Fat Oxidation Capacity in Patients With Post Covid-19 Syndrome

Analysis of Fat Oxidation Capacity During Cardiopulmonary Exercise Testing Indicates Long-lasting Metabolic Disturbance in Patients With Post-COVID-19 Syndrome

Post-COVID-19 Syndrome (PCS) is characterized by symptoms, including fatigue, reduced physical performance, dyspnea, cognitive impairment, and psychological distress. The mechanisms underlying the onset and severity of PCS point to mitochondrial dysfunction as significant contributor. This study examined fat oxidation as a function of mitochondrial capacity during exercise.

Study Overview

• Status: Completed
• Conditions: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome
• Intervention / Treatment: Behavioral: Exercise-based rehabilitation

Detailed Description

Post-COVID-19 Syndrome (PCS), also known as post-acute sequelae of COVID-19, manifests following an acute infection with the SARS-CoV-2 virus (COVID-19 infection). PCS is characterized by the persistence of symptoms beyond 12 weeks from the onset of infection and/or the emergence of new symptoms within this time. Although recent guidelines offer specific criteria to diagnose PCS, ambiguity persists due to the complex nature of its symptomatology and the lack of definitive diagnostic tools. PCS is a multisystemic disorder characterized by symptoms such as (chronic) fatigue, diminished physical performance, muscular weakness and pain, dyspnea, cognitive impairments and alterations of the autonomous nervous system, as well as mental and psychological distress. The severity of symptoms varies widely among patients, from mild impairment to significant restrictions in daily activities, potentially leading to partial or complete incapacity to work. Of note, the severity of the acute infection does not predict the onset or severity of PCS. Even though many patients experience gradual recovery without specific treatment, there is a substantial need for effective medical rehabilitation, especially for those with persistent PCS. To this respect, exercise-based programs have been shown to induce significantly exercise capacity as well as higher quality of life, reduced fatigue, and less depression. Despite ongoing investigations, the mechanisms contributing to the onset and severity of PCS remain largely unknown. Factors may include endothelial dysfunction and detrimental effects on the microvasculature, as well as a "cytokine storm" associated with excessive oxidative stress and subsequent mitochondrial dysfunction which has emerged as a significant potential contributor.

Notably, detrimental effects on mitochondrial function have been described as a result of severe acute infections triggering an excessive immune response, systemic inflammation and oxidative stress. Recent studies suggested that impaired mitochondrial function in PCS may be associated with impaired fatty acid oxidation (FatOx) which can be identified using cardiopulmonary exercise testing (CPET). Currently, the number of PCS patients characterized for changes in FatOx using CPET is low and associations with signs and symptoms of PCS such as fatigue have not been reported in detail. Moreover, reports on the potential of exercise-based rehabilitation to restore FatOx capacity in PCS are not available. Thus, the current study aimed to investigate if analysis of breath-by-breath spirometric data followed by an estimation of individual FatOx capacity can be used for the stratification of PCS patients. The investigators hypothesized that a lower FatOx potential would be associated with PCS-specific signs and symptoms such as mental and physical fatigue. In addition, the investigators sought to analyze if exercise-based rehabilitation would be effective in restoring PCS patients' FatOx capacity as a sign of improved mitochondrial function.

• Study Type: Observational
• Enrollment (Actual): 187

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Ennepetal, NRW, Germany, 58256
      • Clinic Königsfeld

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Post-COVID-19 syndrome who are referred to Clinic Königsfeld for inpatient medical rehabilitation and who are willing to participate in the study and give their written informed consent. Inclusion criteria were a history of (at least one) COVID-19 infection (positive PCR test at the time of infection), and ongoing or newly expressed performance deficits lasting for at least 3 months prior to recruitment.

Description

Inclusion Criteria:

• a history of (at least one) Covid-19 infection
• ongoing or newly expressed performance deficits lasting for at least 3 months prior to recruitment
• referral to inpatient rehabilitation
• signed informed consent

Exclusion Criteria:

• unstable condition
• incapable of understanding study information

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Post-Covid-19 Syndrome Patients	Behavioral: Exercise-based rehabilitation; Patients performed regular physical exercise during inpatient rehabilitation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fat Oxidation Rate	Fat oxidation will be assessed by breath-by-breath spiroergometry	Baseline and week 4 (i. e. before discharge)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Carbohydrate Oxidation Rate	Carbohydrate oxidation rate will be assessed by breath-by-breath spirometry	Baseline and week 4 (i. e. before discharge)
Change in Fatigue	Fatigue will be assessed using the "The Multidimensional Fatigue Inventory (MFI20)"	Baseline and week 4 (i. e. before discharge)

Collaborators and Investigators

• Sponsor: University of Witten/Herdecke
• Collaborators: Institut für Rehabilitationsforschung Norderney

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): May 21, 2024

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: June 19, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 21, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Fatigue; Mitochondrial Dysfunction; Exercise-based Rehabilitation; Long-COVID-19
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Disease; Chronic Disease; Post-Infectious Disorders; COVID-19; Syndrome; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: PCS_Fettoxidation

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No