Vagus nerve inflammation contributes to dysautonomia in COVID-19
Marcel S. Woo, Mohsin Shafiq, Antonia Fitzek, Matthias Dottermusch, Hermann C. Altmeppen, Behnam Mohammadi, Christina Mayer, Lukas C. Bal, Lukas Raich, Jakob Matschke, Susanne Krasemann, Susanne Pfefferle, Thomas Theo Brehm, Marc Lütgehetmann, Julia Schädler, Marylyn M. Addo, Julian Schulze zur Wiesch, Benjamin Ondruschka, Manuel A. Friese, Markus Glatzel
Abstract
Dysautonomia has substantially impacted acute COVID-19 severity as well as symptom burden after recovery from COVID-19 (long COVID), yet the underlying causes remain unknown. Here, we hypothesized that vagus nerves are affected in COVID-19 which might contribute to autonomic dysfunction. We performed a histopathological characterization of postmortem vagus nerves from COVID-19 patients and controls, and detected SARS-CoV-2 RNA together with inflammatory cell infiltration composed primarily of monocytes. Furthermore, we performed RNA sequencing which revealed a strong inflammatory response of neurons, endothelial cells, and Schwann cells which correlated with SARS-CoV-2 RNA load. Lastly, we screened a clinical cohort of 323 patients to detect a clinical phenotype of vagus nerve affection and found a decreased respiratory rate in non-survivors of critical COVID-19. Our data suggest that SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction which contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.