Hypothesis: Cervical Level Vagus Nerve Injury as Cause of COVID Lung

[McCamy Taylor]

What happens to lab animals if you sever their vagus nerves at the level of the neck? Answer: their lungs fill up with fluid, become stiff and they die.

We know that COVID gets into the central nervous system. One way it can gain access to the brain is via the olfactory nerves through the cribiform plate. But what if the virus also infects the vagus nerves that run down the neck, through the chest and finally into the abdomen? Other respiratory viruses such as influenza have been found to affect the vagus nerve in this way.

I have collected links to several articles about animal tests in which the vagus nerve is completely severed at the cervical level. The various animals--dogs, guinea pigs, rabbits, birds--do not live long. They develop pulmonary congestion and stiff lungs. They also have problems swallowing which can lead to aspiration. And their heart rates go through the roof while blood pressure drops.

Since neurological effects of COVID are not universal, this might explain why some people but not all develop the really severe type of COVID lung disease.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2133576/

https://journals.physiology.org/doi/abs/10.1152/ajplegacy.1976.230.3.777

https://journals.physiology.org/doi/abs/10.1152/ajplegacy.1949.157.1.130?journalCode=ajplegacy

https://www.sciencedirect.com/science/article/abs/pii/S1566070200002800

https://www.surgjournal.com/article/0039-6060(65)90111-X/fulltext

https://journals.physiology.org/doi/abs/10.1152/ajplegacy.1964.206.2.265

https://journals.physiology.org/doi/abs/10.1152/jappl.1986.61.5.1741

[Bernardo de La Paz]

1. You may be on to something. I wonder what doctors think of your hypothesis. Worth exploring. . . .nt

[McCamy Taylor]

2. I am sending it out to some doctors I know.

I have a Masters Public Health but I am in practice and do not do any research myself.

[Bernardo de La Paz]

3. Good! Let us know if you get any positive feedback. . . . nt

[crickets]

4. K&R for visibility.

[poli-junkie]

5. When you say injury to the Vagus Nerve

do you mean that the nerve has to be severed? What about a less-serious injury of the nerve -- like a bruising?

[McCamy Taylor]

6. In the lab studies they cut it completely.

We know that COVID can affect cranial nerves (like the vagus nerve) due to its affects on the olfactory nerve (no sense of smell). And I seem to recall hearing that it can cause other cranial nerve problems. In this case it would not be completely severed. But some viral nerve palsies can cause a complete loss of function for a while. For example, Bell's Palsy causes CN VII to stop working causing complete paralysis of one side of the face.

If someone was unfortunate enough to have complete bilateral vagus palsies, it would be like taking a lab animal and cutting both vagus nerves--rapid death. I have no idea what a complete palsy of a single nerve would do. Will look it up to see if there are any lab studies.

[McCamy Taylor]

7. Here's why knowing the physiology can help.

Experiment in which researchers were able to reverse the lung effects on vagotomy rabbits by giving surfactant.

https://journals.physiology.org/doi/abs/10.1152/jappl.1986.61.5.1741

Abstract:

We used the model of bilateral cervical vagotomy of adult rabbits to cause respiratory failure characterized by pulmonary edema, decreased lung compliance, and atelectasis. We documented an 18-fold increase in radiolabeled albumin leak from the vascular space into alveolar washes of vagotomy vs. sham-operated rabbits (P less than 0.01). Despite a twofold increase in percent of prelabeled saturated phosphatidylcholine secreted (P less than 0.01), the alveolar wash saturated phosphatidylcholine pool sizes were not different. The minimum surface tensions were 19.6 +/- 2.5 vs. 9.4 +/- 2.2 dyn/cm for alveolar washes from vagotomy and control rabbits, respectively (P less than 0.01). The soluble proteins from alveolar washes inhibited the surface tension lowering properties of natural surfactant, whereas those from the control rabbits did not (P less than 0.01). When vagotomy rabbits in respiratory failure were treated with 50 mg natural surfactant lipid per kilogram arterial blood gas values and compliances improved relative to control rabbits. Vagotomy results in alveolar pulmonary edema, and surfactant dysfunction despite normal surfactant pool sizes and respiratory failure. A surfactant treatment can improve the respiratory failure.

[TheBlackAdder]

8. Perhaps various neuropathies come into play, besides the ones noted for the lower extremities.

.

This might be explained by insulin resistant (ie. overweight w/belly fat), diabetics and others are predisposed to CV.

Also, I wonder if other neuropathies, such as HNPP are factors.

.

[McCamy Taylor]

9. Here is an article about right side cervical vagotomy

in lab animals and the effects on viral myocarditis. Note that nicotine was able to reverse the inflammatory effects that lack of vagal innervation caused. (Not recommending that anyone smoke)

https://www.frontiersin.org/articles/10.3389/fphar.2017.00025/full

The autonomic nervous system dysfunction with increased sympathetic activity and withdrawal of vagal activity may play an important role in the pathogenesis of viral myocarditis. The vagus nerve can modulate the immune response and control inflammation through a ‘cholinergic anti-inflammatory pathway’ dependent on the ?7-nicotinic acetylcholine receptor (?7nAChR). Although the role of ?-adrenergic stimulation on viral myocarditis has been investigated in our pervious studies, the direct effect of vagal tone in this setting has not been yet studied. Therefore, in the present study, we investigated the effects of cervical vagotomy in a murine model of viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of right cervical vagotomy and nAChR agonist nicotine on echocardiography, myocardial histopathology, viral RNA, and proinflammatory cytokine levels were studied. We found that right cervical vagotomy inhibited the cholinergic anti-inflammatory pathway, aggravated myocardial lesions, up-regulated the expression of TNF-?, IL-1?, and IL-6, and worsened the impaired left ventricular function in murine viral myocarditis, and these changes were reversed by co-treatment with nicotine by activating the cholinergic anti-inflammatory pathway. These results indicate that vagal nerve plays an important role in mediating the anti-inflammatory effect in viral myocarditis, and that cholinergic stimulation with nicotine also plays its peripheral anti-inflammatory role relying on ?7nAChR, without requirement for the integrity of vagal nerve in the model. The findings suggest that vagus nerve stimulation mediated inhibition of the inflammatory processes likely provide important benefits in myocarditis treatment.

[McCamy Taylor]

10. And here is an experiment involving peritonitis

in which the animals either got no treatment, got a unilateral vagotomy or got vagotomy plus nicotine (which activates the nerve receptors that the vagus nerve would have activated)

Animals with vagotomy had more inflammation and tissue death. Those with vagotomy pre-treated with nicotine has less inflammation and tissue death.

https://www.jstor.org/stable/30077878?seq=1

And again, do not inhale a house fire (i.e smoke cigarettes) That will do your lungs no good. Smokers do worse with COVID. But doctors might want to try cholenergic agonists like nicotine to see if they can suppress the immune response that is killing some people.

[McCamy Taylor]

11. Great article which raises the possibility that COVID kills due to CNS affects

https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.14275


The whole thing is available online as a PFD. This part caught my eye

" the virus may travel retrogradely along the vagus nerve, which innervates many of the visceral organs that can be invaded by the virus beyond the lungs, such as the heart and the gastrointestinal tract. Once in the vagal nerve endings, retrograde axonal transport may grant access to the brainstem"

[McCamy Taylor]

12. One more good speculative article about COVID and CNS

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mds.28067

[McCamy Taylor]

13. "Frostbite toe" a skin manifestation of COVID supports this theory

https://www.washingtonpost.com/health/2020/04/29/coronavirus-rashes-toes/?fbclid=IwAR26DhJghjBIxjbuhpOvTi7zumRlbl-AkQFkfsfvbHj88C_mWDfzc1Z-2IE

As a dermatologist at Massachusetts General Hospital in Boston, Esther Freeman was prepared for things to be a bit quieter during the pandemic lockdown. But not too long after it began, she started getting urgent calls about odd frostbite-like patches showing up on people’s toes.

The rash itself was rather harmless.

While some complained of a burning sensation, the inflammation usually disappeared on its own in two to three weeks without treatment. What was striking is that many of those patients had tested positive for covid-19.

What happens when you body loses vagal (parasympathetic) tone? The sympathetic takes over. And one of the things the so called "fight or flight" system does is shunt blood to the heart and lungs and brain and shut down blood flow to the periphery--like the toes. So if the vagus nerve is damaged, extremities might be underperfused leading to tiny areas of gangrene or "frost bite".

[McCamy Taylor]

14. Vagal Neuropathy after Viral URI exists!

Check out this link

https://www.sciencedirect.com/science/article/abs/pii/S0196070901276650

To describe a condition that occurs following an upper respiratory illness, which represents injury to various branches of the vagus nerve. Patients with this condition may present with breathy dysphonia, vocal fatigue, effortful phonation, odynophonia, cough, globus, and/or dysphagia, lasting long after resolution of the acute viral illness. The patterns of symptoms and findings in this condition are consistent with the hypothesis that viral infection causes or triggers vagal dysfunction. This so-called postviral vagal neuropathy (PVVN) appears to have similarities with other postviral neuropathic disorders, such as glossopharyngeal neuralgia and Bell's palsy.

As I posted in the OP above, enough damage to the vagus nerve at the cervical (throat) level causes pulmonary congestion and death. Milder degrees of damage can impair swallowing leading to aspiration which can cause pneumonia. According to this article, injury to the vagal nerve after viral infection has been documented in the past.

I really think it is time for the neurologists to step in and investigate the neurological effects of COVID more thoroughly.