Posted in a recent study medrxiv* Pre-print server, researchers demonstrate reduced exercise capacity due to persistent cardiopulmonary symptoms among coronavirus disease 2019 (COVID-19) patients hospitalized for acute infection and those with prolonged COVID (LC).
LC, a type of post-acute sequelae of COVID-19 (PASC), is quite common following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Studies have shown that 3–30% of individuals including non-hospitalized and COVID-19-vaccinated individuals suffer from LC which can persist for at least 12 months.
Cardiopulmonary exercise testing (CPET) assists in the differential diagnosis of a patient’s exercise limitations. It measures cardiopulmonary parameters and monitors cardiopulmonary symptoms while exercising on a treadmill. Oxygen consumption measurement allows determination of exercise capacity, and maximum oxygen consumption, or VO.2 (in ml/kg/min).
This data is clinically important and routinely used to diagnose dyspnea and prehistorically in congestive heart failure, lung diseases and pre-operation evaluation. More importantly, the CPET data help to evaluate reduced exercise capacity among adults with and without LC. However, the relationship between exercise intolerance and LC and the underlying pathophysiology is uncertain.
In the current study, researchers explored large-scale research studies that used CPET to evaluate exercise capacity in adults who contracted SARS-CoV-2 infection at least three months prior. Search includes publisher Medline (PubMed), Excerpt Medica (EMBASE), and Web of Science databases; The team used keywords such as cardiopulmonary exercise test, CPET, CPX, CPEX, exercise capacity, SARS-CoV-2 with VO.2Anaerobic threshold, optimized for databases.
The researchers collected cohort studies, case series, and baseline data from interventional studies. They ran this search first on December 20, 2021, then on May 24, 2022; However, they searched for pre-prints until June 9, 2022. The team used REDCap for independent data extraction in duplicate. Similarly, they used the study population, the quality of the CPET exercise protocol, the Cochrane Quality in Predictive Study Tool to assess peak VO.2 and sub-maximum test estimation, confounding, reporting, and statistical analysis.
In addition, he achieved peak VO . performed a random-effects meta-analysis to estimate the mean difference in2 LC and SARS-CoV-2 between people with and without infection. Patient and control selection introduced a high degree of heterogeneity among the studies examined 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 those studies that reported the median and IQR, while they combined those reporting subgroups according to the Cochrane Handbook.
The authors identified 39 observational studies, including 33 published manuscripts, three conference abstracts and three pre-prints. All studies performed CPET on over 2000 individuals, with approximately 1000 suffering from LC. While most of these studies evaluated CPET between three and six months after SARS-CoV-2 infection, one study examined CPET one year after infection. Notably, there was a cardiac rehabilitation study reporting baseline CPET.
The remaining 85% of the studies were single-center case series of patients attending LC clinics, and three studies included longitudinal CPET. Approximately 41% of the included studies only evaluated hospitalized individuals, and an average of 89% of the studies examined symptomatic cases. Because the number of included studies was small, the researchers did not test for publication bias.
The results of the meta-analysis confirmed that compared with uninfected controls, SARS-CoV-2 infected individuals had significantly lower VO levels.2 and high heterogeneity. Similarly, among individuals with LC versus COVID-19 recovered, a meta-analysis showed lower exercise capacity in those with LC. Since none of the studies evaluated pre-COVID-19 CPET, the authors could not compare individual changes. Some studies looked at confounding factors, such as age, gender, body mass index, fitness before infection, and comorbid cardiac and pulmonary conditions. Only two studies, including the present study, reported peak VO. The adjusted difference is displayed in2 Between those with and without LC.
With regard to the mechanism of reduced exercise capacity in the LC, the authors most commonly identified deconditioning, although identifying direct effects was challenging. Other reported patterns include passive breathing, changes in peripheral oxygen use, chronotropic dysfunction, and reduced stroke volume increase. The findings clarified that direct heart or lung damage was not the primary driver of exercise limitations.
To conclude, the study demonstrated that individuals hospitalized for severe COVID-19 and those with LC had reduced exercise capacity. However, due to diversity in inclusion criteria, diverse interpretations, and multiple underlying mechanisms rather than one; Thus, the study could not establish the mechanism of etiology of LC or reduced exercise capacity.
Therefore, the authors insisted on conducting longitudinal studies to investigate the trajectory of exercise capacity. They also recommended using CPET in conventional trials for potential LC therapeutics.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, should guide clinical practice/health-related behavior, or be regarded as established information.