Exercise Intolerance in Post-COVID Patients

NCT ID: NCT05445830

Last Updated: 2025-09-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-01

Study Completion Date

2025-12-31

Brief Summary

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The post-COVID syndrome poses an unprecedented challenge to modern society, affecting millions of people worldwide. Persistent fatigue and exercise intolerance are among the most common complaints of these subjects. The mechanisms of exercise intolerance in post-COVID subjects are remained yet unknown, which make the rehabilitation efforts complex and challenging. The overall goals of this project are to: 1) improve physiological understanding of symptoms in this clinical condition, 2) elucidate plausible mechanisms to explain exercise intolerance/symptom exacerbation, and finally 3) provide knowledge that can be directly applied in the clinical setting to improve diagnosis, care, and individualized rehabilitation of subjects with post-COVID syndrome. Post-COVID subjects and age/sex matched healthy controls will undertake a comprehensive set of physiological and functional assessments, followed by 3 experimental visits (in a randomized order), where acute exercise responses will be assessed in either continuous moderate intensity aerobic exercise, high intensity interval exercise, or strength training. The same set of physiological assessments will also be performed after 1 year in both post-COVID subjects and healthy-matched controls to better understand the time course of the syndrome. It is hypothesized that the mechanism responsible for exercise intolerance is linked to specific symptoms and will vary across subjects. However, it is expected that most post-COVID subjects will respond well to at least one type of exercise.

Detailed Description

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Conditions

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Post-COVID Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators
Upon collection, data will be pseudonymized (both group and intervention) to facilitate unbiased analysis.

Study Groups

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Post-covid patients

Group Type EXPERIMENTAL

High-Intensity-Interval-Exercise

Intervention Type PROCEDURE

Subjects will perform high-intensity-interval exercise, where the acute exercise responses will be closely monitored, including measurements of O2 saturation, heart rate, blood pressure, borg scale and blood lactate. In addition, symptoms via multiple validated questionnaries and blood samples will be collected before, immediately after each exercise session to describe leukocyte and cytokine release as well as systemic metabolism. After a 48-hour rest period subjects will return to the laboratory for symptom assessment, submaximal exercise response (CPET), and blood sampling.

Moderate-Intensity-Continuous-Exercise

Intervention Type PROCEDURE

Subjects will perform moderate intensity continuous exercise, where the acute exercise responses will be closely monitored, including measurements of O2 saturation, heart rate, blood pressure, borg scale and blood lactate. In addition, symptoms via multiple validated questionnaries and blood samples will be collected before, immediately after each exercise session to describe leukocyte and cytokine release as well as systemic metabolism. After a 48-hour rest period subjects will return to the laboratory for symptom assessment, submaximal exercise response (CPET), and blood sampling.

Strength training

Intervention Type PROCEDURE

Subjects will perform a series of a whole-body resistance exercises, where the acute exercise responses will be closely monitored, including measurements of O2 saturation, heart rate, blood pressure, borg scale and blood lactate. In addition, symptoms via multiple validated questionnaries and blood samples will be collected before, immediately after each exercise session to describe leukocyte and cytokine release as well as systemic metabolism. After a 48-hour rest period subjects will return to the laboratory for symptom assessment, submaximal exercise response (CPET), and blood sampling.

Baseline assessment

Intervention Type PROCEDURE

Subjects will perform a series of baseline assessment including neurophysiological function, circulatory and vascular function, blood volume assessment, respiratory/ventilatory function, maximal oxygen uptake, strength, physical function and fitness, blood status and muscle biopsy.

1 year follow-up

Intervention Type PROCEDURE

Subjects will perform the same series of baseline assessment in 1-year time, including neurophysiological function, circulatory and vascular function, blood volume assessment, respiratory/ventilatory function, maximal oxygen uptake, strength, physical function and fitness, blood status and muscle biopsy.

Control

Group Type EXPERIMENTAL

High-Intensity-Interval-Exercise

Intervention Type PROCEDURE

Subjects will perform high-intensity-interval exercise, where the acute exercise responses will be closely monitored, including measurements of O2 saturation, heart rate, blood pressure, borg scale and blood lactate. In addition, symptoms via multiple validated questionnaries and blood samples will be collected before, immediately after each exercise session to describe leukocyte and cytokine release as well as systemic metabolism. After a 48-hour rest period subjects will return to the laboratory for symptom assessment, submaximal exercise response (CPET), and blood sampling.

Moderate-Intensity-Continuous-Exercise

Intervention Type PROCEDURE

Subjects will perform moderate intensity continuous exercise, where the acute exercise responses will be closely monitored, including measurements of O2 saturation, heart rate, blood pressure, borg scale and blood lactate. In addition, symptoms via multiple validated questionnaries and blood samples will be collected before, immediately after each exercise session to describe leukocyte and cytokine release as well as systemic metabolism. After a 48-hour rest period subjects will return to the laboratory for symptom assessment, submaximal exercise response (CPET), and blood sampling.

Strength training

Intervention Type PROCEDURE

Subjects will perform a series of a whole-body resistance exercises, where the acute exercise responses will be closely monitored, including measurements of O2 saturation, heart rate, blood pressure, borg scale and blood lactate. In addition, symptoms via multiple validated questionnaries and blood samples will be collected before, immediately after each exercise session to describe leukocyte and cytokine release as well as systemic metabolism. After a 48-hour rest period subjects will return to the laboratory for symptom assessment, submaximal exercise response (CPET), and blood sampling.

Baseline assessment

Intervention Type PROCEDURE

Subjects will perform a series of baseline assessment including neurophysiological function, circulatory and vascular function, blood volume assessment, respiratory/ventilatory function, maximal oxygen uptake, strength, physical function and fitness, blood status and muscle biopsy.

1 year follow-up

Intervention Type PROCEDURE

Subjects will perform the same series of baseline assessment in 1-year time, including neurophysiological function, circulatory and vascular function, blood volume assessment, respiratory/ventilatory function, maximal oxygen uptake, strength, physical function and fitness, blood status and muscle biopsy.

Interventions

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High-Intensity-Interval-Exercise

Subjects will perform high-intensity-interval exercise, where the acute exercise responses will be closely monitored, including measurements of O2 saturation, heart rate, blood pressure, borg scale and blood lactate. In addition, symptoms via multiple validated questionnaries and blood samples will be collected before, immediately after each exercise session to describe leukocyte and cytokine release as well as systemic metabolism. After a 48-hour rest period subjects will return to the laboratory for symptom assessment, submaximal exercise response (CPET), and blood sampling.

Intervention Type PROCEDURE

Moderate-Intensity-Continuous-Exercise

Subjects will perform moderate intensity continuous exercise, where the acute exercise responses will be closely monitored, including measurements of O2 saturation, heart rate, blood pressure, borg scale and blood lactate. In addition, symptoms via multiple validated questionnaries and blood samples will be collected before, immediately after each exercise session to describe leukocyte and cytokine release as well as systemic metabolism. After a 48-hour rest period subjects will return to the laboratory for symptom assessment, submaximal exercise response (CPET), and blood sampling.

Intervention Type PROCEDURE

Strength training

Subjects will perform a series of a whole-body resistance exercises, where the acute exercise responses will be closely monitored, including measurements of O2 saturation, heart rate, blood pressure, borg scale and blood lactate. In addition, symptoms via multiple validated questionnaries and blood samples will be collected before, immediately after each exercise session to describe leukocyte and cytokine release as well as systemic metabolism. After a 48-hour rest period subjects will return to the laboratory for symptom assessment, submaximal exercise response (CPET), and blood sampling.

Intervention Type PROCEDURE

Baseline assessment

Subjects will perform a series of baseline assessment including neurophysiological function, circulatory and vascular function, blood volume assessment, respiratory/ventilatory function, maximal oxygen uptake, strength, physical function and fitness, blood status and muscle biopsy.

Intervention Type PROCEDURE

1 year follow-up

Subjects will perform the same series of baseline assessment in 1-year time, including neurophysiological function, circulatory and vascular function, blood volume assessment, respiratory/ventilatory function, maximal oxygen uptake, strength, physical function and fitness, blood status and muscle biopsy.

Intervention Type PROCEDURE

Other Intervention Names

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HIIE MICE Resistance training

Eligibility Criteria

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Inclusion Criteria

* Verified test of covid-19 infection (PCR, or antigen or antibody before vaccination) (mandatory only for post-COVID group)
* Symptoms persisting for at least 3 months (validaded with DSQ-PEM questionnarie) (only for post-COVID group)

Exclusion Criteria

* Subject's complaints may have been present before March 2020
* Previous history cardiovascular, respiratory disease or other autoimmune disease
* History of general anxiety syndrome or somatic symptom disorder
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Karolinska University Hospital

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role lead

Responsible Party

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Tommy Lundberg

Lecturer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas Gustafsson, Prof

Role: STUDY_CHAIR

Karolinska Institutet and Karolinska University Hospital

Helene Rundqvist, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Tommy Lundberg, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Kaveh Pourhamidi, PhD

Role: STUDY_CHAIR

Karolinska University Hospital

Andrea Tryfonos, PhD

Role: STUDY_DIRECTOR

Karolinska Institutet

Locations

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Karolinska University Hospital Huddinge

Stockholm, Huddinge, Sweden

Site Status

Countries

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Sweden

References

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Tryfonos A, Jornaker G, Rundqvist H, Pourhamidi K, Melin M, Wallin H, Larsen FJ, Pantelios S, Mutvei AP, Tillander V, Tietge UJF, Diaz SP, Crafoord D, Lovric A, Fernandez-Gonzalo R, Rullman E, Stal P, Gustafsson T, Rundqvist H, Lundberg TR. Muscle Abnormalities in Nonhospitalised Patients With Post-COVID-19 Condition. J Cachexia Sarcopenia Muscle. 2025 Oct;16(5):e70085. doi: 10.1002/jcsm.70085.

Reference Type DERIVED
PMID: 41030235 (View on PubMed)

Tryfonos A, Pourhamidi K, Jornaker G, Engvall M, Eriksson L, Elhallos S, Asplund N, Mandic M, Sundblad P, Sepic A, Rullman E, Hyllienmark L, Rundqvist H, Lundberg TR, Gustafsson T. Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition: A Randomized Crossover Clinical Trial. JAMA Netw Open. 2024 Apr 1;7(4):e244386. doi: 10.1001/jamanetworkopen.2024.4386.

Reference Type DERIVED
PMID: 38573638 (View on PubMed)

Other Identifiers

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2021-05758-01

Identifier Type: -

Identifier Source: org_study_id

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