Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue (COVID-Rehab)

The objective of this project is to assess the effects of a 2-month cardiopulmonary rehabilitation program on cardiorespiratory fitness in long COVID19 patients. Quality of life, functional capacity, functional respiratory capacity, inflammatory profile, coagulation markers, cognitive functions and brain O2 saturation will also be assessed before and after the exercise rehabilitation program.

Some symptoms such as breathlessness and fatigue appear to persist for several months after COVID-19 infection in about 50% of cases. Stress, anxiety, neurological and cognitive disorders have also been reported in the long-term side effects associated with the disease. Cardiopulmonary rehabilitation programs are recognized as an essential component of the management of people with chronic respiratory disease. These programs are based on exercise training with aerobic exercises, muscle strengthening, breathing exercises. Beyond the benefit on morbi-mortality, a marked improvement in symptoms, fitness and quality of life is observed in chronic respiratory diseases. Several hospital departments, research teams and scientific organizations as the WHO recommend the use of rehabilitation programs for COVID-19 patients. The main objective is to assess the effects of a 2-month cardiopulmonary rehabilitation program on cardiorespiratory fitness in long COVID19 patients. Secondary objectives include: to characterize baseline and intervention-related changes in quality of life, functional capacity, functional respiratory capacity, inflammatory profile, coagulation markers, cognitive functions, neurovascular coupling and cortical pulsatility. All participants will have signed a written consent form before taking part in the study. 40 patients who have had COVID-19 with persistent breathlessness and fatigue symptoms after at least 3 months after the diagnosis will be randomly assigned to one of the 2 following study arms : 1/ cardiopulmonary exercise training program; 2/ control group.

COVID-19, cardiorespiratory, fitness, cognition, neurovascular coupling, brain functions, physical exercise, rehabilitation, inflammatory markers, long COVID-19, cortical pulsatility

This clinical trial is a single-blinded study. Research personnel performing the outcome assessments and investigators will be blinded to group allocation.

Cardiopulmonary exercise intervention will include aerobic exercise, resistance and respiratory exercises, three sessions per week for 2 months

Participants will follow a 2-month exercise training program, thrice-weekly trainings. The training sessions will start with a 5-min warmup, followed by an aerobic training (20 min) after which 20-min of resistance/muscular training will take place. The program will end with respiratory exercises and cool down period (10 min). Training will be adapted to individuals' baseline capacity as measured by the baseline cardiorespiratory test. A certified kinesiologist will supervise trainings. Heart rate, oxygen saturation and rating of perceived exertion (Borg Scale, 6-20) will be measured during training sessions.

36-Item Short Form Health Survey (Scale ranges from 0-100, with a higher score indicating a better health status).

State-Trait Anxiety Inventory questionnaire (Score ranges from 20-80, with a higher score indicating higher anxiety).

Perceived Stress Scale questionnaire (Score ranges from 0-4, with 0 no stress,1 mild stress, 3 moderate stress and 4 severe).

Pittsburgh Sleep Quality Index questionnaire (Score ranges from 0-21, with a higher score indicating worse sleep quality). severe).

Montreal Cognitive Assessment (0-30 score, with a higher score indicating a better cognitive functioning).

Changes in brain activity evoked by a N-back task and walking relative to baseline will be assessed by t-statistics maps, computed from variations of [HbO] and [HbR] measured by NIRS at the prefrontal cortex.

Pulsatility will be measured as the normalized difference of relative near-infrared light intensity changes between systole and diastole, using NIRS in the prefrontal cortical region.

Inclusion Criteria: Age between 40 and 80 Individuals infected by the SARS-COV2 virus, with positive PCR diagnosis Still having breathlessness and fatigue at least 3 months after the diagnosis of COVID-19 or patients presenting an increase of 1 point (compared to before infection) on the Modified Medical Research Council scale. Able to perform a maximal cardiopulmonary stress test and exercise training program in accordance with current guidelines on cardiopulmonary rehabilitation. Able to read, understand and sign the information and consent form. Exclusion Criteria: pulmonary embolism diagnosed by scintigraphy Absolute and relative contraindication to exercise stress test and / or exercise training Recent cardiovascular events (cardiac decompensation or angioplasty or cardiac surgery, less than 1 month; valvular disease requiring surgical correction, active myopericarditis, severe ventricular arrhythmias not stabilized under treatment). Kidney failure requiring dialysis heart failure (NYHA III or IV)

Besnier F, Berube B, Malo J, Gagnon C, Gregoire CA, Juneau M, Simard F, L'Allier P, Nigam A, Iglesies-Grau J, Vincent T, Talamonti D, Dupuy EG, Mohammadi H, Gayda M, Bherer L. Cardiopulmonary Rehabilitation in Long-COVID-19 Patients with Persistent Breathlessness and Fatigue: The COVID-Rehab Study. Int J Environ Res Public Health. 2022 Mar 31;19(7):4133. doi: 10.3390/ijerph19074133.