Vagus nerve inflammation contributes to dysautonomia in COVID-19

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.

Long-term effects of COVID-19 on endothelial function, arterial stiffness, and blood pressure in college students: a pre-post-controlled study

“…This may be attributed to the fact that our subjects consisted of young college students, and none of them were hospitalized due to COVID-19 infection. A recent study had indicated that SARS-CoV-2 induced vagal neuropathy, leading to autonomic dysfunction and potential long-term impairment of autonomic function (44) . Additionally, a study found that SARS-CoV-2 infection increased sympathetic nerve activation in young individuals, but had no signi cant effect on resting hemodynamics and speculated that the impact of COVID-19 on endothelial function and arterial stiffness may be more pronounced in older individuals (45) .…”

Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study

“…Likewise, fatigue and airway disorders in long COVID patients are other symptoms that have been associated with dysautonomia [ 12 ]. In particular, the latest studies suggest that SARS-CoV-2 may induce vagus nerve inflammation followed by autonomic dysfunction, which might contribute to critical disease courses and dysautonomia observed in long COVID [ 34 ].…”

Auricular acupuncture for persistent insomnia and anxiety associated with COVID-19: a case report

“…Regarding the acupoint selection in this case report, previous studies have indicated that acupuncture at sympathetic (AH6a), shenmen (TF4), and point zero could regulate sympathetic nerve functions and induce parasympathetic activation to improve insomnia ( 10 ). Moreover, given that vagal dysregulation is an important contributor to post-COVID sequelae ( 11 ), needling at point zero, which is located along the distribution paths of the auricular branch of the vagus nerve (ABVN), can neuromodulate the vagus nerve to treat psychiatric symptoms in this patient. In addition, a previous research study has revealed that needling at point zero can create a sense of calmness and homeostasis, thereby relieving anxiety ( 12 ).…”