Exercise Intolerance in Post-COVID Patients

NCT05445830 | Active Not Recruiting

• 1 other identifier: 2021-05758-01
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Post-COVID Syndrome

Keywords

Exercise intolerance; Acute exercise; Skeletal muscle; Cardiorespiratory fitness; Post-COVID syndrome

Outcome Measures

Primary Outcomes (1)

• Post-exertional malaise (PEM) symptoms of post-COVID subjects and age/sex matched controls in response to different exercise trials.

  Visual analog scale (VAS) 0-10 for 10 symptoms (fatigue, muscle pain, joint pain, memory, concentration, fever, sore throat, lymph nodes, headache, chills) will be used to assess symptoms exaggeration in response to 3 different exercise trials (high intensity interval training, moderate intensity continuous exercise and strength exercise) between the post-COVID subjects and age/sex matched controls. 0=no pain/symptom to 10=maximal pain/symptom 2 groups x 3 exercise sessions x 3 timepoints per exercise (pre, post and 48h post)

  Three exercises trials & 48 hours follow-ups of each trial

Secondary Outcomes (19)

• Absolute immune cell count in blood samples of post-COVID subjects and age/sex matched controls in response to different exercise trials.

  Three exercises trials & 48 hours follow-ups of each exercise trial

• Exploratory metabolomic and cytokine profiling using blood samples of post-COVID subjects and age/sex matched controls in response to different exercise trials.

  Three exercises trials & 48 hours follow-ups of each exercise trial

• Cardiac function in the post-COVID subjects and age/sex matched controls

  Baseline & 1y follow-up

• Respiratory function in the post-COVID subjects and age/sex matched controls

  Baseline & 1y follow-up

• Arterial stiffness in the post-COVID subjects and age/sex matched controls

  Baseline & 1y follow-up

Study Arms (2)

Post-covid patients

EXPERIMENTAL

Procedure: High-Intensity-Interval-Exercise; Procedure: Moderate-Intensity-Continuous-Exercise; Procedure: Strength training; Procedure: Baseline assessment; Procedure: 1 year follow-up

Control

EXPERIMENTAL

Procedure: High-Intensity-Interval-Exercise; Procedure: Moderate-Intensity-Continuous-Exercise; Procedure: Strength training; Procedure: Baseline assessment; Procedure: 1 year follow-up

Interventions

High-Intensity-Interval-Exercise 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.

Also known as: HIIE

Control; Post-covid patients

Moderate-Intensity-Continuous-Exercise 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.

Also known as: MICE

Control; Post-covid patients

Strength training 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.

Also known as: Resistance training

Control; Post-covid patients

Baseline assessment 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.

Control; Post-covid patients

1 year follow-up 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; Post-covid patients

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator

Study Sites (1)

Karolinska University Hospital Huddinge

Stockholm, Huddinge, 141 57, Sweden

Location

Related Publications (2)

• 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.

  PMID: 41030235 DERIVED

• 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.

  PMID: 38573638 DERIVED

MeSH Terms

Interventions

High-Intensity Interval Training; Resistance Training

Intervention Hierarchy (Ancestors)

Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities

Study Officials

• Thomas Gustafsson, Prof

  Karolinska Institutet and Karolinska University Hospital

  STUDY CHAIR

• Helene Rundqvist, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Tommy Lundberg, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Kaveh Pourhamidi, PhD

  Karolinska University Hospital

  STUDY CHAIR

• Andrea Tryfonos, PhD

  Karolinska Institutet

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Upon collection, data will be pseudonymized (both group and intervention) to facilitate unbiased analysis.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer

Study Record Dates

• First Submitted: July 2, 2022
• First Posted: July 6, 2022
• Study Start: September 1, 2022
• Primary Completion: September 15, 2023
• Study Completion: December 31, 2025
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Documents will be made available when the summary data are published.

Locations

SE (1)