Exercise Ventilatory Inefficiency in Post-COVID-19 Syndrome: Insights from a Prospective Evaluation

Abstract

Introduction: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. This study sought to identify clinical sequelae and their potential mechanism.

Methods: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up. An outpatient group was also evaluated. They underwent serial testing with a cardiopulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis, and quality of life questionaries.

Results: Patients with dyspnea (n = 41, 58.6%), compared with asymptomatic patients (n = 29, 41.4%), had a higher proportion of females (73.2 vs. 51.7%; p = 0.065) with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in the transthoracic echocardiogram and pulmonary function test. Patients who complained of persistent dyspnea had a significant decline in predicted peak VO₂ consumption (77.8 (64-92.5) vs. 99 (88-105); p < 0.00; p < 0.001), total distance in the six-minute walking test (535 (467-600) vs. 611 (550-650) meters; p = 0.001), and quality of life (KCCQ-23 60.1 ± 18.6 vs. 82.8 ± 11.3; p < 0.001). Additionally, abnormalities in CPET were suggestive of an impaired ventilatory efficiency (VE/VC_O2 slope 32 (28.1-37.4) vs. 29.4 (26.9-31.4); p = 0.022) and high PET_CO2 (34.5 (32-39) vs. 38 (36-40); p = 0.025).

Interpretation: In this study, >50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest a potential ventilation/perfusion mismatch or hyperventilation syndrome.

Keywords: cardiopulmonary exercise testing; dyspnea; post-COVID-19 syndrome; pulmonary function test; six-minute walking test; ventilatory inefficiency.

Figure 1

Quality of life assessment with Kansas City Cardiomyopathy Questionnaire (KCMQ). * (p < 0.01) and ** (p < 0.001) indicate significant differences.

Figure 2

Temporal dynamic changes of inflammatory markers and lymphocytes from hospital admission to follow-up in the hospitalized cohort. * Excludes outside values; ¥ (p < 0.05); † (p < 0.01); ‡ (p < 0.001).

Figure 3

Predictors of dyspnea among hospitalized and ambulatory patients.