Mast cell activation may contribute to adverse health transitions in COVID-19 patients with frailty

A prominent aspect of the post-coronavirus disease-2019 (post-COVID-19) era is long-COVID. Therefore, precise patient classification and exploration of the corresponding factors affecting long-COVID are crucial for tailored treatment strategies. Frailty is a common age-related clinical syndrome characterized by deteriorated physiological functions of multiple organ systems, which increases susceptibility to stressors. Herein, we performed an inclusion and exclusion analysis (definite COVID-19 infection diagnosis, clear underlying disease information, ≥60 years old, and repeated sampling of clinical cases) of 10,613 blood samples and identified frailty cases for further investigation. RNA-Seq data were used for differential gene expression and functional and pathway analyses. The results revealed that patients with frailty were more prone to poor health conversions and more sequelae, and the blood transcriptome had obvious disturbances in pathways associated with immune regulation, metabolism, and stress response. These adverse health transitions were significantly associated with mast cell activation. Additionally, NCAPG, MCM10, and CDC25C were identified as hub genes in the peripheral blood differential gene cluster, which could be used as diagnostic markers of poor health conversion. Our results indicate that healthcare measures should be prioritized to mitigate adverse health outcomes in this vulnerable patient group, COVID-19 patients with frailty, in post-COVID era.

新型冠状病毒肺炎（Coronavirus Disease 2019，COVID-19）后疫情时代的显著特征之一为长新冠（long-COVID）。因此，对患者进行精准分类并探究影响长新冠的相关因素，对于制定个体化治疗策略至关重要。衰弱综合征是一类常见的年龄相关性临床综合征，以多器官系统生理功能衰退为特征，可增加机体对应激原的易感性。本研究针对10613份血液样本开展纳入排除标准分析（明确的COVID-19感染诊断、清晰的基础疾病信息、年龄≥60岁以及临床病例的重复采样），筛选出衰弱综合征病例以开展后续研究。本研究利用RNA测序（RNA-Seq）数据开展差异基因表达分析、功能分析及通路分析。研究结果显示，衰弱综合征患者更易出现不良健康转归及更多后遗症；其血液转录组在免疫调控、代谢与应激反应相关通路上存在显著紊乱。上述不良健康转归与肥大细胞活化显著相关。此外，本研究在外周血差异基因簇中鉴定出NCAPG、MCM10及CDC25C作为枢纽基因，这些基因可作为不良健康转归的诊断标志物。本研究结果提示，在后疫情时代，应优先落实医疗干预措施，以改善衰弱综合征新冠患者这一脆弱群体的不良健康结局。