Experts say POTS should be included in the diagnostic criteria for long covid and considered for regular autonomic assessment in patients with ongoing post-viral symptoms.
Almost two-thirds of long covid patients meet the diagnostic criteria for postural orthostatic tachycardia syndrome (POTS), according to new research. Researchers say better tests are needed to confirm whether autoimmunity plays a role.
POTS affects approximately 800,000 Australians, affecting automatic body functions including heart rate, breathing and digestion.
The study, conducted by Adelaide University in partnership with SAHMRI and published in the Journal of the American Heart Association, is likely the first to examine autonomic symptoms, heart rate response, inflammatory markers, and autoantibodies in people with long covid, POTS, and healthy volunteers.
Participants lay supine for five minutes, then performed an unassisted active stand test lasting 10 minutes. The change in heart rate from supine to peak standing was calculated as the primary autonomic variable, and their orthostatic symptoms were reported verbally.
Upon standing, participants’ average heart rates rose by 46 beats per minute in the POTS group and 35 beats per minute in the long covid group, compared with just 13 beats per minute in healthy volunteers.
Recruitment occurred between August 2021 and December 2022 and comprised 67 women, predominantly white, aged 18 years and older.
Researchers found those with POTS and long covid were “clinically indistinguishable” in their impact on patients’ quality of life.
However, the POTS cohort exhibited significantly worse gastrointestinal, bladder and pupillomotor symptoms than the long covid group.
Researchers theorised this could reflect POTS involving more widespread, chronic autonomic dysfunction than long covid, or simply that the POTS group had been ill for longer.
They also proposed that longer illness duration may lead to acclimatisation, causing patients to adjust their expectations and coping strategies over time, which could explain why POTS patients reported similar overall distress despite worse physiological dysfunction in those domains.
Almost six in 10 (58.3%) of long covid participants reported being unable to return to work following their infection, despite 87.5% of people being employed full-time beforehand, while just 4.2% of participants with POTS reported undertaking full-time work or education.
Lead researcher Dr Marie-Claire Seeley from the Rosemary Bryant AO Research Centre at Adelaide University said the first two years of having POTS were often the most severe; however, this was when most were trying to obtain a diagnosis.
Without public healthcare support, Dr Seeley said the impact of POTS was often even more severe for rural patients, those from lower socioeconomic backgrounds and linguistically diverse patients, where access to specialists was often available in only a few urban centres.
She called for government-funded access to outpatient rehabilitation programs for POTS, noting that none currently exist.
“Our biggest problem is finance. There has never been any serious money put into POTS research,” she said.
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Dr Seeley told The Medical Republic further research involving 200 long covid patients had been undertaken, but the data had not yet been published.
“It is possible that in using the active stand test, a few patients who actually have POTS might be missed,” she said.
But in cases of clinical suspicion, patients should be retested, she said.
“There’s no reason to make patients wait months on end for a test that doesn’t tell us anything different than what an active stand test can tell us,” she said.
Approximately 83% of the cohort exhibited clinically meaningful autonomic disturbance, suggestive of underlying autonomic dysfunction, even if they did not meet the full POTS criteria.
Prior research has proposed that autoantibodies might drive POTS and long covid by overstimulating the autonomic nervous system.
However, blood tests found no meaningful differences in autoantibody levels that activate the α1- and β1-adrenergic receptors involved in heart rate and blood vessel constriction across the POTS, long covid and healthy groups.
When researchers used a statistical model to determine which biomarkers best predicted POTS, interleukin-8, a marker of inflammation, was the only biomarker independently associated with the condition, a finding researchers said warranted further investigation.
Researchers emphasised the need for cautious interpretation, viewing it as “hypothesis-generating” and requiring replication in larger longitudinal studies.
Dr Michaelia Verbeek, a GP specialising in POTS and long covid, said in her clinical experience, covid was a significant trigger for the onset of POTS or a “substantial flare” in patients’ symptoms.
“I think it’s really important that we change the perception within the medical community that POTS is inherently difficult to diagnose or recognise,” she said.
Despite POTS diagnoses being relatively straightforward, Dr Verbeek told TMR that symptoms may often be overlooked because of a clinician’s low index of suspicion, time constraints during GP consultations, and a lack of awareness that symptoms can fluctuate considerably day-to-day.
“Testing needs to be performed probably several times and under the appropriate conditions, so that we’re looking at the potential medication interactions or whether the patient is fluid and salt-loaded already,” she said.
She also called for a low threshold for POTS screening in any patient experiencing persistent fatigue, brain fog, exercise intolerance, long covid, or symptoms labelled as anxiety.
When asked about the 10-minute standing test, she said it would be a “very feasible assessment”.
“There are simply too many patients for every suspected case of POTS to be referred to a specialist,” she said.
“It’s unlikely that the GP could do it in their 15-minute consult, because these tests can take a good 20 minutes, with appropriate lying down beforehand,” she said.
Rather, having a Malmö screening questionnaire, a 12-item self-rating questionnaire, that patients could complete at home and educating nurses on how to perform the sit-to-stand test appropriately would allow GPs to review the results and begin basic management, she told TMR.
“We need more GPs to be aware of [POTS] and help support [treatment], because we don’t have enough specialists, including GP specialists like myself,” Dr Verbeek said.
While POTS most often affects younger women, Dr Verbeek said GPs should also monitor for symptoms in mothers of neurodivergent children.
“We can explain fatigue and anxiety due to a lot of contextual factors, like being a busy mum, not sleeping well, caring for children,” she said.
Read the full study here.
