Cardiorespiratory physiology, exertional symptoms, and psychological burden in post-COVID-19 fatigue

Schaeffer, Michele R.; Cowan, Juthaporn; Milne, Kathryn M.; Puyat, Joseph H.; Voduc, Nha; Corrales–Medina, Vicente F.; Lavoie, Kim L.; Mulloy, Andrew; Chirinos, Julio A.; Abdallah, Sara J.; Guenette, Jordan A.

doi:10.1016/j.resp.2022.103898

Cited by 18 publications

(22 citation statements)

References 12 publications

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“…Deconditioning is commonly reported, perhaps because most studies predominantly included hospitalized individuals and even non-hospitalized individuals experience deconditioning after illness. 22,[80][81][82][83][84] Although we observed findings consistent with deconditioning or obesity in a few individuals (earlier anaerobic threshold, accelerated heart rate response), our findings argue against deconditioning as the primary explanation. Identifying deconditioning as a cause is challenging because it is also an effect of reduced habitual exercise among symptomatic individuals.…”

Section: Other Studies Of Pasc Using Cpetcontrasting

confidence: 50%

“…All reported lower peak VO 2 among those with symptoms despite differences in defining symptoms. 18–21, 29, 30 Most assessed mostly previously hospitalized individuals at 3-6 months after infection. These studies have not reached consistent conclusions regarding the etiology of reduced exercise capacity, which may be related to different study populations, exercise protocols and proportions with sub-maximal tests.…”

Section: Discussionmentioning

confidence: 99%

“…Two studies attributed lower peak VO 2 to inadequate augmentation of stroke volume 30 or chronotropic incompetence and poor stroke volume augmentation. 21 Others have attributed exercise limitations to ventilatory inefficiency from pulmonary vasculopathy, 18 respiratory abnormalities, 19 obesity and differences in cardiorespiratory fitness 29 and deconditioning. 20, 21…”

Section: Discussionmentioning

confidence: 99%

“…Two studies attributed lower peak Durstenfeld et al CPET, CMR, and Ambulatory Rhythm Findings >12 months after COVID-19 VO2 to inadequate augmentation of stroke volume 30 or chronotropic incompetence and poor stroke volume augmentation. 21 Others have attributed exercise limitations to ventilatory inefficiency from pulmonary vasculopathy, 18 respiratory abnormalities, 19 obesity and differences in cardiorespiratory fitness 29 and deconditioning. 20,21 Impaired oxygen extraction at the peripheral level (assessed using invasive CPET) has also been suggested to explain reduced exercise capacity among those with PASC at 11 months after infection by Singh et al 31 However, they describe stopping CPETs once RER was greater than 1.10 or heart rate was >85% predicted, which is below maximal exercise for most individuals and does not allow evaluation of chronotropic incompetence.…”

Section: Other Studies Of Pasc Using Cpetmentioning

confidence: 99%

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Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Durstenfeld

Peluso

Kaveti

et al. 2022

Preprint

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BACKGROUNDMechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring.METHODSIn the Long-Term Impact of Infection with Novel Coronavirus (LIINC) Cohort, we performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection. We used logistic and linear regression to compare those with and without cardiopulmonary symptoms (dyspnea, chest pain, palpitations) adjusting for confounders.RESULTSOne hundred twenty individuals were studied, among whom 46 participants (unselected for symptom status) had at least one advanced test performed at median 17 months (IQR 15-18). Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), smaller RV volume and stroke volume and higher extracellular volume were present among those with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/15 (87%) participants with reduced exercise capacity (<85% predicted) reported cardiopulmonary symptoms or fatigue (p=0.008). Adjusted peak VO2 was 2.7 ml/kg/min lower among those with cardiopulmonary symptoms (95%CI −6.9 to 1.5; p=0.20) or −11% predicted (95%CI −27 to 5, p=0.17). Including fatigue along with cardiopulmonary symptoms, the adjusted difference in peak VO2 was −5.9 ml/kg/min (−9.6 to −2.3; p=0.002) or −21% predicted (−35 to −7; p=0.006). Chronotropic incompetence was the primary abnormality among 9/15 with reduced peak VO2. Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Those with chronotropic incompetence had higher hsCRP, lower heart rate recovery, and lower heart rate variability suggestive of autonomic dysfunction.CONCLUSIONSReduced exercise capacity and reduced heart rate response to exercise, and hsCRP are associated with persistent cardiopulmonary symptoms more than 1 year following COVID-19. Chronic inflammation and autonomic dysfunction may underlie cardiopulmonary PASC.Clinical PerspectiveWhat is New?Impaired chronotropic response to exercise is associated with reduced exercise capacity and cardiopulmonary symptoms more than 1 year after SARS-CoV-2 infection.Findings on ambulatory rhythm monitoring point to perturbed autonomic function, while cardiac MRIfindings argue against myocardial dysfunction and myocarditis.Clinical ImplicationsCardiopulmonary testing to identify etiologies of persistent symptoms in post-acute sequalae of COVID-19 or “Long COVID” should be performed in a manner that allows for assessment of heart rate response to exercise.Therapeutic trials of antiviral, anti-inflammatory, and exercise strategies in PASC are urgently needed and should include assessment of symptoms and objective testing with cardiopulmonary exercise testing.

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Section: Other Studies Of Pasc Using Cpetcontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Other Studies Of Pasc Using Cpetmentioning

confidence: 99%

See 2 more Smart Citations

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Durstenfeld

Peluso

Kaveti

et al. 2022

Preprint

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“…In addition, psychological factors may contribute substantially to the prolonged symptoms fostering exercise intolerance [ 85 ]. Schaeffer et al [ 86 ], for instance, found lower O 2peak in patients with post-COVID-19 fatigue than in those without fatigue. This was accompanied by greater dyspnoea during exercise [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Low Cardiorespiratory Fitness Post-COVID-19: A Narrative Review

et al. 2022

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Patients recovering from COVID-19 often report symptoms of exhaustion, fatigue and dyspnoea and present with exercise intolerance persisting for months post-infection. Numerous studies investigated these sequelae and their possible underlying mechanisms using cardiopulmonary exercise testing. We aimed to provide an in-depth discussion as well as an overview of the contribution of selected organ systems to exercise intolerance based on the Wasserman gears. The gears represent the pulmonary system, cardiovascular system, and periphery/musculature and mitochondria. Thirty-two studies that examined adult patients post-COVID-19 via cardiopulmonary exercise testing were included. In 22 of 26 studies reporting cardiorespiratory fitness (herein defined as peak oxygen uptake— V O 2peak ), V O 2peak was < 90% of predicted value in patients. V O 2peak was notably below normal even in the long-term. Given the available evidence, the contribution of respiratory function to low V O 2peak seems to be only minor except for lung diffusion capacity. The prevalence of low lung diffusion capacity was high in the included studies. The cardiovascular system might contribute to low V O 2peak via subnormal cardiac output due to chronotropic incompetence and reduced stroke volume, especially in the first months post-infection. Chronotropic incompetence was similarly present in the moderate- and long-term follow-up. However, contrary findings exist. Peripheral factors such as muscle mass, strength and perfusion, mitochondrial function, or arteriovenous oxygen difference may also contribute to low V O 2peak . More data are required, however. The findings of this review do not support deconditioning as the primary mechanism of low V O 2peak post-COVID-19. Post-COVID-19 sequelae are multifaceted and require individual diagnosis and treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s40279-022-01751-7.

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Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults

et al. 2022

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ImportanceReduced exercise capacity is commonly reported among individuals with COVID-19 symptoms more than 3 months after SARS-CoV-2 infection (long COVID-19 [LC]). Cardiopulmonary exercise testing (CPET) is the criterion standard to measure exercise capacity and identify patterns of exertional intolerance.ObjectivesTo estimate the difference in exercise capacity among individuals with and without LC symptoms and characterize physiological patterns of limitations to elucidate possible mechanisms of LC.Data SourcesA search of PubMed, EMBASE, Web of Science, preprint servers, conference abstracts, and cited references was performed on December 20, 2021, and again on May 24, 2022. A preprint search of medrxiv.org, biorxiv.org, and researchsquare.com was performed on June 9, 2022.Study SelectionStudies of adults with SARS-CoV-2 infection more than 3 months earlier that included CPET-measured peak oxygen consumption (V̇o2) were screened independently by 2 blinded reviewers; 72 (2%) were selected for full-text review, and 35 (1%) met the inclusion criteria. An additional 3 studies were identified from preprint servers.Data Extraction and SynthesisData extraction was performed by 2 independent reviewers according to the PRISMA reporting guideline. Data were pooled using random-effects models.Main Outcomes and MeasuresDifference in peak V̇o2 (in mL/kg/min) among individuals with and without persistent COVID-19 symptoms more than 3 months after SARS-CoV-2 infection.ResultsA total of 38 studies were identified that performed CPET on 2160 individuals 3 to 18 months after SARS-CoV-2 infection, including 1228 with symptoms consistent with LC. Most studies were case series of individuals with LC or cross-sectional assessments within posthospitalization cohorts. Based on a meta-analysis of 9 studies including 464 individuals with LC symptoms and 359 without symptoms, the mean peak V̇o2 was −4.9 (95% CI, −6.4 to −3.4) mL/kg/min among those with symptoms with a low degree of certainty. Deconditioning and peripheral limitations (abnormal oxygen extraction) were common, but dysfunctional breathing and chronotropic incompetence were also described. The existing literature was limited by small sample sizes, selection bias, confounding, and varying symptom definitions and CPET interpretations, resulting in high risk of bias and heterogeneity.Conclusions and RelevanceThe findings of this systematic review and meta-analysis study suggest that exercise capacity was reduced more than 3 months after SARS-CoV-2 infection among individuals with symptoms consistent with LC compared with individuals without LC symptoms, with low confidence. Potential mechanisms for exertional intolerance other than deconditioning include altered autonomic function (eg, chronotropic incompetence, dysfunctional breathing), endothelial dysfunction, and muscular or mitochondrial pathology.

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Cardiorespiratory physiology, exertional symptoms, and psychological burden in post-COVID-19 fatigue

Cited by 18 publications

References 12 publications

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Low Cardiorespiratory Fitness Post-COVID-19: A Narrative Review

Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults

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