In a recent study published in the medRxiv * prepress server, researchers showed reduced exercise capacity due to persistent cardiopulmonary symptoms among coronavirus 2019 (COVID-19) survivors hospitalized for acute infection and those with COVID ( LC) long.
Study: Cardiopulmonary exertion tests to assess post-acute sequelae of COVID-19 (“COVID Long”): a systematic review and meta-analysis. Image credit: BAZA Production / Shutterstock
Fund
LC, a type of post-acute sequelae of COVID-19 (PASC), is quite common after coronavirus 2 (SARS-CoV-2) infection due to severe acute respiratory syndrome. Studies have shown that between 3 and 30% of people, including those not hospitalized and vaccinated against COVID-19, suffer from LC that can persist for at least 12 months.
Cardiopulmonary exercise tests (CPET) help in the differential diagnosis of a patient’s exercise limitations. Measure resting cardiopulmonary parameters and monitor cardiopulmonary symptoms while exercising on treadmill. Oxygen consumption measurements allow the ability to exercise to be determined, and the maximum oxygen consumption or VO2 (in ml / kg / min).
These data are clinically significant and are commonly used to diagnose dyspnea and prognosis in heart failure, lung disease, and preoperative evaluations. More importantly, CPET data help assess reduced exercise capacity among adults with and without LC. However, the association between exercise intolerance and LC and the underlying pathophysiology is uncertain.
About the study
In the present study, researchers extensively searched for research studies that used CPET to assess exercise capacity in adults who contracted SARS-CoV-2 infection at least three months earlier. The search covered the Publisher MEDLINE (PubMed), Excerpta Medica (EMBASE) and Web of Science databases; the team used keywords like SARS-CoV-2 with cardiopulmonary exertion test, CPET, CPX, CPEX, exercise capacity, VO2, anaerobic threshold, customized in the database.
The researchers collected cohort studies, case series, and baseline data from intervention studies. They first did this search on December 20, 2021, then again on May 24, 2022; however, they sought prepress until June 9, 2022. The team used REDCap for independent data extraction in duplicate. Similarly, they used Cochrane’s Quality in Prognostic Studies tool to assess study populations, the quality of CPET exercise protocols, peak VO2, and submaximal test assessments, confusion, reporting, and statistical analysis.
In addition, they performed a meta-analysis of random effects to estimate the mean difference in maximal VO2 between those with and without LC and SARS-CoV-2 infection. Patient selection and control introduced a high degree of heterogeneity in the studies selected for this work. The researchers used forest plots, funnel plots and I2 to assess this heterogeneity. The estimated standard deviation was the interquartile range (IQR) / 1.35 for the studies that reported the mean and the IQR, while combining the reporting subgroups according to the Cochrane Handbook.
Study results
The authors identified 39 observational studies, including 33 published manuscripts, three conference abstracts, and three previous impressions. All studies performed CPET in more than 2,000 individuals, with nearly 1,000 suffering from LC. Although most of these studies performed CPET assessments three to six months after SARS-CoV-2 infection, one study investigated CPET after one year of infection. In particular, there was a cardiac rehabilitation study reporting baseline CPET.
The remaining 85% of the studies were case series from a single patient center attending LC clinics, and three studies included longitudinal CPET. About 41% of the included studies evaluated only hospitalized individuals and an average of 89% of the studies examined symptomatic cases. Because the number of studies included was small, the researchers did not perform publication bias tests.
The results of the meta-analysis confirmed that, compared with uninfected controls, individuals infected with SARS-CoV-2 had significantly lower maximum VO2 and high heterogeneity. Similarly, among individuals recovered with LC and COVID-19, the meta-analysis showed reduced exercise capacity among those with LC. Because no study evaluated CPETs prior to COVID-19, the authors were unable to compare individual changes. Few studies addressed confounding factors, such as age, gender, body mass index, pre-infection fitness, and comorbid heart and lung conditions. Only two studies, including the current study, showed an adjusted difference in maximum VO2 between those with and without LC.
Regarding the mechanisms for reducing exercise capacity in LC, the authors more often identified deconditioning, although identifying the direct effects was a challenge. Other reported patterns include dysfunctional respiration, changes in peripheral oxygen utilization, chronotropic incompetence, and increased systolic volume. The results clarified that direct heart or lung damage was not the main driver of exercise limitations.
Conclusions
In conclusion, the study showed that people hospitalized for severe COVID-19 and those with LC had reduced exercise capacity. However, due to the heterogeneity in the inclusion criteria, diverse interpretations and multiple underlying mechanisms instead of one; therefore, the study was unable to establish mechanisms of LC or etiology of reduced exercise capacity.
Therefore, the authors highlighted the conduct of longitudinal studies to investigate the trajectory of exercise capacity. They also recommended the use of CPET in intervention trials for possible LC therapies.
* Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice or health-related behavior, or treated as established information.