Cardiopulmonary Testing In Long Covid Versus Non-CovidPatients With Undifferentiated Dyspnea On Exertion

Background: COVID-19 reveals new manifestations not only in the acute phase but also in the long term. The latter is what has been termed as ‘post acute sequelae of SARS-CoV-2 infection’ (PASC) — or “long COVID”— with dyspnea as one of its hallmarks. Cardiopulmonary stress testing (CPET) is increasingly being used to better evaluate such patients. Objective: To compare CPET findings of long COVID patients versus non-COVID patients with undifferentiated dyspnea on exertion seen at Mayo Clinic. Methods: A cohort study was carried out using Mayo Clinic’s exercise testing database. The study group included 77 PASC patients confirmed by a positive antigen or PCR test with no prior history of heart or lung disease. PASC patients were compared to 766 non-COVID patients with unspecified dyspnea without known diagnosis of cardiac or pulmonary disease. ANOVA according to the general linear model and Pearson’s Chi square were used for the bivariate analysis of the quantitative and categorical variables, respectively. Analyses were controlled for age, sex, and beta blocker use as appropriate. Both HR and SBP at rest and peak exercise were significantly different between groups, although the absolute differences were small. Results: Compared with the control group, the post-COVID patients were younger (mean age 47 SD ±14.9 years versus 50.5 SD ±10.1 years) and more likely to be female (70.1% (54 of 77) vs 57.6% (441 of 766)). Although there were many significant differences in the CPET results, the most outstanding were a lower FAC (73 SD ±19.4% vs 85.2 SD ±20.8%) and peak VO2 (22 SD ±6.4 ml/kg/min vs 25.8 SD ±7.37 ml/kg/min) in the study group (p<.0001). Also, CNS changes during CPET were reported at higher rates (19.5% (15 of 77) vs 11.4% (87 of 766)) while dyspnea at lower rates (55.8% (43 of 77) vs 65.7% (503 of 766)) in post-COVID patients (p=0.02). When adjusting for age and sex, weight was significantly higher in the study group (p=0.03) although the absolute difference was modest and BMI remained not significant. PFTs did not suggest any pulmonary abnormalities. Conclusions: We identified a high rate of severe exercise limitation among long COVID patients. Young women may be at higher risk for these complications. Pre-exercise PFTs and absence of objective respiratory limitation during CPET argue against a primary pulmonary cause of the observed limitations, though evaluation of cardiac, autonomic, and muscular impairment is pending. Further studies are warranted to untangle the physiologic abnormalities responsible for these observations.