Key result
Two-day 6-minute step test shows poor agreement with two-day CPET for post-exertional malaise.
Why the study?
Assessing post-exertional malaise in post COVID-19 condition is challenging because the gold-standard two-day CPET carries high cost and patient burden, prompting evaluation of the two-day 6MIST as a more accessible alternative.
Does the two-day 6MIST agree with the two-day CPET for assessing post-exertional malaise in patients with post COVID-19 condition?
Does the two-day 6MIST agree with the two-day CPET for assessing post-exertional malaise in patients with post COVID-19 condition?
The two-day 6MIST is not currently a reliable alternative to the two-day CPET for objectively assessing post-exertional malaise in post COVID-19 condition.
Background Post-Exertional Malaise (PEM) is a core symptom of post COVID-19 condition (also known as long COVID) affecting millions of people, yet assessment remains challenging. The two-day cardiopulmonary exercise test (CPET) is the current gold standard for objectifying PEM, but its cost and patient burden limit use. The two-day 6-minute incremental step test (6MIST) with wireless wearable sensors could offer a more accessible alternative. Methods This cross-over study (n = 25, one-month washout period) evaluated the level of agreement and reliability between the two-day 6MIST and the two-day CPET for assessing PEM. Each “two-day” test consisted of two identical exercise tests separated by 24 hours to capture worsening of symptoms on day 2. Objective (VO 2 peak) and subjective (fatigue, neuromuscular complaints and rated perceived exertion) PEM outcomes were collected. Subjective outcomes were measured in relation to the first exercise test of each two-day session; at 15 minutes pretest, 15 minutes posttest and 24 hours posttest, with changes analyzed as Δ1 (baseline to 15 minutes posttest) and Δ2 (15 minutes posttest to 24 hours posttest). Agreement was assessed using Bland-Altman plots and reliability through consistency Intraclass Correlation Coefficients. The study is registered in ClinicalTrials.gov (Ref: NCT06933017). Results VO 2 peak and neuromuscular complaints showed low agreement and reliability between the two tests. Rated perceived exertion showed moderate reliability at all times and fatigue showed moderate reliability for changes after 24h (Δ2). Conclusions Contrary to our hypothesis, the two-day 6MIST shows limited agreement with the two-day CPET overall. However, moderate reliability for rated perceived exertion and fatigue suggests potential for improvement with protocol refinement. Further research is needed to optimize the two-day 6MIST and to develop assessments that capture PEM both within and beyond the 24-hour period.
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Bomans et al. (2026) studied Post COVID-19 condition with post-exertional malaise (n=25). Two-day 6-minute incremental step test (6MIST) vs. Two-day cardiopulmonary exercise test (CPET) was evaluated on Agreement in change in VO2 peak between day 1 and day 2 (ICC 0.012, 95% CI -0.413 to 0.432, p=0.479). The two-day 6-minute incremental step test showed low agreement and reliability (ICC 0.012) with the two-day cardiopulmonary exercise test for assessing objective post-exertional malaise.
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