Preload insufficiency as common denominator of exertional dyspnoea in distinct post-COVID phenotypes

IntroductionThe underlying causes of exertional dyspnoea and exercise limitation in post-COVID syndrome remain uncertain. We performed deep-phenotyping of post-COVID patients to evaluate limitations of ventilation, gas exchange and cardiopulmonary circulation in a multicentre, cross-sectional study. MethodsThe dyspnoea index and aerobic exercise performance (peakVO2) were determined by questionnaires and cardiopulmonary exercise testing, respectively, in a cohort of 86 post-COVID patients and 12 controls. Lung function, gas exchange and ventilation-perfusion mismatch were evaluated. Cardiac parameters were measured by echocardiography and, in a subgroup, systemic vascular characteristics by pulse wave analysis. ResultsPost-COVID patients showed low ventilation at peak exercise [VE(peak)], ventilatory inefficiency, low right heart dimensions and low basal oxygen uptake. In a multivariate regression analysis, ventilatory parameters - high breathing frequency at peak exercise ({beta}=0.15, p=0.004) and low forced expiratory volume in 1 s ({beta}=-0.33, p=0.007) - and right atrial end-systolic area index (RA ESAi; {beta}=-0.34, p<0.001) were independent predictors of dyspnoea, while low VE(peak) ({beta}=0.46, p<0.001) and low aerobic capacity ({beta}=0.51, p<0.001) independently predicted low peakVO2. Low RA ESAi was associated with a low diffusion coefficient (r=0.36), low end-tidal pCO2 (r=0.39) and high heart rate (r=-0.31). Subgroup analysis of patients showed specific associations between dyspnoea and diastolic and bronchial function, low blood pressure, hyperventilation or oxygen uptake. ConclusionPreload insufficiency associated with gas exchange disturbances contributes to the sensation of dyspnoea in post-COVID patients, as well as ventilatory limitations, while peakVO2 was predominantly associated with aerobic capacity. Three phenotypes were defined, indicating the need for tailored interventions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=155 SRC="FIGDIR/small/25328135v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@1f0733aorg.highwire.dtl.DTLVardef@11d1504org.highwire.dtl.DTLVardef@4ee543org.highwire.dtl.DTLVardef@1adc735_HPS_FORMAT_FIGEXP M_FIG C_FIG