vagus nerve infection – American ME and CFS Society

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.

Source:Woo MS, Shafiq M, Fitzek A, Dottermusch M, Altmeppen H, Mohammadi B, Mayer C, Bal LC, Raich L, Matschke J, Krasemann S, Pfefferle S, Brehm TT, Lütgehetmann M, Schädler J, Addo MM, Schulze Zur Wiesch J, Ondruschka B, Friese MA, Glatzel M. Vagus nerve inflammation contributes to dysautonomia in COVID-19. Acta Neuropathol. 2023 Jul 15. doi: 10.1007/s00401-023-02612-x. Epub ahead of print. PMID: 37452829. https://link.springer.com/article/10.1007/s00401-023-02612-x (Full text)

Abstract:

Chronic fatigue syndrome (CFS) is an often-debilitating condition of unknown origin. There is a general consensus among CFS researchers that the symptoms seem to reflect an ongoing immune response, perhaps due to viral infection. Thus, most CFS research has focused upon trying to uncover that putative immune system dysfunction or specific pathogenic agent. However, no single causative agent has been found.

In this speculative article, I describe a new hypothesis for the etiology of CFS: infection of the vagus nerve. When immune cells of otherwise healthy individuals detect any peripheral infection, they release proinflammatory cytokines. Chemoreceptors of the sensory vagus nerve detect these localized proinflammatory cytokines, and send a signal to the brain to initiate sickness behavior. Sickness behavior is an involuntary response that includes fatigue, fever, myalgia, depression, and other symptoms that overlap with CFS.

The vagus nerve infection hypothesis of CFS contends that CFS symptoms are a pathologically exaggerated version of normal sickness behavior that can occur when sensory vagal ganglia or paraganglia are themselves infected with any virus or bacteria. Drawing upon relevant findings from the neuropathic pain literature, I explain how pathogen-activated glial cells can bombard the sensory vagus nerve with proinflammatory cytokines and other neuroexcitatory substances, initiating an exaggerated and intractable sickness behavior signal. According to this hypothesis, any pathogenic infection of the vagus nerve can cause CFS, which resolves the ongoing controversy about finding a single pathogen. The vagus nerve infection hypothesis offers testable hypotheses for researchers, animal models, and specific treatment strategies.

Source: VanElzakker MB. Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis. Med Hypotheses. 2013 Sep;81(3):414-23. doi: 10.1016/j.mehy.2013.05.034. Epub 2013 Jun 19. https://www.ncbi.nlm.nih.gov/pubmed/23790471