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Vagus Nerve Dysfunction in the Post-COVID-19 Condition
23 Pages Posted: 19 Jun 2023
More...Abstract
Background: The post-COVID-19 condition (PCC) is a disabling syndrome affecting 5-15% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some of the PCC symptoms, including persistent dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances or neurocognitive complaints.
Methods: We performed a cross-sectional pilot study in subjects with PCC with symptoms suggesting vagus nerve dysfunction (n=30) and compared them to subjects fully recovered from acute COVID-19 (n=14) and individuals never infected with SARS-CoV-2 (n=16), matched by age and sex. We evaluated the structure and function of the vagus nerve, including dysphonia, dysphagia, and dysautonomia tests, and evaluated the structure and function of respiratory muscles with vagus nerve innervation.
Findings: Participants were mostly (80%) women with median 44 years of age. Their most prevalent symptoms were cognitive dysfunction (83%), dyspnea (80%) and tachycardia (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (mean ± SD left vagus nerve cross-sectional area: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2, p=0.080), flattened diaphragmatic curve (47% vs 6% vs 14%, p=0.007), reduced esophageal peristalsis (34% vs 0% vs 21%, p=0.020), gastroesophageal reflux (34% vs 19% vs 7%, p=0.130), hiatal hernia (25% vs 0% vs 7%, p=0.050) and reduced maximal inspiratory pressure in functional respiratory tests (62% vs. 6% vs. 17%, p ≤0.001).
Interpretation: Vagus nerve dysfunction has a central pathogenic role in the pathophysiology of the post-COVID condition.
Funding: This work was partially funded by the crowdfunding initiative https://www.yomecorono.com. MM was granted with RYC2020-028934-I/AEI/10.13039/501100011033 from Spanish Ministry of Science and Innovation and State Research Agency, MCIN/AEI/10.13039/501100011033 and the European Social Fund “investing in your future”. FML was supported by a doctoral fellowship from Fundació Sorigué.
Declaration of Interest: The authors declare no conflicts of interest. CB is a shareholder of Electrocore Inc.
Ethical Approval: This study was approved by the Germans Trias Hospital Ethics Committee Board (HUGTiP/PI-21-184) and was conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent to participate.
Keywords: SARS-CoV-2, Post-COVID-19 Condition, persistent symptoms, vagus nerve, autonomic dysfunction
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