COVID-19 Vagus Nerve Inflammation May Lead to Dysautonomia: New Study

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For those experiencing persistent symptoms long after their bout with COVID-19 has ended—including fatigue, lightheadedness, brain fog, cognitive issues, gastrointestinal problems, heart palpitations, shortness of breath, or an inability to tolerate upright postures—new data may provide answers.

SARS-CoV-2 infection may damage the nerves of the autonomic nervous system (ANS), causing an inflammatory response that can later lead to dysautonomia observed in long COVID patients, a July 15 study published in Acta Neuropathologica suggests.

Study Findings

Using several methods, researchers at the University Medical Center Hamburg-Eppendorf in Germany performed a microscopic analysis of the vagus nerves in 27 deceased patients with COVID-19 and five others who died of other causes, without COVID-19.

The vagus nerve is a vital component of the ANS that regulates critical functions such as digestion, respiratory and heart rate, and immune response. Vagus nerve signaling to the brainstem also controls the “sickness behavior response,” where the brain mounts flu-like symptoms that include nausea, fatigue, pain, and other chronic symptoms in response to inflammation.

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The researchers detected SARS-CoV-2 RNA in vagus nerve samples obtained from deceased patients with severe COVID-19 showing direct infection of the nerve was accompanied by inflammatory cell infiltration composed mostly of monocytes—a type of white blood cell that finds and destroys germs and eliminates infected cells. Their analysis revealed a “strong enrichment of genes regulating antiviral responses and interferon signaling,” supporting the idea that vagus nerve inflammation is a common phenomenon with COVID-19.

The researchers also analyzed 23 vagus nerve samples of deceased COVID-19 patients grouped into low, intermediate, and high SARS-CoV-2 RNA viral load to determine if the virus was directly detectable in the vagus nerve and if the viral load correlated with vagus nerve dysfunction. Results showed the virus was present in the vagus nerve and also determined there was a direct correlation between SARS-CoV-2 viral RNA load and dysfunction of the central nervous system.

Researchers then screened a cohort of 323 patients admitted to the emergency room between Feb. 13, 2020, and Aug. 15, 2022, categorized by whether they had mild, moderate, severe, critical, or lethal COVID-19. They found that the respiratory rate increased in survivors but decreased in non-survivors of critical COVID-19. These results suggest SARS-CoV-2 induces vagus nerve inflammation followed by autonomic dysfunction (respiratory rate decrease), which “contributes to critical disease courses and might contribute to dysautonomia observed in long COVID.”

Responding to the study, microbiologist Amy Proal of PolyBio Research Foundation wrote on X, “Because the vagus nerve is an essential component of the #autonomic nervous system and regulates body functions such as heart rate, digestion, and respiratory rate, direct infection of the nerve by SARS-CoV-2 may contribute to related symptoms.” She added, “The findings beg the question: Could persistent SARS-CoV-2 infection of the vagus nerve contribute to dysautonomia in #LongCovid?”

What Is Dysautonomia?

Nearly 1 in 5 people in the United States continue to experience unexplained symptoms of long COVID after their infection has ended, with as many as 66 percent of patients suffering from moderate to severe dysfunction of the ANS known as dysautonomia.

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Dysautonomia is a disorder of the ANS, a part of the central nervous system that controls vital involuntary functions such as breathing, heart rate, blood pressure, digestion, skin and body temperature regulation, salivating, hormonal and bladder function, and sexual function. The ANS also plays a role in the acute “fight or flight” stress response and sends messages to and from internal organs.

Dysautonomia causes the ANS—which consists of the sympathetic, parasympathetic, and enteric nervous systems—to malfunction, either through an inability to perform its tasks or by causing too much activity, resulting in high blood pressure or a rapid heart rate. The condition can be confined to the arms and legs or spread throughout the entire body. It can be severe or mild, and may be reversible or worsen over time.

Postural orthostatic tachycardia syndrome (POTS) is a common form of dysautonomia that has increased since the COVID-19 pandemic began and has been reported by those with long COVID and in those following COVID-19 vaccination.

Symptoms of POTS include but aren’t limited to lightheadedness, difficulty thinking or concentrating, severe and long-lasting fatigue, intolerance to exercise, blurred vision, low blood pressure, heart palpitations, tremors, and nausea.

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Since the rollout of COVID-19 vaccines, 801 cases of POTS were reported to the Vaccine Adverse Events Reporting System as of July 28. This includes 597 cases attributed to Pfizer and 171 cases to Moderna.

Treatments for Dysautonomia

Therapeutic treatment options for autonomic dysfunction in the medical community are aimed at symptom management and avoiding triggers using pharmaceutical drugs and nonpharmacologic measures.

Cardiovascular Dysautonomia

For dysautonomia affecting the cardiovascular system, a 2022 study in Frontiers in Neurology recommended the following:

• Drink water before getting up in the morning.
• Elevate the head during sleep.
• Monitor water and salt intake.
• Use compression garments.
• Engage in progressive aerobic exercise.
• Avoid situations that worsen symptoms such as sleep deprivation, heat exposure, large meals, and alcohol consumption.

To prevent fainting, perform physical movements such as crossing the legs, tensing muscles, and squatting. For those who don’t respond to nonpharmacological options, medications that inhibit heart rate, vasoconstrictors, sympatholytic drugs, and volume expanders, including intravenous fluids may be prescribed.

POTS

The Frontiers study stated that people with POTS may benefit from fluid replacement and one or two additional teaspoons of salt per day, avoiding caffeine and alcohol, and avoiding anything that worsens symptoms such as prolonged standing, hot environments, and dehydration. Moving carefully from a lying or sitting position to standing is advised.

Medical treatments may include beta blockers, drugs for orthostatic hypotension to increase blood pressure, propranolol to reduce heart rate, and pyridostigmine—typically used to treat people with muscle weakness. However, the effectiveness of drug therapy is modest, and some drugs aren’t well tolerated.

Dysautonomia Associated With Long COVID or Post-Vaccine Syndromes

The Frontline COVID-19 Critical Care Alliance (FLCCC) has played a major role in treating long COVID and post-vaccine injuries, including people with dysautonomia.

Many long COVID patients are vaccinated, making it difficult to determine whether their prolonged symptoms are due to COVID-19 or vaccine injury. Regardless, both are manifestations of “spike protein-related disease” and share a significant overlap in symptoms, pathogenesis, and treatment, according to the FLCCC.

The FLCCC has developed protocols for people with long COVID and those experiencing post-vaccine injuries, including POTS.

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They recommend that patients undergo a series of initial tests to determine whether they have long COVID, and a chest scan for those who have respiratory symptoms to differentiate between long COVID and post-vaccine syndrome.

Protocols are geared toward either long COVID (pdf) or post-vaccine injuries (pdf)—including dysautonomia disorders such as POTS—exercised under the care of a practitioner.

Other Dysautonomia Treatments

Another study published in Frontiers Neurology found that noninvasive neuromodulation using ultrasound and other techniques may benefit patients with dysautonomia.

These noninvasive therapies were shown to alleviate musculoskeletal pain and systemic fatigue and improve cognitive and physical rehabilitation and neurological disorders.