Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge

Abstract Severe symptoms in the absence of measurable body pathology are a frequent hallmark of post-COVID syndrome. From a Bayesian Brain perspective, such symptoms can be explained by incorrect internal models that the brain uses to interpret sensory signals. In this pre-registered study, we inves...

Full description

Saved in:
Bibliographic Details
Main Authors: Dina von Werder, Maria Aubele, Franziska Regnath, Elisabeth Tebbe, Dejan Mladenov, Victoria von Rheinbaben, Elisabeth Hahn, Daniel Schäfer, Katharina Biersack, Kristina Adorjan, Hans C. Stubbe, Katleen Bogaerts, Rudolf A. Jörres, Dennis Nowak, Omer Van den Bergh, Stefan Glasauer, Nadine Lehnen
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-11728-x
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849345205428289536
author Dina von Werder
Maria Aubele
Franziska Regnath
Elisabeth Tebbe
Dejan Mladenov
Victoria von Rheinbaben
Elisabeth Hahn
Daniel Schäfer
Katharina Biersack
Kristina Adorjan
Hans C. Stubbe
Katleen Bogaerts
Rudolf A. Jörres
Dennis Nowak
Omer Van den Bergh
Stefan Glasauer
Nadine Lehnen
author_facet Dina von Werder
Maria Aubele
Franziska Regnath
Elisabeth Tebbe
Dejan Mladenov
Victoria von Rheinbaben
Elisabeth Hahn
Daniel Schäfer
Katharina Biersack
Kristina Adorjan
Hans C. Stubbe
Katleen Bogaerts
Rudolf A. Jörres
Dennis Nowak
Omer Van den Bergh
Stefan Glasauer
Nadine Lehnen
author_sort Dina von Werder
collection DOAJ
description Abstract Severe symptoms in the absence of measurable body pathology are a frequent hallmark of post-COVID syndrome. From a Bayesian Brain perspective, such symptoms can be explained by incorrect internal models that the brain uses to interpret sensory signals. In this pre-registered study, we investigate whether induced breathlessness perception during a controlled CO2rebreathing challenge is reflected by altered respiratory measures (physiology and breathing patterns), and propose different computational mechanisms that could explain our findings in a Bayesian Brain framework. We analysed data from 40 patients with post-COVID syndrome and 40 healthy participants. Results from lung function, neurological and neurocognitive examination of all participants were within normal limits on the day of the experiment. Using a Bayesian repeated-measures ANOVA, we found that patients’ breathlessness was strongly increased (BF10,baseline =8.029, BF10,rebreathing =11636, BF10,recovery =43662) compared to controls. When excluding patients who hyperventilated (N = 8, 20%) during the experiment from the analysis, differences in breathlessness remained (BF10,baseline =1.283, BF10,rebreathing =126.812, BF10,recovery =751.282). For physiology and breathing patterns, all evidence pointed towards no difference between the two groups (0.307 > BF10 < 0.704). In summary, we found intact breathing patterns and physiology but increased symptom perception in patients with post-COVID syndrome.
format Article
id doaj-art-fecc93ac0db543f0b6cfaf480f67dd02
institution Kabale University
issn 2045-2322
language English
publishDate 2025-07-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-fecc93ac0db543f0b6cfaf480f67dd022025-08-20T03:42:31ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-11728-xIncreased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challengeDina von Werder0Maria Aubele1Franziska Regnath2Elisabeth Tebbe3Dejan Mladenov4Victoria von Rheinbaben5Elisabeth Hahn6Daniel Schäfer7Katharina Biersack8Kristina Adorjan9Hans C. Stubbe10Katleen Bogaerts11Rudolf A. Jörres12Dennis Nowak13Omer Van den Bergh14Stefan Glasauer15Nadine Lehnen16Institute of Medical Technology, Brandenburg University of Technology Cottbus- SenftenbergDepartment of Psychosomatic Medicine and Psychotherapy, TUM University Hospital, Technical University MunichDepartment of Psychosomatic Medicine and Psychotherapy, TUM University Hospital, Technical University MunichDepartment of Psychosomatic Medicine and Psychotherapy, TUM University Hospital, Technical University MunichDepartment of Psychosomatic Medicine and Psychotherapy, TUM University Hospital, Technical University MunichDepartment of Psychosomatic Medicine and Psychotherapy, TUM University Hospital, Technical University MunichDepartment of Psychosomatic Medicine and Psychotherapy, TUM University Hospital, Technical University MunichDepartment of Psychosomatic Medicine and Psychotherapy, TUM University Hospital, Technical University MunichDepartment of Psychosomatic Medicine and Psychotherapy, TUM University Hospital, Technical University MunichUniversity Hospital of Psychiatry and Psychotherapy, University of BernDepartment of Medicine II, LMU University Hospital, LMU MunichREVAL – Rehabilitation Research Center, Faculty of Rehabilitation Sciences, Hasselt UniversityInstitute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMUInstitute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMUREVAL – Rehabilitation Research Center, Faculty of Rehabilitation Sciences, Hasselt UniversityInstitute of Medical Technology, Brandenburg University of Technology Cottbus- SenftenbergGraduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität MünchenAbstract Severe symptoms in the absence of measurable body pathology are a frequent hallmark of post-COVID syndrome. From a Bayesian Brain perspective, such symptoms can be explained by incorrect internal models that the brain uses to interpret sensory signals. In this pre-registered study, we investigate whether induced breathlessness perception during a controlled CO2rebreathing challenge is reflected by altered respiratory measures (physiology and breathing patterns), and propose different computational mechanisms that could explain our findings in a Bayesian Brain framework. We analysed data from 40 patients with post-COVID syndrome and 40 healthy participants. Results from lung function, neurological and neurocognitive examination of all participants were within normal limits on the day of the experiment. Using a Bayesian repeated-measures ANOVA, we found that patients’ breathlessness was strongly increased (BF10,baseline =8.029, BF10,rebreathing =11636, BF10,recovery =43662) compared to controls. When excluding patients who hyperventilated (N = 8, 20%) during the experiment from the analysis, differences in breathlessness remained (BF10,baseline =1.283, BF10,rebreathing =126.812, BF10,recovery =751.282). For physiology and breathing patterns, all evidence pointed towards no difference between the two groups (0.307 > BF10 < 0.704). In summary, we found intact breathing patterns and physiology but increased symptom perception in patients with post-COVID syndrome.https://doi.org/10.1038/s41598-025-11728-x
spellingShingle Dina von Werder
Maria Aubele
Franziska Regnath
Elisabeth Tebbe
Dejan Mladenov
Victoria von Rheinbaben
Elisabeth Hahn
Daniel Schäfer
Katharina Biersack
Kristina Adorjan
Hans C. Stubbe
Katleen Bogaerts
Rudolf A. Jörres
Dennis Nowak
Omer Van den Bergh
Stefan Glasauer
Nadine Lehnen
Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge
Scientific Reports
title Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge
title_full Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge
title_fullStr Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge
title_full_unstemmed Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge
title_short Increased breathlessness in post-COVID syndrome despite normal breathing patterns in a rebreathing challenge
title_sort increased breathlessness in post covid syndrome despite normal breathing patterns in a rebreathing challenge
url https://doi.org/10.1038/s41598-025-11728-x
work_keys_str_mv AT dinavonwerder increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT mariaaubele increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT franziskaregnath increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT elisabethtebbe increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT dejanmladenov increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT victoriavonrheinbaben increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT elisabethhahn increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT danielschafer increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT katharinabiersack increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT kristinaadorjan increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT hanscstubbe increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT katleenbogaerts increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT rudolfajorres increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT dennisnowak increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT omervandenbergh increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT stefanglasauer increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge
AT nadinelehnen increasedbreathlessnessinpostcovidsyndromedespitenormalbreathingpatternsinarebreathingchallenge