Identification of Altered Potassium Channels for Drug Repurposing in Long COVID Patients

Publication date: Jun 20, 2026

Long COVID (LC) is a complex condition characterized by persistent, chronic multisystem manifestations, with a significant proportion of patients exhibiting neurological symptoms. Human ion channels (HICs), particularly potassium channels, are abundantly expressed in the nervous system and linked to key metabolic processes, making them potential candidates for understanding LC pathophysiology and drug repurposing. Meta-analysis of RNA-Seq datasets from COVID-19 recovered and LC patients was performed to identify altered HICs in LC. Differential gene expression analysis, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA) were performed to uncover key genes, pathways, and co-expression modules consisting of HICs, lipid metabolism-, and immune signaling-related genes. Drug-gene interaction analysis was performed to identify approved drugs targeting potential HICs. A total of 715 dysregulated genes, including eighteen HICs were identified, among which seven were potassium channels. Three significant modules containing HICs, lipid metabolism-, and immune signaling-related genes were identified and found to be associated with antigen processing and presentation, complement and coagulation cascades, and cytokine-related pathways. Approved drugs targeting KCNA6, KCNJ10, KCNN3, and KCNH4 were identified. With further experimental validation, these dysregulated potassium channels, supported by their co-expression networks and pathway associations, may act as potential candidates for drug repurposing in LC patients.

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Concepts Keywords
Austria Channels
Drug87 Covid
Dyspnea Drug
June Expression
Remodeling Hics
Immune
Lipid
Metabolism
Pathways
Performed
Potassium
Potential
Related
Repurposing
Signaling

Semantics

Type Source Name
pathway REACTOME Potassium Channels
disease MESH Long COVID
disease MESH COVID-19
pathway KEGG Antigen processing and presentation
pathway KEGG Complement and coagulation cascades
disease MESH Park
pathway REACTOME Immune System
disease MESH viral infection
disease MESH channelopathies
disease MESH fatigue
disease MESH brain fog
disease MESH dyspnea
disease MESH chest pain
disease MESH inflammation
disease MESH infection
pathway REACTOME Signal Transduction
drug DRUGBANK Isoxaflutole
disease MESH Hypokalemia
drug DRUGBANK Potassium
disease MESH seizures
pathway KEGG Viral replication
pathway REACTOME Translation
disease MESH STAR
drug DRUGBANK Serine Vanadate

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