粒功能，而在新冠感染后 12 个月时恢复正常。
转录组和蛋白质组分析揭示了长新冠患者之间的异质性。我们发现了一个长新冠人群的亚组，其特征是中性粒细胞激活，这可能与精神症状的发展有关，并表明存在更高的炎症状态。同时，一组 5 个基因被手工筛选为 NU-LC 与长新冠人群最有效的鉴别标志物。这项研究可以作为长新冠发病机制异质性的基础探索，有助于治疗靶点的确定和长新冠的详细流行病学调查。
