Dysfunctional respiratory processing in patients with post-COVID? – An experimental-computational approach investigating the interaction between breathing behaviour and symptom perception

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In the proposed study, we aim to develop objective, pathophysiological markers of breathlessness in post-COVID. We will combine experimental methods with computational modeling to investigate breathlessness and respiratory behavior, their interaction, and hypotheses about respiratory signal processing in post-COVID patients. We use an established rebreathing paradigm that allows determination of the interaction between breathlessness and physiological parameters. Previous studies have shown that in this rebreathing experiment, patients with organically unexplained breathlessness exhibit characteristic, measurable deviations in breathlessness compared to healthy individuals. These deviations occur only in specific contexts and indicate altered processing of respiratory information in the central nervous system (CNS). In the present study, we will use this paradigm to investigate whether such characteristic changes (in perceived breathlessness and/or in physiological respiratory parameters and patterns) occur in patients with post-COVID breathlessness, and whether they are altered by different contexts. The combination of an experimental approach and theoretical modeling of breathlessness at the level of individual patients allows us to test detailed hypotheses about the processing of respiratory signals in the development of breathlessness. For this purpose, we have developed a preliminary mathematical model of breathlessness processing. It already shows good results in predicting mean data from previous studies and initial pilot data from individual subjects using the rebreathing paradigm. Objective, pathophysiological markers are an important first step towards reducing stigma and individualized planning of diagnosis and therapy in patients with post-COVID.