Cardiopulmonary exercise testing as a vital sign in patients recovering from COVID-19

Countries around the world continue to address the largescale health and wellbeing impacts and the broader societal burden associated with the coronavirus disease 2019 (COVID2019). From an individual to global level, we continue to increase our understanding of the current and legacy impacts affecting population health. Pathophysiologic sequelae, both acute and chronic, are numerous in the individuals who have been infected [1,2]. Evidence also demonstrates that cardiorespiratory fitness (CRF) can be compromised following COVID19 infection[2]. The evidence that COVID-19 has upon CRF is not surprising given the potential impact the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has on the cardiac, pulmonary, and skeletal muscular systems, the three systems that have a primary influence on the CRF response [1,3,4]. The impact of COVID-19 on CRF is particularly important given the fact that this clinical measure is now considered a vital sign [5], a designation earned by an evidence base spanning several decades, which clearly demonstrates its robust: 1) prognostic and diagnostic value; 2) ability to gauge therapeutic efficacy; and 3) correlation with functional capacity and quality of life [6]. Of the various approaches to assessing CRF, cardiopulmonary exercise testing (CPX) remains the gold-standard, providing for the most noninvasive, comprehensive, and accurate assessment of CRF. In the context of COVID-19, CPX provides an ideal approach to assess intersection between pathophysiologic and clinical manifestations, allowing for refined account of the impact the viral infection has both cross-sectionally and longitudinally, most importantly during a bout of physical exertion in a controlled environment. Put simply, without CPX, the pathophysiologic impacts of COVID-19 that only manifest during physical exertion, or manifest more profoundly during physical exertion, would be missed entirely, preventing a holistic understanding of the clinical presentation. Aerobic capacity, quantified by peak oxygen consumption (VO2), and ventilatory efficiency, most commonly quantified by the minute ventilation/carbon dioxide production (VE/VCO2) slope, are two of the most-established measures obtained through CPX and several studies to date report the impact of COVID-19 on both [7]. Pleguezuelos et al. [8] performed CPX on healthy controls, patients diagnosed with ischemic heart disease (IHD), patients diagnosed with chronic obstructive pulmonary disease (COPD) and patients hospitalized for COVID-19; CPX was performed two months post-hospital discharge in the COVID-19 group. Compared to healthy controls [32.31(28.32–36.31) mlO2·kg ·min], peak VO2 was significantly reduced (p < 0.001) in all groups [COVID-19 group: 17.30 (14.82–19.78) mlO2·kg ·min, COPD group: 14.35 (12.97–15.73) mlO2·kg ·min, and IHD group: 18.82 (15.64– 22) mlO2·kg ·min]. Skjorten et al. [9] found 31% of the cohort has a percent-predicted peak VO2 less than 80% in patients that were hospitalized with COVID-19 and undertook a CPX three months post-discharge. Compared to subjects reporting no dyspnea during activities of daily living (n = 67, 62%), those reporting dyspnea (n = 59, 38%) had a significantly lower peak VO2 (31.9 ± 9.3 vs. 23.6 ± 7.9 mlO2·kg ·min, p < 0.001) and significantly higher VE/VCO2 slope (26.6 ± 4.4 vs. 28.9 ± 4.5, p < 0.01). Raman et al. [2] compared 58 patients hospitalized for COVID-19 to a healthy control group. Two to three months following hospital discharge due to COVID-19, 64% of the patients continued to report dyspnea and 55% continued to report fatigue. Compared to healthy controls, percent-predicted peak VO2 was significantly lower (80.5 ± 23.1% vs. 112.7 ± 27.0%, p < 0.0001), and the VE/VCO2 slope was significantly higher [33.4 (29.2–40.3) vs. 28.2 (26.7–30.0), p < 0.0001] in those hospitalized with COVID-19. Aparisi et al. [10] reported similar findings in a cohort previously hospitalized for COVID-19 and undergoing CPX at three-month follow-up; peak VO2 was significantly lower [17.8 (15.8–21.2) vs. 22.8 (18.8–27.7) mlO2·kg ·min, p < 0.001], and the VE/VCO2 slope was significantly higher [32.0 (28.1–37.4) vs. 29.4 (26.9–31.4), p < 0.05] in the 41 subjects (58.6%) who reported persistent dyspnea following discharge compared to the 29 subjects (41.4%) who were asymptomatic. These findings indicate that CPs can be safely performed in these patients represent an emerging phenotype in a significant percentage of patients hospitalized due to COVID-19 several months following discharge resulting in diminished aerobic capacity and ventilatory inefficiency with the primary subjective symptom indicative of these responses being persistent exertional dyspnea. As previously noted, CRF is now considered a vital sign, a designation particularly due to its robust prognostic significance [5]. Peak VO2 is a proven and established prognostic