Use of Cardiopulmonary Exercise Testing to Evaluate Long COVID-19 Symptoms in Adults - A Systematic Review and Meta-analysis, 2022, Durstenfeld et al

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Mij

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Preprint

Abstract

Importance: Reduced exercise capacity is commonly reported among individuals with Long COVID (LC). Cardiopulmonary exercise testing (CPET) is the gold-standard to measure exercise capacity to identify causes of exertional intolerance.

Objectives: To estimate the effect of SARS-CoV-2 infection on exercise capacity including those with and without LC symptoms and to characterize physiologic patterns of limitations to elucidate possible mechanisms of LC.

Data Sources: We searched PubMed, EMBASE, and Web of Science, preprint severs, conference abstracts, and cited references in December 2021 and again in May 2022.

Study Selection: We included studies of adults with SARS-CoV-2 infection at least three months prior that included CPET measured peak VO2. 3,523 studies were screened independently by two blinded reviewers; 72 (2.2%) were selected for full-text review and 36 (1.2%) met the inclusion criteria; we identified 3 additional studies from preprint servers.

Data Extraction and Synthesis: Data extraction was done by two independent reviewers according to PRISMA guidelines. Data were pooled with random-effects models. Main Outcomes and Measures: A priori primary outcomes were differences in peak VO2 (in ml/kg/min) among those with and without SARS-CoV-2 infection and LC.

Results: We identified 39 studies that performed CPET on 2,209 individuals 3-18 months after SARS-CoV-2 infection, including 944 individuals with LC symptoms and 246 SARS-CoV-2 uninfected controls. Most were case-series of individuals with LC or post-hospitalization cohorts. By meta-analysis of 9 studies including 404 infected individuals, peak VO2 was 7.4 ml/kg/min (95%CI 3.7 to 11.0) lower among infected versus uninfected individuals. A high degree of heterogeneity was attributable to patient and control selection, and these studies mostly included previously hospitalized, persistently symptomatic individuals. Based on meta-analysis of 9 studies with 464 individuals with LC, peak VO2 was 4.9 ml/kg/min (95%CI 3.4 to 6.4) lower compared to those without symptoms. Deconditioning was common, but dysfunctional breathing, chronotropic incompetence, and abnormal oxygen extraction were also described.

Conclusions and Relevance: These studies suggest that exercise capacity is reduced after SARS-CoV-2 infection especially among those hospitalized for acute COVID-19 and individuals with LC. Mechanisms for exertional intolerance besides deconditioning may be multifactorial or related to underlying autonomic dysfunction.


https://www.medrxiv.org/content/10.1101/2022.06.15.22276458v1
 
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A useful review, but from an ME perspective I would like to know more about (note. Not fully with it so did struggle reading the full article):
  1. Patient heterogeneity? Though mentioning the issue of potential heterogeneity in the patient populations I could not find discussion of the potential distinctions between those whose Long Covid reflected one off structural damage arising during the acute viral infection stage and those with an ongoing disease/illness process. You might expect someone with only lung damage to have different issues to someone with ME/CFS like symptoms. Also though the papers reviewed included patients at least three months after the acute illness, only one study looked at patient as long as a year after. This means they are unable to distinguish between transient post viral issues and ongoing conditions (this will be particularly important for research looking at rehabilitation).
  2. Ongoing disease process versus one off damage? As mentioned the studies reviewed looked at patients relatively soon after the acute phase, so does not enable any distinction between what is a one off result of the acute phase (eg neurological damage) and what is an ongoing process such as ME/CFS. The potentials for rehabilitation and for ongoing management may be very different for the (two?) groups.
  3. 2 day CPET? Given we see the main abnormalities in ME/CFS arising on the second day of 2 day CPET, it might be that 2 day tests would tell us more about those patients with ME/CFS like symptoms.
 

Long covid may set you back a decade in exercise gains

Scientists say that exercise intolerance should now be considered a new symptom of long Covid.

“We don’t yet know the trajectory” of long covid and exercise intolerance, he continued, or how long the condition lasts, whether it can be treated or if it may slowly resolve on its own. But the long-term goal of his and other research, he said, is to help people with long covid eventually find ways to become active again.

https://www.washingtonpost.com/wellness/2022/10/13/long-covid-exercise-symptoms
 
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Post copied from
Long Covid in the media and social media 2022 (there is some discussion there)

Cardiopulmonary Tests in Long COVID Offer Some Clues, Pose More Questions

any patients with symptoms of long COVID have reduced exercise capacity, which if better understood might be helpful in managing their treatment, according to a systematic review and meta-analysis of nearly 40 studies.

The analysis was conducted by researchers studying volunteers as part of the Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort.

“One of the things we were noticing was that participants were reporting reduced exercise capacity, especially those who had other long COVID symptoms,” said Matthew S. Durstenfeld, MD (University of California, San Francisco at Zuckerberg San Francisco General Hospital, CA). “As we were starting to do our own cardiopulmonary exercise test, we wanted to see what other people had done and what they had found.”

In a paper published October 12, 2022, in JAMA Network Open, his group reports that compared with people without long COVID, those with ongoing symptoms had an exercise capacity that was reduced an average of 5 mL/kg/min on cardiopulmonary exercise testing (CPET).

“This finding really does validate that we can objectively measure something in long COVID, at least in comparison to people who don't have long COVID,” Durstenfeld told TCTMD. The researchers believe that studying the trajectory of exercise capacity in these individuals could help with the design of therapies to address various aspects of long COVID.
Click to expand...

Mancini, who led one of the studies included in the meta-analysis, pointed out that the new paper doesn’t clarify much, since not all of the studies included were peer reviewed while others included both hospitalized and nonhospitalized patients, had varied definitions of long COVID, and by turns excluded or included patients with abnormal chest X-rays and echocardiograms.

“It’s a mixed bag,” she said. “The variability in the exercise test is definitely a problem in this meta-analysis and doing similar exercise testing would be helpful for future comparisons.”
Click to expand...
Chronic Fatigue Overlap
Long COVID researchers also are looking to chronic fatigue for some answers, since some studies, like the one by Mancini, show that up to 50% of long COVID patients have symptoms consistent with myalgic encephalomyelitis/chronic fatigue. The two syndromes appear to have considerable overlap, Mancini added, with shared symptoms like reduced peak VO2 and chronotropic incompetence.

“But in terms of can we look at chronic fatigue and apply treatments to COVID, the problem is that there's no good treatment for chronic fatigue,” she said.
Click to expand...

https://www.tctmd.com/news/cardiopulmonary-tests-long-covid-offer-some-clues-pose-more-questions
 
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