Ongoing studies show that electrical vagus nerve stimulators could alleviate some prolonged COVID symptoms. But are expensive devices worth it?
By Shi En Kim
Sebastian Kaulitzki/Scientific Photo Library
Can a disease as serious and disparate as COVID be treated without medication? Social media is abuzz with an experimental treatment that exploits the vagus nerve, which acts as the body’s “information highway” by transporting critical signals between the brain and internal organs. A mild electrical shock to this long cranial nerve triggers a wave of rest-related autonomic responses and can confer fitness benefits far beyond.
Researchers are increasingly finding that long COVID is as much a neurological disorder as it is a cardiovascular and respiratory disorder. Therapeutic studies have highlighted neurological facets of the disease, some of which would possibly be similar to the vagus nerve. The first small-scale vagal stimulation studies found relief in the characteristic symptoms of long COVID, such as chronic fatigue, headaches, and abnormal blood pressure. Another study showed that devices used to send electrical stimulation through the skin are safe and easy to use at home, offering convenience. accessibility and lower risk of contagion. Scientists are still reading what long COVID symptoms this strategy can reliably treat, which patients will gain advantages, and how long the effects last. Regardless, the influence of the vagus nerve on the framework appears to be key to treating some of the general manifestations of long COVID.
“Your body is an electrical, chemical organ,” says Peter Staats, co-president of the Vagus Nerve Society and co-founder of neuromodulation company electroCore. “Modern medicine has focused on the chemical aspect of things. And it’s time to focus a little more on the electric aspect.
Vagus nerve stimulation is already used to treat some other thorny neurological conditions. Implantable stimulators were first approved for epilepsy in 1997 and for depression in 2005. But despite the procedure’s promise for treating long COVID, researchers say it won’t be enough on its own. Long COVID is an unresolved enigma that’s tricky to understand, let alone diagnose or treat. Symptoms vary wildly between individuals, and no single approach can address the viral aftermath throughout the body. Experts say combination therapy appears best for lifting people out of this chronic condition. But vagus nerve stimulation could be a niche tool in the long COVID treatment arsenal. It has potential to address neurological symptoms in a way that limited pharmacological solutions so far have not.
“Whenever we have a single treatment option, we’re often hesitant to say it’s going to be the panacea,” says Stephanie Grach, an internist at the Mayo Clinic. But “right now, almost any care or treatment option that can help a safe number of other people is a game changer. “
The vagus nerve, a collection of fibers that run from the brainstem and around the body, is the entrepreneur of our involuntary processes and organ functions. It is also part of the parasympathetic nerve formula, responsible for calming the body after a stressful situation. event. During this recovery phase, the core rate slows to normal, the immune formula lets its guard down, and the digestive formula restarts. The vagus nerve acts as a “stopping” transference to the fight-or-flight mode of the sympathetic formula. This nerve is also activated in activities such as yoga, meditation, and slow breathing, which usually leave practitioners calm and rested.
Electrical stimulation more gently harnesses the healing force of the vagus nerve when commanded. Some other people could possibly reactivate their own dysfunctional vagus nerve through mindfulness exercises, but most need outside help. This includes many other people living with long COVID, given that they have severe tissue damage and depleted strength levels. “To tell someone who has struggled with long COVID for 3 years and went to 500 doctors to come in and do mindfulness, that’s not going well,” says Ravindra Ganesh. , an internist at the Mayo Clinic, who recently led a clinical trial of vagus nerve stimulation for long COVID using electroCore devices.
During the early days of the pandemic, researchers quickly noticed that several symptoms of acute COVID infection were similar to those of the vagus nerve going haywire. People hospitalized with COVID often suffered from the so-called cytokine storm, in which the infection triggered an excessive, runaway immune response that eventually turned inward to wreck the host’s own tissues.
After the initial infection subsided, a high percentage of people with long COVID still reported symptoms seen with vagal dysfunction. And last June, researchers uncovered irrefutable evidence: Autopsies of people who died with COVID revealed viral RNA and inflammatory cells in vagal tissue, indicating that the virus had infiltrated and ruptured this key nerve.
For many researchers, reviving a degraded vagus nerve seemed like an apparent solution to treating long COVID. “It’s a basic nerve,” says Michael VanElzakker, a neuroscientist at Massachusetts General Hospital. Approaching it as a healing technique “should be considered as and deserves further investigation. “
Researchers claim that vagus nerve stimulation weakens widespread COVID symptoms by opening up the body’s parasympathetic pathways. A sign of increased sympathetic activity is when the immune formula continues to work, even after the initial infection is over. The vagus nerve calms this overactive defense by cutting off the production of cytokines, signaling chemicals that announce inflammation. In 2000, researchers discovered the anti-inflammatory role of the vagus nerve when they found that its stimulation reduced fatal septic shock in rats exposed to bacterial toxins. Many scientists who reactivate the vagus nerve could also restore immunity in others with acute or chronic COVID symptoms.
According to Elisabetta Burchi, head of translational studies at neuromodulation startup Parasym, waking up the vagus nerve component that enters the brainstem may also involve nearby cortical spaces involved in memory and attention. Such stimulation triggers a release of chemical neurotransmitters, which can reduce the neurocognitive effects of COVID in the long term. However, the evidence is still inconclusive. An initial study awaiting peer review found that vagal stimulation had only a minimal effect on “brain fog,” a commonly reported symptom in long COVID.
So far pilot studies have demonstrated that vagus nerve stimulation works best for reducing long COVID’s debilitating fatigue. Researchers have been encouraged that some participants in these studies reported improvements—but they have noted that some did not. “There is no trial of any drug or anything I’ve ever done in all my years that makes a patient so well that he or she no longer fulfills criteria for chronic fatigue syndrome,” says Benjamin Natelson, a neurologist at Mount Sinai, who has run several clinical studies on vagus nerve stimulation for various health conditions, some of which used devices from electroCore and Parasym. (Natelson says he did not receive funding for the studies from these companies.)
Because the vagus nerve is made up of many fibers, researchers can’t control which individual fiber is activated to target a specific organ; During stimulation, several parasympathetic pathways are activated at the same time. This may seem worrisome, but researchers agree that there are many negative side effects due to excessive parasympathetic action. If such a device is used correctly, the worst headaches likely to be mild skin inflammation from electric shocks or diarrhea from an overstimulated digestive system.
The vagal treatment still has clinical gaps to fill, so doctors are hesitant to prescribe it widely for long COVID until a confirmatory trial is complete. Scientists are still analyzing the main points of treatment, adding the most productive delivery approach. For example, ElectroCore’s strategy is made up of a series of light shocks with a wearable device that a user can touch on either side of the neck for a few minutes each day. Staats, the company’s co-founder, says that’s where the wavebeam is thickest. , making it the site of maximum effective stimulation. Other researchers, in addition to those at Parasym, say that controlling the symptoms of long COVID requires a longer stimulation time. These scientists locate that the tip of a vagal branch ends at the folds of the ear. Using a hands-free clip similar to a headset can be a convenient way to provide an hour of electrical stimulation during the day.
But electrical stimulation of the neck or ear might not activate the entire vagal spine, says Gemma Lladós, an infectious disease physician at the German Trias i Pujol University Hospital in Spain. She suggests a more invasive approach: a device implanted under the skin directly over the vagal bundle to provide close, uninterrupted stimulation, similar to implants for epilepsy and depression. Lladós’ team is finalizing plans for a clinical study until 2024 on the treatment of long COVID with a vagus nerve implant.
There’s also an obvious caveat to vagus nerve stimulation: value. The electroCore device, for example, is offered with a pay-as-you-go system that can charge the user more than $7,000 a year without any discounts. The Parasym stimulator retails for 699 euros (about $770) and is only sold in Europe (although Natelson says some of the other people he treats in the U. S. have monitored purchasing the device in European addresses). Regulators have also approved ElectroCore’s device, as well as versions from some other corporations, but exclusively for non-COVID-related problems such as migraines. People with long COVID can only purchase such products if their doctors prescribe them without authorization, and insurance corporations are unlikely to charge them without express approval for long COVID.
Researchers advise against building your own device or buying untested versions on the internet. Vagus nerve stimulation involves passing an electrical current near your center or brain. “Let’s not dwell on that,” says Ganesh. Approved medical devices are calibrated to be safe, however, a device with unapproved configurations may simply slow down or impede the operation of the facility. In excessive cases, vagal disturbance can lead to sudden death.
As with any long COVID therapy, the key is pacing to ration one’s energy levels according to the body’s limits, Grach says. At the Mayo Clinic, she often sees patients who are so excited to embark on a new treatment that they push their body too far and eventually crash. “If you continue to push past the reserve that your body has,” Grach says, “you’re not going to end up feeling the benefit of the interventions regardless.”
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