Safety of Cardiopulmonary Exercise Testing in Patients with Severe Post- COVID-19 Condition: A Matched Case- Control Study
Abstract
Patients severely affected by post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) exhibit reduced physical capacity, hyperventilation, and a high susceptibility to post-exertional malaise (PEM).
Cardiopulmonary exercise testing (CPET) is considered the gold standard for objectively assessing physical capacity and for exploring underlying physiological limitations. However, evidence regarding the safety and PEM-associated symptoms following CPET remains limited. This study aims to objectively assess physical capacity using CPET, and to systematically investigate changes in PEM-associated symptom duration and severity before and after CPET.
18 PCC patients and 18 healthy controls (matched for sex, age, and body-mass-index) completed a single maximal symptom-limited CPET on a bicycle ergometer. Ten PEM-specific symptoms were assessed daily for 7 days before and 14 days after CPET (scale 0-10). For clinical characterization, the Canadian Consensus Criteria (CCC), Bell Disability Scale, and DePaul Symptom Questionnaire Short-Form-PEM (DSQ-PEM) questionnaires were completed once before the CPET.
Among PCC patients, 61% fulfilled ME/CFS criteria, 67% screened positive for DSQ-PEM, and the mean Bell-Score was 37.8 ± 19.3.
Physical capacity was markedly reduced compared with healthy controls (Peak power output: 1.1 vs. 2.4 W/kg, p < 0.001; VO 2peak 16.0 vs. 26.5 mL/min/kg; p < 0.001).
In the PCC group, a significant increase in mean symptom severity was observed across all measured symptoms from baseline to the acute period (1-3 days after the CPET; Δ = 0.56, p = 0.002) but after 4-7 days, levels returned to baseline. Two out of ten symptoms increased significantly after the CPET: general fatigue (Δ = 0.99, p = 0.018) and joint pain (Δ = 0.69, p = 0.036). However, after 4 to 7 days no significant differences remained.
No significant group-by-timepoint interaction was found when stratifying PCC patients by DSQ-PEM status (p = 0.187), Bell-Scores (≤30 vs. >30, p = 0.276), or ME/CFS status (p = 0.523). Severely affected PCC patients showed markedly reduced physical capacity compared with matched controls.
A single maximal but symptom-limited CPET induced only a transient, clinically non-relevant symptom increase (1-3 days) without prolonged exacerbation. Furthermore, the results of the CPET can be used to provide individualized objective cut-off values aimed at minimizing PEM during exercise therapy and/or activities of daily living.
Trial registration: DRKS, DRKS00032394. Registered 28 July 2023, https://drks.de/search/de/trial/DRKS00032394
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Weber, Vincent; Tomaskovic, Aleksandar; Ochmann, David T.; Hillen, Barlo; Zentgraf, Severin; Enger, Mirjam S.; Lachtermann, Ella; Neuberger, Elmo W. I.; Simon, Perikles
Abstract
Patients severely affected by post-COVID-19 condition (PCC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) exhibit reduced physical capacity, hyperventilation, and a high susceptibility to post-exertional malaise (PEM).
Cardiopulmonary exercise testing (CPET) is considered the gold standard for objectively assessing physical capacity and for exploring underlying physiological limitations. However, evidence regarding the safety and PEM-associated symptoms following CPET remains limited. This study aims to objectively assess physical capacity using CPET, and to systematically investigate changes in PEM-associated symptom duration and severity before and after CPET.
18 PCC patients and 18 healthy controls (matched for sex, age, and body-mass-index) completed a single maximal symptom-limited CPET on a bicycle ergometer. Ten PEM-specific symptoms were assessed daily for 7 days before and 14 days after CPET (scale 0-10). For clinical characterization, the Canadian Consensus Criteria (CCC), Bell Disability Scale, and DePaul Symptom Questionnaire Short-Form-PEM (DSQ-PEM) questionnaires were completed once before the CPET.
Among PCC patients, 61% fulfilled ME/CFS criteria, 67% screened positive for DSQ-PEM, and the mean Bell-Score was 37.8 ± 19.3.
Physical capacity was markedly reduced compared with healthy controls (Peak power output: 1.1 vs. 2.4 W/kg, p < 0.001; VO 2peak 16.0 vs. 26.5 mL/min/kg; p < 0.001).
In the PCC group, a significant increase in mean symptom severity was observed across all measured symptoms from baseline to the acute period (1-3 days after the CPET; Δ = 0.56, p = 0.002) but after 4-7 days, levels returned to baseline. Two out of ten symptoms increased significantly after the CPET: general fatigue (Δ = 0.99, p = 0.018) and joint pain (Δ = 0.69, p = 0.036). However, after 4 to 7 days no significant differences remained.
No significant group-by-timepoint interaction was found when stratifying PCC patients by DSQ-PEM status (p = 0.187), Bell-Scores (≤30 vs. >30, p = 0.276), or ME/CFS status (p = 0.523). Severely affected PCC patients showed markedly reduced physical capacity compared with matched controls.
A single maximal but symptom-limited CPET induced only a transient, clinically non-relevant symptom increase (1-3 days) without prolonged exacerbation. Furthermore, the results of the CPET can be used to provide individualized objective cut-off values aimed at minimizing PEM during exercise therapy and/or activities of daily living.
Trial registration: DRKS, DRKS00032394. Registered 28 July 2023, https://drks.de/search/de/trial/DRKS00032394
Web | DOI | PDF | Research Square | Preprint
