Three months after a COVID infection ruined her Thanksgiving break, 19-year-old student Hannah Harding was attending a lecture when she started shaking and sweating profusely. She glanced at her Apple Watch: her heart rate was 140 beats/min.
She felt exhausted and ran out of breath easily over the next few days. “What was usually a 15-minute walk to class ended up taking a half-hour because I had to stop completely and sit on the sidewalk,” said Harding, now 24, a film production assistant in Maplewood, New Jersey. She also had brain fog and no appetite.
While returning home for spring break, she finally received a diagnosis: postural orthostatic tachycardia syndrome (POTS), an autonomic nervous system disorder that has become exponentially more common since the pandemic, with an estimated incidence two to five times higher, particularly among young women. POTS causes symptoms such as dizziness, dizziness, and tachycardia, especially when standing, as well as shortness of breath, brain fog, fatigue, digestive problems, and heat intolerance.
“I’d been seeing POTS patients for 30 years, and suddenly we were inundated with them,” said Blair Grubb, MD, an autonomic disorders specialist and director of the cardiac electrophysiology program at the University Medical Center in Toledo, Ohio.
Driven by this influx, Grubb studied the trend in more than 65.1 million patient records worldwide. His study found a 130% increase in POTS rates, from 430 cases per month in the 2 years before March 2020 to 990 per month in the next 4 years.
Now, a disease that was largely neglected for decades – and only received a diagnostic code in late 2022 – is attracting more scientific attention than ever. As more evidence links POTS to autoimmunity, treatments are shifting from controlling symptoms to medications targeting the root cause.
Does COVID cause POTS?
Most experts agree that COVID-19 triggered the increase in diagnoses, but some say greater awareness could also be a factor. “The exact magnitude of the increase attributable specifically to COVID remains unclear,” said Stavros Stavrakis, MD, PhD, vice chief of the cardiovascular disease section at the University of Oklahoma Health Campus in Oklahoma City.
Before the pandemic, POTS often went undiagnosed or was misdiagnosed, in part due to bias and a lack of understanding of the disease. “Unfortunately, to be honest, many patients are turned away because they are women,” Grubb said.
POTS is a heterogeneous syndrome, meaning it can be triggered in different ways. Viruses are the most common trigger, followed by pregnancy, then trauma such as car accidents or surgeries. An estimated 40% of people with the disease report having had a virus before their symptoms appeared, with studies showing that infections, such as those caused by the flu and the Epstein-Barr virus, often precede its onset.
“Now the bulk of the patients we see in the clinic are post-COVID,” Grubb said. Most are also young women, although the reason is unclear. “Potential explanations include sex hormones, differences in vascular physiology and blood volume regulation, and sex-related differences in immune responses and susceptibility to autoimmunity,” Stavrakis said.
The overlap with long COVID
Hannah Harding was initially diagnosed with POTS and long COVID. “They said I developed POTS as part of long COVID, and that was basically how it manifested for me,” Harding said.
But evidence suggests that in many cases, both diagnoses describe exactly the same symptoms. Long COVID, also known as post-acute COVID-19 syndrome, is an umbrella term for any symptom that persists for more than 2 or 3 months. “For most patients with long-term illness, especially those who are disabled and have multiple symptoms, their clinical features are very similar, if not identical, to those of POTS,” said Tae Chung, MD, head of a new multidisciplinary POTS and autonomic disorders program at the Shirley Ryan AbilityLab in Chicago.
In one small study, 62.5% of participants with long COVID met formal diagnostic criteria for POTS and an additional 20.8% reported orthostatic symptoms but did not meet the full criteria.
Grubb’s team studied the immune profiles of patients who developed POTS before the pandemic compared to those with POTS long associated with COVID. “The immunology is virtually identical,” Grubb said. “So I think what happened is the same syndrome is caused by a different virus.” In other words, much of what gets labeled as “long COVID” might actually be the same postviral dysautonomia that clinicians have seen for decades, simply triggered by a new virus, Grubb said.
Research points to an autoimmune component
Historically, POTS research has been limited. “A positive consequence of the pandemic is that dysautonomia and POTS have received a level of scientific attention and funding that they never had before,” Stavrakis said.
One area of investigation has focused on POTS as an autoimmune disease caused by “molecular mimicry,” in which the immune system mistakes part of the autonomic nervous system for a virus. “It continues to attack, inflaming the nerves, which destroys the autonomic nervous system,” Chung said.
Grubb’s team published two studies identifying autoimmune factors in people with POTS. In a study of 55 POTS patients who reported having had a virus before their symptoms, 89% showed high levels of antibodies against alpha-1 adrenergic receptors — the components of the autonomic nervous system responsible for heart contractions and constriction of blood vessels.
Normally, when we are standing, vasoconstriction pushes blood toward the heart and brain. This system is weakened in POTS, so it takes longer for blood to circulate, causing symptoms such as vision loss, increased heart rate, fatigue, and brain fog.
How treatment progresses
Although studies on the autoimmune drivers of POTS have yet to be validated, some researchers are moving toward treating POTS as an autoimmune disease.
Traditional POTS treatments focus on symptom management – improving vasoconstriction and slowing heart rate through medications, compression garments, and increased salt and fluid intake. Harding takes a beta blocker to lower his heart rate and has been told to wear compression socks, drink plenty of fluids and take salt to improve blood volume and circulation. But researchers and clinicians are now investigating immune-modifying drugs that could potentially target the root of the problem.
“There are many drugs on the market that manipulate your immune system,” Chung said. “If you can actually manipulate the immune system so that it stops inflaming the nervous system, that treats it at a more fundamental level.”
Specialists like Chung prescribe these drugs off-label to some patients. “Based on this experience, a lot of people think they work pretty well,” he said. But randomized controlled studies are needed to support their widespread use.
“We’re starting studies to look at the effects of using the same medications that are used to treat rheumatologic disorders,” Grubb said. “Why reinvent the wheel? Let’s try to do what they’re doing.”
After a long history of rejection, POTS patients may finally see science catching up.
Chung reported receiving consulting fees from argenx and Regeneron Pharmaceuticals. Grubb and Stavrakis did not report any relevant disclosures.
Gn Health
