What is the clinical evidence from this study?

Study design: Case-Control. Population: Long COVID (n=26). Intervention: Long COVID vs. Recovered from COVID-19 without ongoing symptoms. Primary outcome: COMPASS 31 total score (p=0.003).

What does this research mean for the field?

Although individuals with Long COVID frequently experience autonomic symptoms and elevated heart rates during tilt table testing, most do not meet diagnostic criteria for clinically abnormal hemodynamic responses. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To characterize autonomic symptom burden and hemodynamic responses to positional changes in individuals with Long COVID compared to recovered controls.

October 24, 2025PLoS ONEOpen Access

Case-control study of autonomic symptoms in the setting of Long COVID with tilt table testing

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Key result

Long COVID is linked to a ~23-point higher autonomic symptom burden versus recovered controls.

P=0.003
n=26

Why the study?

Autonomic symptoms and orthostatic syndromes have been reported in Long COVID, but few studies have characterized findings using head up tilt table testing.

Does head-up tilt table testing reveal objective hemodynamic abnormalities corresponding to autonomic symptoms in individuals with Long COVID compared to recovered controls?

Key Points

To characterize autonomic symptom burden and hemodynamic responses to positional changes in individuals with Long COVID compared to recovered controls.
Conducted a case-control study including 26 participants (16 with Long COVID and 10 recovered comparators; median age 56 years, 50% female) evaluated at a median of 25 months after initial SARS-CoV-2 infection.
Assessed autonomic symptoms using the Composite Autonomic Symptom Scale 31 (COMPASS 31) instrument and performed head-up tilt table testing for 30 minutes at 70 degrees.
COMPASS 31 scores were significantly higher in the Long COVID group than among recovered comparators (median 30.5 vs 8, p = 0.003), and symptoms arose during tilt in 10 (63%) with Long COVID versus 0 (0%) controls (p = 0.003).
Average heart rate was 8 beats per minute higher throughout tilt among participants with Long COVID (95% CI 1.1 to 14.4; p = 0.02), whereas blood pressure did not differ significantly between groups.
Three (19%) participants with Long COVID demonstrated clinically abnormal responses (one orthostatic hypotension, one delayed orthostatic hypotension, and one cardioinhibitory/vasovagal presyncope), but zero participants met diagnostic criteria for POTS.

Study Design

Type

Case-Control (n=26)

Structured PICO

Does head-up tilt table testing reveal objective hemodynamic abnormalities corresponding to autonomic symptoms in individuals with Long COVID compared to recovered controls?

Population

26 adults (median age 56, 50% female) evaluated a median of 25 months after initial COVID-19 infection, comprising 16 individuals with Long COVID and 10 recovered comparators.

Exposure

Head-up tilt table testing (HUTT) for 30 minutes at 70 degrees (unmedicated) and assessment of autonomic symptoms using the COMPASS 31 instrument.

Comparator

Age- and sex-matched recovered comparators without Long COVID or persistent symptoms, undergoing the exact same HUTT and COMPASS 31 assessments.

Outcome

Autonomic function assessed primarily by COMPASS 31 symptom score and hemodynamic responses (heart rate and blood pressure) during head-up tilt table testing.patient reported

Main Result

Absolute Event Rate: 30.5% vs 8%

p-value: p=0.003

Despite experiencing frequent orthostatic symptoms and exhibiting elevated heart rates, most individuals with cardiovascular Long COVID do not meet strict diagnostic criteria for POTS during unmedicated tilt table testing.

Limitations

Small sample size and case-control design, which limits the ability to estimate prevalence.
Lack of continuous beat-to-beat blood pressure or cerebral blood flow measurement, reducing sensitivity for detecting hemodynamic changes.
Lack of comprehensive autonomic function testing using quantitative sudomotor axon reflex test, skin biopsy, or response to Valsalva maneuver or deep breathing.
Correlative data such as echocardiography, CPET, and ambulatory heart rhythm monitoring were not available for all participants.
Small sample size
Case-control design limiting ability to estimate community prevalence of Long COVID POTS
Lack of continuous beat-to-beat blood pressure or cerebral blood flow measurement
Lack of comprehensive autonomic function assessment (e.g., QSART, skin biopsy, Valsalva, deep breathing)
Correlative data such as CPET and echocardiography were not available for all participants

Implication

Supports orthostatic symptom evaluation in Long COVID; leaves open whether tilt testing identifies treatable autonomic dysfunction.

Abstract

BACKGROUND: Autonomic symptoms and orthostatic syndromes have been reported in Long COVID, but few studies have characterized findings using head up tilt table testing. OBJECTIVE: To characterize autonomic responses to positional changes among individuals with Long COVID. METHODS: We assessed autonomic symptoms using the Composite Autonomic Symptom Scale 31 (COMPASS 31) instrument and performed head up tilt table testing for 30 minutes at 70 degrees among individuals with Long COVID and recovered comparators. RESULTS: We included 26 participants (median age 56 years, 50% female median 25 months after first COVID): 16 with Long COVID and 10 recovered comparators. COMPASS 31 scores (0-100, higher is worse) were higher among those with Long COVID (median 30.5 vs 8, p = 0.003). Heart rate was 8 beats per minutes higher throughout tilt among those with Long COVID (95% CI 1.1 to 14.4; p = 0.02); there were no differences in blood pressure. Ten (63%) with Long COVID had symptoms during tilt compared to none among recovered participants (p = 0.003). Three (19%) with Long COVID had clinically abnormal findings: one each with orthostatic hypotension, and delayed orthostatic hypotension, and cardioinhibitory/vasovagal presyncope. CONCLUSIONS: Among those with chronic autonomic symptoms in the setting of Long COVID, symptoms were common during tilt testing, and heart rate was increased, but most did not meet diagnostic criteria for a clinically abnormal hemodynamic response. Further research into mechanisms of autonomic symptoms in Long COVID is urgently needed.

Discussion

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Cite This Study

Durstenfeld et al. (2025) conducted a case-control in Long COVID (n=26). Long COVID vs. Recovered from COVID-19 without ongoing symptoms was evaluated on COMPASS 31 total score (p=0.003). Long COVID was associated with a higher autonomic symptom burden (median COMPASS 31 score 30.5 vs 8) and a higher average heart rate during tilt testing compared to recovered individuals.

synapsesocial.com/papers/6a61dc586e9a4038e37d8fc4 https://doi.org/10.1371/journal.pone.0335218

Topics

COVID-19 cardiovascular

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Implication

Supports orthostatic symptom evaluation in Long COVID; leaves open whether tilt testing identifies treatable autonomic dysfunction.

Case-control study of autonomic symptoms in the setting of Long COVID with tilt table testing

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

Case-control study of autonomic symptoms in the setting of Long COVID with tilt table testing

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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