Integrated miRNAome-transcriptome analyses identify an immuno-hematopoietic subcluster in patients with long COVID

IF 11.7 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology Pub Date : 2026-10-01 Epub Date: 2026-06-23 DOI:10.1016/j.jaci.2026.05.032

Ying Yang PhD, Mari Kanerva MD, PhD, Helena Liira MD, PhD, Aki Vuokko MD, PhD, Sini Laakso MD, PhD, Velina Vangelova-Korpinen MD, Shuyuan Wang PhD, Kirsi Kvarnström PhD, Mikko Varonen PhD, Hille Suojalehto MD, PhD, Antti Lauerma MD, PhD, Piia Karisola PhD, Harri Alenius PhD

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引用次数: 0

Abstract

Background

Persistent symptoms following SARS-CoV-2 infection, termed post-COVID-19 condition or long COVID (LC), impose substantial psychological and socioeconomic burdens. However, microRNA (miRNA)-mRNA interactions underlying LC heterogeneity remain incompletely defined.

Objective

We sought to determine whether integrative blood miRNA-mRNA profiling identifies molecular LC subclusters linked to clinical and immuno-hematopoietic features.

Methods

We performed integrated miRNAome-transcriptome profiling of circulating blood RNA from individuals with LC and recovered control participants. Differential miRNA and mRNA expression was assessed using limma software, and hierarchical clustering was used to define LC subclusters. Validated miRNA-mRNA interaction networks were constructed using the miRNet tool. Clinical, functional, and biochemical parameters were compared between subclusters, and a random forest classifier was developed.

Results

Clustering identified an immuno-hematopoietic LC subcluster, LC1, characterized by extensive miRNA-mRNA dysregulation; enrichment of erythropoietic, platelet, and immune pathways; and biochemical alterations including lower plasma sodium and elevated fibrin D-dimer and thrombin time. Compared with subcluster LC2, LC1 showed persistently greater symptom burden, functional impairment, reduced quality of life, lower resilience, and higher anxiety/depressive symptoms. Potential confounding by age, sex, comorbidities, and selected medication use was evaluated. Network and coexpression analyses identified regulatory nodes enriched for viral infection and natural killer cell activation pathways. A random forest classifier incorporating 9 miRNAs and LRRFIP2 achieved an area under the receiver operating characteristic curve of 0.91 for LC1, distinguishing LC1 from LC2 and recovered control participants.

Conclusions

LC comprises biologically and clinically distinct subclusters shaped by coordinated miRNA-mRNA remodeling. The immuno-hematopoietic LC1 subcluster supports biomarker-based stratification of patients with persistent physiologic and clinical impairment.

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综合mirnaome -转录组分析鉴定了长COVID患者的免疫造血亚群。

背景：SARS-CoV-2感染后的持续症状，称为COVID-19后状态或长COVID (LC)，会带来巨大的心理和社会经济负担。然而，LC异质性背后的miRNA-mRNA相互作用仍未完全确定。目的确定综合血液miRNA-mRNA分析是否能识别与临床和免疫造血功能相关的LC分子亚群。方法：我们对LC患者和康复对照组的循环血液RNA进行了综合mirnaome -转录组分析。使用LIMMA评估差异miRNA和mRNA表达，并使用分层聚类来定义LC亚簇。使用miRNet构建经过验证的miRNA-mRNA相互作用网络。临床、功能和生化参数在亚簇之间进行比较，并开发了随机森林分类器。结果聚类鉴定出一个免疫造血LC亚簇LC1，其特征是广泛的miRNA-mRNA失调，红细胞、血小板和免疫途径富集，生化改变包括血浆钠降低、纤维蛋白d -二聚体和凝血酶时间升高。与LC2相比，LC1表现出持续更大的症状负担、功能障碍、生活质量下降、更低的恢复力和更高的焦虑/抑郁症状。评估了年龄、性别、合并症和所选药物使用的潜在混淆。网络和共表达分析确定了病毒感染和自然杀伤细胞激活途径富集的调控节点。一个包含9个mirna和LRRFIP2的随机森林分类器对LC1的AUROC为0.91，将LC1与LC2和恢复对照区分开。结论lc由生物学和临床上不同的miRNA-mRNA协同重塑形成的亚簇组成。免疫造血LC1亚型支持基于生物标志物的持续生理和临床损伤患者分层。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Allergy and Clinical Immunology 医学-过敏

CiteScore

25.90

自引率

7.70%

发文量

1302

审稿时长

38 days

期刊介绍： The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.