Chandelier
Senior Member (Voting Rights)
Vagal cholinergic denervation of the gastric mucosa in Long-COVID-19: in vivo evidence of structural autonomic dysfunction
• In the gastrointestinal tract vagal innervation plays a role in the inflammatory response through the cholinergic pathway.
• Cholinergic denervation in vivo in Long COVID-19 has never been demonstrated.
• Restoring or enhancing vagal function may be potential treatments.
Reduced vagal activity observed in these patients may reflect structural damage to autonomic fibers.
We hypothesized that dysautonomic manifestations in Long-COVID-19 are associated with impaired cholinergic innervation of the gastric mucosa.
Gastric mucosal biopsies were analyzed using immunohistochemistry with the pan-neuronal marker protein gene product 9.5 (PGP 9.5) and vasoactive intestinal peptide (VIP) as a marker of cholinergic fibers.
Nerve fiber density was quantified in both fundus and antrum samples.
The reduction in cholinergic innervation was more pronounced in the fundus (p<0.01) andalso evident in the antrum (p=0.01).
Gastric nerve density correlated with HRV parameters (LF/HF ratio: R=0.50, p<0.05) and NT-proBNP levels (R=0.52, p<0.01).
This structural autonomic impairment may represent an anatomical substrate underlying dysautonomia in Long-COVID-19.
Web | DOI | International Journal of Infectious Diseases | Open Access
Acanfora, Domenico; Nolano, Maria; Acanfora, Chiara; Colella, Camillo; Provitera, Vincenzo; Caporaso, Giuseppe; Rengo, Giuseppe; Incalzi, Raffaele Antonelli; Casucci, Gerardo
Highlights
• Last evidences support autonomic dysfunction in the pathophysiology of Long COVID-19.• In the gastrointestinal tract vagal innervation plays a role in the inflammatory response through the cholinergic pathway.
• Cholinergic denervation in vivo in Long COVID-19 has never been demonstrated.
• Restoring or enhancing vagal function may be potential treatments.
Abstract
Objectives
Dysautonomia has been increasingly recognized as a key feature of Long-COVID-19, potentially contributing to persistent gastrointestinal and systemic symptoms.Reduced vagal activity observed in these patients may reflect structural damage to autonomic fibers.
We hypothesized that dysautonomic manifestations in Long-COVID-19 are associated with impaired cholinergic innervation of the gastric mucosa.
Methods
We conducted a case–control study including 12 patients with Long-COVID-19 and 8 control subjects undergoing routine gastroscopy.Gastric mucosal biopsies were analyzed using immunohistochemistry with the pan-neuronal marker protein gene product 9.5 (PGP 9.5) and vasoactive intestinal peptide (VIP) as a marker of cholinergic fibers.
Nerve fiber density was quantified in both fundus and antrum samples.
Results
Compared with controls, Long-COVID-19 patients exhibited a significant reduction in mucosal innervation density: 2.1 vs 3.9 nm/µm³ (p<0.01) in the fundus and 1.9 vs 3.9 nm/µm³ (p<0.05) in the antrum.The reduction in cholinergic innervation was more pronounced in the fundus (p<0.01) andalso evident in the antrum (p=0.01).
Gastric nerve density correlated with HRV parameters (LF/HF ratio: R=0.50, p<0.05) and NT-proBNP levels (R=0.52, p<0.01).
Conclusions
Patients with Long-COVID-19 exhibit reduced gastric mucosal cholinergic innervation.This structural autonomic impairment may represent an anatomical substrate underlying dysautonomia in Long-COVID-19.
Web | DOI | International Journal of Infectious Diseases | Open Access