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Visium HD Spatial Transcriptomics Reveals Persistent SARS-CoV-2 Signaling in the Epipharynx and the Therapeutic…

In this study published in _Scientific Reports_ (2025), we applied **Visium HD spatial transcriptomics** to investigate the epipharyngeal tissue of patients with **long COVID**, focusing on persistent viral activity and local immune dysregulation.

We detected **residual SARS-CoV-2 RNA** in the epipharynx more than 6 months after infection, along with sustained activation of SARS-CoV-2-related signaling pathways in both epithelial and immune cell populations. Epithelial cells exhibited downregulation of cilia-related genes (_DNAI1_, _CFAP47_), while immune cells—especially B cells, plasma cells, and plasmacytoid dendritic cells—showed upregulation of antiviral and inflammatory pathways. These findings suggest that the epipharynx acts as a **chronic inflammatory reservoir** in long COVID.

To address this, we performed **epipharyngeal abrasive therapy (EAT)**—a Japanese outpatient technique using a zinc chloride-soaked swab to mechanically abrade the inflamed mucosa—once weekly for 3 months. After EAT, patients showed marked **clinical improvement**, paralleled by molecular-level changes: decreased expression of **inflammatory cytokines** (_IL6_, _TNF_), suppression of **T-cell receptor signaling**, and downregulation of **antibody-related genes** (_IGHM_, _IGHG3_). 

This is the **first study to provide spatial transcriptomic evidence** of persistent SARS-CoV-2 signaling in the epipharynx of long COVID patients. Moreover, our data suggest that EAT exerts **immune-modulatory and tissue-repair effects**, positioning it as a promising therapeutic option for managing long COVID, particularly in patients with upper airway-dominant symptoms.

📊 Dataset available at ArrayExpress: **E-MTAB-14669**

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