Post Viral Support for the Nervous System
COVID
IMMUNITY
(Including Vagus)
By Lynn Toohey, PhD
As we roll out a new year in 2023, we can look at how research has now accumulated concerning the unique immune challenges faced during a pandemic. Some of these challenges continue to present in multiple insidious ways as we realize how deeply COVID-19 upset the equilibrium of so many organ systems. There are many paths to explore in assessing the damage when it comes to the sequelae generated by “long COVID”; the focus here is on two particular nervous system effects.
The first focus is on sudden-onset narcolepsy, and the second focus is on sudden-onset vertigo. In the field of health care, one is asked questions daily that involve examining differentials and connecting dots before considering what nutritional protocol might be most efficacious. I recently was approached with two different case studies, and it turned out that what they had in common was suffering from the long COVID effects on the nervous system.
As COVID evolved, so did much of the research. In the beginning, scientists were hesitant to say conclusively that COVID was damaging the nervous system and causing side effects lasting beyond the infection. The theory has gained wide acceptance, and the connection has become very apparent.
The first case involves a 50-year-old male (doctor of chiropractic) with a fairly sudden onset of narcolepsy attacks. After reviewing his history, which didn’t appear to contain any clues as to why this sudden onset occurred, I mentioned that the flu or flu vaccine could be a trigger. In fact, an increase in narcolepsy diagnoses was particularly evident following the influenza-A H1N1 pandemic in 2009 and was evident in patients affected by influenza-A H1N1 and in patients vaccinated against this virus with Pandemrix (an adjuvanted Vaccine). (Schirinzi T, et al. COVID-19: Dealing with a potential risk factor for chronic neurological disorders. J Neurol. 2021 Apr;268(4):1171-1178.) It was revealed that the doctor in the case study had come down with a bad case of COVID, which sent me researching the relationship between COVID and narcolepsy. Sure enough, several scientific articles noted the relationship of long COVID to nerve damage that prevented the release of orexin. Orexin, also known as hypocretin, is a neuropeptide that regulates wakefulness. There are 50,000 to 80,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus.
The most common form of narcolepsy, in which the individual experiences brief losses of muscle tone, is caused by a lack of orexin in the brain because of destruction of the cells that produce it. It is believed that COVID can damage these orexin-producing cells, leading to narcoleptic attacks.
In April 2021, Schirinzi et al. stated, “Available data on COVID-19 currently disclosed that SARS-CoV2 can induce, directly or indirectly, a number of clinical manifestations and immune-inflammatory events, including viral-host interactions, that might shape pathogenic mechanisms underlying common chronic neuroinflammatory and neurodegenerative disorders.” (Schirinzi T, et al. 2021 ibid.) The authors go on to include narcolepsy as one of these resulting events because of the destruction of the orexin-producing cells. The researchers noted that COVID can cause tissue colonization in the gut and the central nervous system (CNS), leading to chronic problems. Gastrointestinal enterocytes represent major target cells of COVID, reacting to the infection with a strong inflammatory response, and local gut inflammation can lead to systemic inflammation.
They point out that CNS colonization by COVID has been proven, and they propose that COVID invades the brain through the olfactory tracts (which are suspected to provide an efficient port for neuroinvasion) and spreads toward the piriform and infralimbic cortex, the basal ganglia, and the brainstem. Unfortunately, some who experience loss of smell never recover it, depending on the extent of damage to the olfactory nerves. In this line of thinking, proinflammatory cytokines promote the migration of T cells that can damage the orexin hypothalamic neurons. The documentation of olfactory dysfunction in patients with narcolepsy
reinforces this hypothesis. (Bayard s, et al. Olfactory dysfunction in narcolepsy with cataplexy. Sleep Med. 2010;11:876-881.)
“The main message of this review to sleep medicine clinicians and researchers is to consider SARS-CoV2 infection as a possibly triggering event leading to narcolepsy.” (Schirinzi T, et at. 2021 ibid)
Nutritional recommendations to support this post-viral problem (narcolepsy) address the health and function of the nerves. There are many nerve-support nutrients, but some of my favorites are fish oil, curcumin, resveratrol, quercetin, and benfotiamine.
Fish Oil: High-quality fish oil with high EPA and DHA content (preferably 2:1 ratio of EPA to DHA) is very supportive and nourishing to nerves. Long-chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity at different stages of COVID infection. Omega-3 fatty acids, particularly EPA, reduce pro-inflammatory cytokines, equalize the HPA axis, and modulate neurotransmission. In addition, omega-3s and their metabolites restore tissue homeostasis, “and therefore, offer a promising strategy for long COVID. In this article, we explore in a systematic review the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID on the brain, behavior, and immunity.” (Yang
CP, et al. Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19. Brain Behav Irnmun. 2022 Jul;103:19-27.)
Curcumin: It has been stated that curcumin exerts its neural beneficial effects mostly by the role it plays in regulating the gut microbiome and, therefore, the microbiota-gut-brain-axis (MGB). (Zhang F, etal. Curcumin Alleviates DSS-Induced Anxiety-Like Behaviors via the Microbial-Brain-Gut Axis. Oxid Med Cell Longev. 2022 Mar 18:2022:6244757.) Curcumin also increases phosphatidylcholine (a major component of the nerve sheath). Curcumin may also help in the recovery period after nerve injury. (Wang G, et ah Curcumin enhances the proliferation and myelinization of Schwann cells through Runx2 to repair sciatic nerve injury. Neurosci Lett. 2022 Jan 23:770:136391.)
Resveratrol: Spinal cord nerve injury can change the intestinal microbiota pattern and corresponding metabolites, which in turn affect the prognosis for recovery. However, an interesting proposed mechanism of a beneficial action of resveratrol is that it works to improve the intestinal microbiota composition. (He N, et al. Resveratrol suppresses microglial activation and promotes functional recovery of traumatic spinal cord via improving intestinal microbiota. Pharmacol Res. 2022 Sep;183:106377.) The same researchers noted, “Resveratrol restored microbiota pattern, reversed intestinal dysbiosis, and increased the concentration of butyrate (a short-chain fatty acid, or SCFA)... SCFAs are ‘critical for neurological recovery.’”
Benfotiamine: A form of thiamine with a high bioavailability, benfotiamine has been used in many clinical trials to show its efficacy and support for damaged nerve recovery. One such study had results exhibiting excellent support characteristics for nerve health. (Bonhof GJ, et al. BOND study: A randomized double-blind, placebo-controlled trial over 12 months to assess the effects of benfotiamine on morphometric, neurophysiological, and clinical measures in patients with type 2 diabetes with symptomatic polyneuropathy. BMJ Open. 2022 Feb ,3;12(2):e057142.)
The second case involves a 35-year-old woman who started experiencing vertigo episodes for the first time. Again, COVID seemed to fit the bill after examining history and differentials. COVID’s long-term effects on the nervous system, and in particular the vagus nerve, are of interest to chiropractors. Chiropractors favorably influence the vagal tone that controls parasympathetic activity when they adjust patients. The vagus nerve produces the neurotransmitter acetylcholine (anti-inflammatory, connected to brain function, etc.) The vagus nerve supplies multiple organs, including the heart, lungs, intestines, and swallowing muscles.
Research presented at the European Congress of Clinical Microbiology and Infectious Diseases (2022, Lisbon, 23-26 April) suggested that many of the symptoms connected to long COVID can be linked to the effect of the virus on the vagus nerve — “one of the most important multifunctional nerves in the body.” The study was conducted by Dr. Gemma Llados and Dr. Lourdes Mateu from the University Hospital Germans Trias i Pujol, Badalona, Spain, and colleagues.
These doctors did a long-COVID study of 348 patients and found that 66% had at least one symptom suggesting vagus nerve dysfunction. From there, they divided the subjects into a subset of 22 people — most of them suffered from three or more symptoms related to vagus nerve dysfunction (average length of symptoms 14 months).
Six of the 22 patients had a change in the vagus nerve in the neck, which the researchers observed by ultrasound, involving thickening of the vagus nerve and increased inflammation. Furthermore, 10 of the 22 patients had flattened “diaphragmatic curves” during a thoracic ultrasound and had abnormal breathing. “Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID.”
In a pilot study, electrical stimulation of the vagus nerve (in the ear) was employed to address vertigo, among other long COVID symptoms and trends in the data that suggested improvements in all symptoms.
(Badran BW, et al. A pilot randomized controlled trial of supervised, athome, self-administered transcutaneous auricular vagus nerv e stimulation to manage long COVID symptoms. Res Sq [Preprint]. 2022 Jun 21.)
Electrical stimulation of the ear is just one way to increase vagal tone (of course, chiropractic is one!) The lists to “correct the cholinergic anti-inflammatory pathway” and to correct “vagal immune and autonomic modulation” can be found by locating the article written by Richard Belli, DC, in the October 2022 issue of The American Chiropractor titled, “Applied Kinesiology Approach to Vagus Nerve Dysfunction” (www. americanchiropractor. com).
Exercises that can be done at home by the patient include:
• Gargling, rubbing the abdomen, abdominal pressure, humming, or repeating the sound “om” (the vagus nerve innervates vocal cords).
• Slow rhythmic diaphragmatic breathing.
• Meditation, especially loving kindness meditation.
• Have patient perform activity three times a day for as many weeks as it takes to correct dysfunction.
Dr. Belli is the current president of the International College of Applied Kinesiology. His recommendations for increasing vagal tone include nutritional supplementation, most notably those nutrients already mentioned, plus choline and probiotics.
Choline is a precursor to the neurotransmitter acetylcholine secreted by the vagus nerve. So-called designer cholines can be utilized, such as alpha glyceryl phosphoryl choline or CDP choline. These cholines cross the blood-brain barrier and are extremely efficacious in raising choline levels.
Probiotics regulate the M-G-B (microbiota-gut-brain) axis and, in doing so, help balance the cellular environment of intestinal and systemic systems. The neuroendocrine secretions from the gut that interact with the vagus nerve and CNS are supported and reinforced by probiotics. In fact, a systematic review confirmed, “Probiotics showed efficacy in improving... (a long list of CNS functions follows). ” (Wang H, et at. Effect of Probiotics on Central Nervous System Functions: A Systematic Review. J Neurogastroenterol Motif 2016 Oct 30;22(4):589-605.)
Dr. Belli’s recommendations also include stimulating the auricular branch of the vagus nerve (similar to the pilot study) with a TENS unit or other forms of electrostim.
Transcutaneous vagus nerve stimulation therapy has been suggested as a highly effective, noninvasive way to manage persistent vertigo in people who suffer from geotropic DCPN (direction-changing positional nystagmus), which occurs when people suffering from this condition turn their head to the side.
In Conclusion:
Theories regarding the mechanisms by which the systemic inflammation of COVID affects the central nervous system include neuroinflammation caused by inflammatory cells crossing the blood-brain barrier and the involvement of various autoantibodies. Theories also include damage to the mitochondria, our energy-producing cells.
In conversation with a functional medicine expert,
Brandon Lundell DC, DABCI, APC, IFMCP, Dipl. Ac., we discussed how he has successfully addressed many cases by looking at mitochondriopathies that he believes are responsible for a lot of the fatigue and brain problems resulting from long COVID. Scientists would agree (and have proven with imaging studies) that long COVID cases present with decreased glucose metabolism and progressive brain atrophy (reflective of mitochondriopathies). (Watanabe H, et al. Long COVID: Pathogenesis and Therapeutic Approach. Brain Nerve. 2022 Jul;74(7):879884.)
We are just seeing the tip of the iceberg, as it were, as more of the CNS sequelae from long COVID are revealed. Planned follow-up articles will help explain some of the immune and inflammatory repercussions of the viral pandemic.
Dr. Lynn Toohey organizes seminars, acts as a nutritional consultant to Nutri-West (www.nutriwest.com) and authored the Functional Health Evaluation program that analyzes blood tests and DNA raw data (www.FHEcloud.com). Dr. Toohey can be reached at [email protected] with any questions.
