Exercise intolerance and fatigue are the most common symptoms in patients with chronic COVID after hospital discharge. Muscle deconditioning, dysautonomia, and exercise hyperventilation have been proposed as potential mechanisms contributing to exercise functional capacity limitation in Long-COVID. Along this line, combined exercise training or inspiratory muscle training (IMT) alone have already been demonstrated to be feasible therapeutic options for Long-COVID patients. However, we do not have evidence about the effects of a home-based IMT program for 12-week on peak oxygen consumption (peakVO2). in patients chronic COVID (>3 months) after hospital discharge.

This is a prospective study, blinded for the evaluator, randomized (1:1) to receive standard management alone or combined with a program of IMT that will be carried out in a single center. After randomization, patients will be clinically evaluated. The primary endpoint (peakVO2) will be assessed by cardiopulmonary exercise testing (CPET) at 12-week. Patients with chronic COVID (>3 months) after hospital discharge will be enrolled. A sample size estimation [alfa: 0.05, power: 80%, a 15% loss rate, and at least a delta change of mean peakVO2: +3 mL/kg/min (SD±2.5)] of 26 patients (13 per arm) would be necessary to test our hypothesis.

Exercise intolerance and fatigue are the most common symptoms in patients with chronic COVID after hospital discharge. Muscle deconditioning, dysautonomia, and exercise hyperventilation have been proposed as potential mechanisms contributing to exercise functional capacity limitation in Long-COVID. Along this line, combined exercise training or inspiratory muscle training (IMT) alone have already been demonstrated to be feasible therapeutic options for Long-COVID patients. However, we do not have evidence about the effects of a home-based IMT program for 12-week on peak oxygen consumption (peakVO2). in patients chronic COVID (>3 months) after hospital discharge.

This is a prospective study, blinded for the evaluator, randomized (1:1) to receive standard management alone or combined with a program of IMT that will be carried out in a single center. Patients allocated to the IMT arm will be instructed to train at home twice daily, for 20 minutes each session, using a Threshold inspiratory muscle trainer (Respironics Inc., Parsippany, NJ). They will be instructed by a physiotherapist responsible for training intervention and educated to maintain diaphragmatic breathing during the training period. The subjects will start breathing at a resistance equal to 25% to 30% of their maximal inspiratory mouth pressure (MIP) for 1 week. The respiratory therapist will examine the patients at weekly intervals by checking the diary card and measuring the MIP each time. The resistance will be modified each session according to the 25% to 30% of their MIP measured. After randomization, patients will be clinically evaluated. The primary endpoint (peakVO2) will be assessed by cardiopulmonary exercise testing (CPET) at 12-week. Patients with chronic COVID (>3 months) after hospital discharge will be enrolled. A sample size estimation [alfa: 0.05, power: 80%, a 15% loss rate, and at least a delta change of mean peakVO2: +3 mL/kg/min (SD±2.5)] of 26 patients (13 per arm) would be necessary to test our hypothesis.

Inclusion Criteria:

1. Symptomatic adult patients >18 years old with the previous admission due to SARS-CoV-2 pneumonia
2. > 3-month after discharge
3. The patient provides informed consent

Exclusion Criteria:

1. Inability to perform a maximal baseline exercise test
2. Structural heart disease, valve heart disease, or diastolic dysfunction estimated by 2-dimensional echocardiography
3. Patients with previous ischemic heart disease, heart failure, myocardiopathy, or myocarditis
4. Effort angina or signs of ischemia during CPET
5. Significant primary pulmonary disease, including a history of pulmonary arterial hypertension, chronic thromboembolic pulmonary disease, or chronic obstructive pulmonary disease

(g) Treatment with digitalis, calcium channel blockers, β-blocker or ivabradine (h) Patients with chronic kidney disease (glomerular filtration rate <60mL/min/1.73m2) (i) Patients with pacemakers or previous history of atrial fibrillation; (j) patients with autoimmune, inflammatory or active neoplastic disease k) Anemia (l) Pregnancy.

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Starting 3 months after publication

Data is available upon the reasonable request