English: "(a) Systemic oxygen delivery (DO2) between Post Acute Sequelae of SARS-CoV-2 infection (PASC) patients with mild (EO2peak-mild) and severely (EO2peak-severe) reduced peak systemic oxygen extraction (EO2) depicted in median and interquartile range. (b) Volcano plot depicting individual proteins expressed in EO2peak-mild and EO2peak-severe PASC groups. (c) Horizontal bar graph depicting enriched proteomic pathway analysis of EO2peak-severe PASC group (blue highlight indicates statistical significance, that is, p < 0.05. gray bars represent p > 0.05). (d) Horizontal bar graph depicting enriched proteomic pathway analysis of EO2peak-mild PASC group (red highlight indicates statistical significance, that is, p < 0.05. Gray bars represent p > 0.05). (e) Box plots of individual protein expression between PASC patients with EO2peak-mild and EO2peak-severe impaired peak systemic EO2 categorized according to their respective categorical functions of inflammation, metabolic reprogramming, endotheliopathy, or fibrosis (* represents p < 0.05 and ** represents p < 0.01). Horizontal bar graphs depicting KEGG and Gene Ontology proteomic analysis of EO2peak-mild and EO2peak-severe PASC groups (blue and red highlight indicates statistical significance, that is, p < 0.05. Gray bars represent p > 0.05). KEGG, Kyoto encyclopedia of genes and genomes."

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From abstract:

"We studied 21 consecutive iCPET in PASC patients with unexplained exertional intolerance. PASC patients were dichotomized into mildly reduced (EO2peak-mild) and severely reduced (EO2peak-severe) EO2 groups according to the median peak EO2 value. Proteomic profiling was performed on mixed venous blood plasma obtained at peak exercise during iCPET. PASC patients as a group exhibited depressed peak exercise aerobic capacity (peak VO2; 85 ± 18 vs. 131 ± 45% predicted; p = 0.0002) with normal systemic oxygen delivery, DO2 (37 ± 9 vs. 42 ± 15 mL/kg/min; p = 0.43) and reduced EO2 (0.4 ± 0.1 vs. 0.8 ± 0.1; p < 0.0001). PASC patients with EO2peak-mild exhibited greater DO2 compared to those with EO2peak-severe [42.9 (34.2–41.2) vs. 32.1 (26.8–38.0) mL/kg/min; p = 0.01]. The proteins with increased expression in the EO2peak-severe group were involved in inflammatory and fibrotic processes. In the EO2peak-mild group, proteins associated with oxidative phosphorylation and glycogen metabolism were elevated. In PASC patients with impaired EO2, there exist a spectrum of PASC phenotype related to differential aberrant protein expression and cardio-pulmonary physiologic response. PASC patients with EO2peak-severe exhibit a maladaptive physiologic and proteomic signature consistent with persistent inflammatory state and endothelial dysfunction, while in the EO2peak-mild group, there is enhanced expression of proteins involved in oxidative phosphorylation-mediated ATP synthesis along with an enhanced cardiopulmonary physiological response."

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From press release:

"Multiomic proteomic analysis of blood collected from these patients identified increased circulating levels of proteins implicated in the inflammatory and fibrotic processes among the PASC patients with severely-reduced oxygen extraction capacity, as well as increased levels of proteins associated with endothelial dysfunction, or the inner layer of blood vessels critical for normal function of the lungs in extracting oxygen."