Ongoing studies show that electrical vagus nerve stimulators can relieve some long 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 very important 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 and chemical organ,” says Peter Staats, co-president of the Vagus Nerve Society and co-founder of the neuromodulation company electroCore. “Modern medicine has focused on the chemical side of things. And it’s time to focus a little more on the electrical side.
Vagus nerve stimulation is already being used to treat a few other thorny neurological conditions. Implantable pacemakers were first approved for epilepsy in 1997 and for depression in 2005. But despite the promise of the procedure to treat long COVID, researchers say it may not be enough on its own. Long COVID is an unsolved conundrum, difficult to understand, let alone diagnose or treat. Symptoms vary greatly from individual to individual, and no single technique can deal with the viral consequences in the body. Experts say combination treatment seems to be the most productive way to get other people out of this chronic disease. But vagus nerve stimulation may simply be a niche tool in the arsenal of long COVID treatment. It has the potential to treat neurological symptoms in a way that limited drug responses have failed to achieve. not allowed so far.
“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 harnesses the vagus nerve’s healing power on command more easily. Some people may be able to reengage their own dysfunctional vagus nerve through mindfulness exercises, but most need an external aid. That includes many who live with long COVID, given that they often have severe tissue damage and depleted energy levels. “To tell somebody who has struggled with long COVID for three years and has seen 500 doctors to go do some mindfulness—that’s not going to go over well,” says Mayo Clinic internist Ravindra Ganesh, who is currently leading a clinical trial of vagus nerve stimulation for long COVID using electroCore devices.
In the early days of the pandemic, researchers temporarily detected that many of the symptoms of an acute COVID infection were similar to those of an uncontrolled vagus nerve. People hospitalized with COVID suffered what is known as the cytokine storm, in which the infection triggered an exaggerated and uncontrollable immune reaction that ultimately backfired and destroyed 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 discovered 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 shown that vagus nerve stimulation is maximally effective in reducing long-term debilitating COVID-related fatigue. The researchers were encouraged by the fact that some participants in those studies reported improvements, but noted that others did not. “There’s not a drug trial or anything I’ve done in all my years that makes a patient so smart that they no longer meet the criteria for chronic fatigue syndrome,” says Benjamin Natelson, a neurologist at Mount Sinai, who has conducted several clinical studies. on vagus nerve stimulation for physical conditions, some of which used electroCore and Parasym devices. (Natelson says he didn’t get studio investment from those 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; Several parasympathetic pathways are activated at the same time during stimulation. This may sound worrisome, however, researchers agree that there are many negative side effects similar to exaggerated parasympathetic action. If used correctly, the worst possible headaches are likely to be mild skin. Swelling from electric shocks or diarrhea from an overstimulated digestive system.
Vagal treatment still has clinical gaps to fill, so doctors are hesitant to prescribe it widely for long COVID before a confirmatory trial is completed. Scientists are still analyzing the main points of the treatment and adding the most productive delivery method. For example, ElectroCore’s strategy consists of a series of mild shocks with a handheld 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 this is where the vague package is thickest, making it the most effective stimulation site. Other researchers, in addition to those at Parasym, say that managing long COVID symptoms requires a longer stimulation time. These scientists point out that the end of a vagal branch ends at the folds of the ear. Using a hands-free headset clip can provide a convenient way to provide an hour of electrical stimulation during the day.
But electrical stimulation of the neck or ear may not activate the entire vagal spine, says Gemma Lladós, an infectious disease physician at Germany’s Trias i Pujol University Hospital in Spain. She suggests a more invasive approach: a device implanted under the skin directly into the vagal bundle to provide close, continuous 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 one glaring caveat to vagus nerve stimulation: the price. The electroCore device, for example, is offered on a pay-per-use basis that can cost a person more than $7,000 per year without any discounts. Parasym’s stimulator has a one-time price tag of €699 (approximately $770) and is only sold in Europe (though Natelson says some of the people he treats in the U.S have managed to purchase the device by using European addresses). U.S. regulators have approved electroCore’s device and some other companies’ versions as well—but exclusively for non-COVID-related problems such as migraines. People with long COVID can buy these products only if their physicians prescribe them off-label, and insurance companies are unlikely to cover the cost without specific approval for long COVID.
Researchers caution against trying to build one’s own device or purchasing untested versions on the Internet. Vagus nerve stimulation involves running an electrical current close to your heart or brain. “Let’s not mess with that,” Ganesh says. Approved medical devices are calibrated to be safe, but an unapproved device with incorrect settings could slow or stop the heart. In extreme cases, vagal tampering can lead to sudden death.
As with any long-term COVID therapy, the key is to ration energy levels based on the body’s limitations, Grach says. At the Mayo Clinic, he sees patients so excited to embark on a new treatment that they demand too much from their bodies and eventually “If you keep going over the reservoir that your body has,” Grach says, “you won’t end up feeling the benefits of the interventions anyway. “
Learn about and share the most exciting discoveries, innovations, and concepts shaping our world today.
Follow:
Scientific American is part of Springer Nature, which owns or has commercial relations with thousands of scientific publications (many of them can be found at www.springernature.com/us). Scientific American maintains a strict policy of editorial independence in reporting developments in science to our readers.
© 2023 SCIENTIFIC AMERICAN, A DIVISION OF SPRINGER NATURE AMERICA, INC. ALL RIGHTS RESERVED.