Low Cardiorespiratory Fitness Post-COVID-19: A Narrative Review

Abstract

Patients recovering from COVID-19 often report symptoms of exhaustion, fatigue and dyspnoea and present with exercise intolerance persisting for months post-infection. Numerous studies investigated these sequelae and their possible underlying mechanisms using cardiopulmonary exercise testing. We aimed to provide an in-depth discussion as well as an overview of the contribution of selected organ systems to exercise intolerance based on the Wasserman gears. The gears represent the pulmonary system, cardiovascular system, and periphery/musculature and mitochondria. Thirty-two studies that examined adult patients post-COVID-19 via cardiopulmonary exercise testing were included. In 22 of 26 studies reporting cardiorespiratory fitness (herein defined as peak oxygen uptake-VO_2peak), VO_2peak was < 90% of predicted value in patients. VO_2peak was notably below normal even in the long-term. Given the available evidence, the contribution of respiratory function to low VO_2peak seems to be only minor except for lung diffusion capacity. The prevalence of low lung diffusion capacity was high in the included studies. The cardiovascular system might contribute to low VO_2peak via subnormal cardiac output due to chronotropic incompetence and reduced stroke volume, especially in the first months post-infection. Chronotropic incompetence was similarly present in the moderate- and long-term follow-up. However, contrary findings exist. Peripheral factors such as muscle mass, strength and perfusion, mitochondrial function, or arteriovenous oxygen difference may also contribute to low VO_2peak. More data are required, however. The findings of this review do not support deconditioning as the primary mechanism of low VO_2peak post-COVID-19. Post-COVID-19 sequelae are multifaceted and require individual diagnosis and treatment.

Fig. 1

The figure illustrates leverage points through which COVID-19 could directly and/or indirectly induce low $\dot{V}$O_2peak and exercise intolerance in patients post-COVID-19. Parameters on the left side of the figure reflect the status quo of the gears (i.e. pulmonary system, cardiovascular system and periphery) and are indicative of organ limitations. The original concept of the gear system explaining determinants of $\dot{V}$O_2peak is available in Wasserman [9]. a-vO₂ diff arteriovenous oxygen difference. CO cardiac output, COVID-19 coronavirus disease 2019, CRF cardiorespiratory fitness, FEV1 forced expiratory volume in 1 s, FVC forced vital capacity, Hb haemoglobin, HR heart rate, SV stroke volume, $\dot{V}$O_2peak peak oxygen uptake

Fig. 2

Medians of $\dot{V}$O_2peak (A), DLCO (B) and V̇E/V̇CO₂ (C) weighted by sample size of respective studies or study visits in case a cohort was tested several times. Bubble area represents the sample size of studies. Bubble colour reflects COVID-19 severity of the majority of patients in the respective study (yellow = mild, dark red = critical). Grey bubbles: classification according to COVID-19 severity not possible. DLCO lung diffusion capacity using carbon monoxide, LT long term, MT medium term, ST short term, V̇E/V̇CO₂ ventilatory efficiency, $\dot{V}$O_2peak peak oxygen uptake