Millions of people worldwide live with long COVID, a condition characterized by symptoms of COVID-19 and other syndromes months after the initial illness has subsided. One aspect of particular concern is its cardiovascular implications, including a rise in postural orthostatic tachycardia syndrome (POTS) and increased cardiovascular disease risk. Our latest In Conversation episode delves into this topic.
It is unclear how many people around the world live with long COVID. However, one study that is yet to undergo peer review estimates that as of August 2021, about 43% of people who tested positive for COVID-19, and more than half of those who received hospitalized care for this disease, ended up developing long COVID.
The results of a survey published in eClinicalMedicine in July 2021 indicate that long COVID causes an array of diverse symptoms that “affect multiple organ systems, with impact on functioning and ability to work.”
The authors of this paper also point out that people with long COVID experience some unexpected conditions after their initial illness, including a hard-to-diagnose syndrome known as POTS.
POTS involves a complex mix of symptoms, including lightheadedness, brain fog, fatigue, headaches, blurry vision, heart palpitations, and nausea. These symptoms are linked to either low blood pressure or high blood pressure — hypotension or hypertension, respectively — although the precise cause behind these effects remains debatable.
A study that appeared in Nature Medicine in February 2022 goes so far as to suggest that people who develop COVID-19 have an increased risk of experiencing cardiovascular problems a year after the initial disease.
According to the study authors, at 12 months post-COVID-19, people continue to have an increased risk of “cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure, and thromboembolic disease.”
What is more, they write, “The risks were evident regardless of age, race, sex, and other cardiovascular risk factors, including obesity, hypertension, diabetes, chronic kidney disease, and hyperlipidemia; they were also evident in people without any cardiovascular disease before exposure to COVID-19.”
To better understand how and why COVID-19 and long COVID have cardiovascular implications, in our latest In Conversation podcast, we have spoken with three experts and one person who continues to navigate the difficulties of living life with long COVID.
These individuals are:
- Angela Meriquez Vázquez, Body Politic president and long COVID patient
- Dr. Lesley Kavi, trustee and chair of PoTS UK and visiting professor at Birmingham City University, United Kingdom
- Dr. Artur Fedorowski, associate professor of cardiovascular medicine at the Karolinska Institute and Karolinska University Hospital in Stockholm, Sweden
- Dr. Tae Chung, assistant professor of physical medicine and rehabilitation at Johns Hopkins Medicine and director of the Johns Hopkins POTS Program
According to Dr. Fedorowski, “somewhere between 1% and 10% of individuals [who contracted SARS-CoV-2] will develop all these [cardiovascular] complications, [such as] myocarditis, pericarditis, and even blood clots building in [the] arteries.”
The difficulty in treating these cases, moreover, is [because] the cardiovascular impact can be difficult to pinpoint at first.
“We are talking about very small blood clots in very small arteries — they are not so easy to detect,” said Dr. Fedorowski. “But some patients may report having blue fingers out of nowhere, just being infected a few days before. And this might be a sign of a very small, tiny blood clot in [the] peripheral blood arteries.”
The
To reach this conclusion, the study authors analyzed data from a large cohort of “153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals.”
This ongoing risk of cardiovascular issues does not apply only to adults. According to a paper in Circulation in November 2020, children can also experience acute heart failure weeks after having had a SARS-CoV-2 infection. This is likely to be an effect of long COVID in children, which is also under investigation.
However, the syndrome that has most puzzled scientists regarding its association with long COVID is POTS.
The medical community generally describes POTS, the syndrome that affects more and more people with long COVID, as a dysautonomic phenomenon — that is, something that affects the autonomic nervous system.
The autonomic nervous system is the body’s “autopilot mode,” which controls key bodily functions, such as heart rate, breathing, and digestion.
POTS is one of several forms of dysautonomia, alongside neurocardiogenic syncope, which involves frequent fainting spells and multiple system atrophy, a rare and fatal condition that leads to rapid systemic deterioration.
The symptoms of POTS are as numerous as they are varied, ranging from lightheadedness upon standing up from a seated position to tachycardia (an abnormally rapid heart rate), shortness of breath, and digestive symptoms.
This heterogeneity of symptoms can make POTS difficult to diagnose. Doctors often mistake it for an
“The problem with POTS is that it seems to be not only a cardiovascular problem — [a] heart and vessel problem — [but also] a problem of your nervous system, sometimes on your gastrointestinal system,” Dr. Fedorowski explained.
“And in the end, we call it ‘dysautonomia,’ as it seems [to be] about your autonomic nervous system, which controls all your autonomic functions […]. And as the autonomic nervous system controls, first of all, your circulatory system, the main symptoms that you feel are from the circulatory or from your heart palpitations or blood pressure instability — you don’t feel good when you stand up, and so on. But the problems are a little bit diffused,” he noted, pointing out that even top specialists may find it hard to diagnose POTS correctly.
Ms. Meriquez Vázquez described her experience of POTS as a life altering syndrome, and she confirmed the similarity between symptoms of POTS and those of a panic attack:
“[M]y POTS started as very severe adrenaline rushes along with a racing heart, especially when I was standing — I would get so nauseated and dizzy. From all of the adrenaline, it felt like a panic attack, but it would come out of nowhere.”
Why does adrenaline, or epinephrine, play a role? Dr. Kavi explained that “the sympathetic nervous system is the fight-or-flight system, and that’s where the adrenaline […] — noradrenaline — comes in.”
“The parasympathetic system is the rest-and-digest system. And for us to function normally, we have to have a balance between the two — a sort of equilibrium. And it’s when that equilibrium gets disrupted, and one or [the other] is overpowering that people develop problems,” she explained.
The mechanisms behind POTS remain unclear, but ongoing research is searching for the likeliest explanations.
A study published in February 2022 in Cells found that people with POTS have platelet storage pool deficiency, a phenomenon linked to symptoms such as frequent nosebleeds, dysmenorrhea, easy bruising, and anemia.
It also showed that people with POTS have elevated inflammatory biomarkers, all of which may suggest a state of chronic inflammation.
“[T]he data provided [in this study] suggest that POTS is a mixed inflammatory pattern disease,” the authors conclude.
Although more and more media content has started looking at POTS as a long-term effect of SARS-CoV-2 infections, POTS itself is not a newly emerged syndrome.
According to data that the nonprofit organization Dysautonomia International cited well before the pandemic, an estimated 1–3 million people in the U.S. had POTS.
Although it is unclear how many more people are seeking care in the aftermath of COVID-19 than they were pre-pandemic,
Dr. Fedorowski also told us that he and his colleagues at the Karolinska University Hospital in Sweden have been seeing an influx of people with long COVID whom doctors have referred for POTS treatment:
“We experience a huge inflow of new referrals from different parts of the region of Stockholm, meaning that in the Stockholm area, [where] we have around 2.5 million citizens, […] from [that] whole area, we are getting referrals from primary care doctors [and] from other specialists from other hospitals regarding people who developed what we call ‘long COVID’ or ‘post-COVID syndrome.’ The main reason they are sent to us is that [here] is quite [a] high clinical suspicion of POTS — postural orthostatic tachycardia syndrome.”
According to Dr. Fedorowski, at almost 2 years into the COVID-19 pandemic, the number of referrals for POTS rehabilitation “has doubled or tripled.”
Dr. Chung made a similar observation about the Johns Hopkins POTS Program, saying that he and his colleagues “have [had] at least twice or three times more referrals” at their clinic since the start of the pandemic, compared with pre-pandemic numbers.
And Dr. Kavi told us that the situation is the same in the U.K.: “Here, the feedback that I’m getting from the clinicians that we work with — who run POTS services and secondary care […] — [is] that they’re noticing a significant increase in their referrals. And, of course, that means that their waiting lists are getting longer as well.”
Current data indicate that the people who most commonly receive a diagnosis of POTS in long COVID are young females.
However, both Dr. Fedorowski and Dr. Chung noted that there is a slight difference in the demographics of people presenting with POTS before the COVID-19 pandemic and those who have POTS associated with long COVID.
According to the researchers, pre-pandemic, most people with POTS tended to be in their teens or early 20s, while people with long-COVID-associated POTS tend to be in their 30s, 40s, and 50s.
Dr. Fedorowski speculated that the high levels of stress that women in these demographics often encounter, perhaps due to persistent issues of gender inequality in the home and workplace, may play a role.
“A lot of younger women […] get affected by POTS as a consequence of COVID-19,” Dr. Fedorowski told Medical News Today. “And if you talk to them […], then you will see a picture of a woman who is working very hard, having [a] family, taking care of children, and trying to reach some higher position in […] society; or [there] are the women who are very much stressed by feeling that they are not good enough.”
During the pandemic, for instance, women have
However, reflecting on the shift in POTS demographics outlined by Drs Chung and Fedorowski, Dr. Kavi wondered whether “it’s a real increase in older people having POTS [after COVID-19] or whether it’s just not being picked up in younger people” since POTS is often not given due consideration as a possible diagnosis.
“In terms of pediatricians and [family doctors], for example, they often don’t think about [POTS as a possible diagnosis], and then there’s very little, almost nothing in the way of services for people in the U.K. with POTS that are under the age of 16, so I just don’t know whether it’s there and we’re missing it or it’s not [been] there [previously].”
– Dr. Lesley Kavi
Ms Vàzquez also wondered whether more people with long COVID are now receiving POTS diagnoses not because they have newly developed the syndrome after becoming ill with COVID-19, but because their existing POTS symptoms have worsened in the aftermath.
In their online support group, she told us, people are “often reflecting on how they may have had signs of autonomic dysfunction prior to getting sick [with COVID-19].”
Research on POTS conducted before the COVID-19 pandemic further indicates that the syndrome can be associated with various chronic conditions, including diabetes, sarcoidosis, and lupus, as well as with aggressive treatments, such as chemotherapy.
There is also some suggestion that POTS can develop following a viral illness and that sometimes genetic factors may be at play.
According to PoTS UK, the syndrome can have associations with inherited conditions, such as hypermobility spectrum disorder and hypermobile Ehlers-Danlos Syndrome.
POTS also has associations with
Although POTS is an incurable condition, some medical interventions can improve its management. A mix of appropriate medication, physical therapy, and some lifestyle or behavioral interventions can help, according to the Johns Hopkins POTS Program.
Ms. Meriquez Vázquez noted that she has had to modify some of her habits to make her symptoms more manageable.
“I have to keep my blood pressure up with salt and a lot of water,” she said. “So, I take salt pills throughout the day to keep my blood pressure even. But one of the long standing symptoms that I’m still dealing with is increased migraines. So the longer I spend upright during the day, the more likely [it is] I’ll end the day with a pretty severe migraine,” she explained.
Dr. Kavi also advised an increased salt intake, as well as some other lifestyle interventions:
“[I] encourage patients to have increased salt if it’s not contraindicated and increased fluid [consumption]; compression clothing can [also] be helpful. Some people find that dietary measures, such as avoiding very heavy meals [and] refined carbohydrates, are useful. […] You can use postural maneuvers to prevent pre-syncope and fainting, such as activating skeletal muscle[s], and [as for] exercise, we usually recommend that that’s done in a horizontal position initially, and often starting at a low level.”
Exercise, however, can pose a crucial difficulty, as Ms. Meriquez Vázquez told us. “Because I […] had exercise intolerance, which to me means it’s immediately hard to exercise, […] my heart rate would skyrocket, [and] I’d get really short of breath and a little dizzy and nauseated,” she pointed out.
“[T]hen there’s […] my post-exertional malaise, so even as I got better, I would be able to exercise, and then my symptoms would flare for several days after exercise,” she added.
“So I think it’s really important, and I have been working with my doctors to help me […] manage both improving my exercise tolerance [and] finding a level of movement and energy expenditure that doesn’t crash me over the hours and days after exercise.”
– Angela Meriquez Vázquez
Although physical therapy can be tricky because, like Ms. Meriquez Vázquez, many people with POTS find that exercise worsens their symptoms, researchers continue to investigate the best ways to balance rest and physical activity.
At the Karolinska University Hospital, said Dr. Fedorowski, “we treat our patients with drugs that regulate heart rate, we treat our patients with drugs that act on the vessels and increase blood pressure in those who have low blood pressure and have difficulty standing up.”
One case published in BMJ Case Reports in June 2021 outlined the potential of using ivabradine, a drug that doctors typically use to treat heart failure, in the treatment of POTS.
“We are [also] using drugs that are working on different receptors, like muscarinic receptors, to counteract muscle weakness,” said Dr. Fedorowski. “We are trying out drugs against brain fog [that] otherwise have been used to fight or to treat ADHD [attention deficit hyperactivity disorder].”
The research on long-COVID-associated POTS and the best treatment methods for this syndrome continues. There is hope that, in the not-too-distant future, targeted medication may solve what has seemed unsolvable so far.
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