This case-control study evaluated gastric mucosal cholinergic innervation in 12 Long-COVID-19 patients vs. 8 controls undergoing routine gastroscopy, using immunohistochemistry (PGP 9.5 and VIP markers) to quantify nerve fiber density in the gastric fundus and antrum.
Long-COVID-19 patients had significantly lower mucosal innervation density than controls in both the fundus (2.1 vs. 3.9 nm/µm³, p<0.01) and antrum (1.9 vs. 3.9 nm/µm³, p<0.05). Gastric nerve density correlated with HRV (LF/HF ratio: R=0.50, p<0.05) and NT-proBNP levels (R=0.52, p<0.01).
- Very small sample size (12 cases, 8 controls) limits statistical power and generalizability. - Cross-sectional design prevents causal inference or assessment of recovery over time. - Biopsies were obtained during routine gastroscopy, so selection bias and confounding by underlying GI conditions cannot be excluded.
Clinicians should be aware that Long-COVID-19 dysautonomia may have a structural basis — reduced cholinergic nerve fibers in the gastric mucosa — not just a functional one. Gastric mucosal biopsy with neuronal markers could be a future tool for objectively assessing autonomic injury in this population, pending validation in larger studies.
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