186: TNFα–TGFβ Axis Disrupts Nasal Epithelium in Post‑COVID Syndrome

️ Episode 186: TNFα–TGFβ Axis Disrupts Nasal Epithelium in Post‑COVID Syndrome

In this episode of PaperCast Base by Base, we explore a single‑cell RNA‑seq study of nasal biopsies showing that persistent immune signaling—not residual virus—drives aberrant epithelial differentiation in people with post‑COVID syndrome. fileciteturn1file0

Study Highlights:
Researchers profiled >56,000 cells from nasal tissue of individuals with moderate or severe post‑COVID syndrome, revealing marked depletion of proximal ciliated cells alongside expansion of basal and immune cell populations. Cell–cell communication and pathway analyses identified heightened TNFα and TGFβ signaling, with MIF–CD74 interactions and downstream NF‑κB/EGFR activity linking immune cells to epithelial remodeling. The team validated causality in air‑liquid interface cultures, where exposure to TGFβ and TNFα—alone and especially in combination—reduced ciliated‑cell differentiation and promoted basal‑cell skewing and EMT‑like programs. Viral RNA was undetectable in biopsies and inflammatory markers typical of acute infection were not elevated, indicating pathology independent of ongoing viral load.

Conclusion:
Targeting the TNFα–TGFβ inflammatory axis may help restore normal epithelial differentiation and mitigate respiratory comorbidities in severe post‑COVID syndrome.

Reference:
Reddy KD, Maluje Y, Ott F, Saurabh R, Schaaf A, Bohnhorst A, et al. scRNA‑seq reveals persistent aberrant differentiation of nasal epithelium driven by TNFα and TGFβ in post‑COVID syndrome. Nature Communications. 2025;16:9494. https://doi.org/10.1038/s41467-025-64778-0

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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