Effect of Pulmonary Rehabilitation and Physical Activity on COVID-19 Long-Term Symptoms (PuReCOVID)

Long COVID affects approximately 10% of COVID-19 survivors, with symptoms persisting beyond the acute phase and impacting multiple organ systems. While some individuals experience mild to moderate illness, others develop severe complications, such as Acute Respiratory Distress Syndrome (ARDS), increasing the risk of long-term pulmonary dysfunction. There is no universally accepted definition of long COVID, but it is often categorized based on symptom duration: post-acute COVID-19 (symptoms persisting beyond three weeks) and chronic COVID-19 (lasting beyond 12 weeks). According to NICE and the Italian National Institute of Health (ISS), long COVID includes symptoms lasting between 4 and 12 weeks (ongoing symptomatic COVID-19) or beyond 12 weeks (post-COVID-19 syndrome), provided they are not attributable to alternative diagnoses.

Common symptoms include fatigue, dyspnea, cough, and chest pain. Some patients recover spontaneously with rest, symptomatic treatment, and gradual physical activity, while others require targeted rehabilitation. Since 80% of breathing effort relies on the diaphragm, long COVID patients often exhibit altered breathing patterns, such as shallow breathing and increased reliance on accessory muscles, leading to dyspnea, fatigue, and inefficient respiration.

Rehabilitation programs have been shown to improve ambulation, hospital discharge rates, and overall recovery in COVID-19 patients, highlighting their potential role in long COVID management. Pulmonary rehabilitation, particularly the Active Cycle of Breathing Technique (ACBT), is a structured method aimed at restoring normal breathing patterns, improving respiratory muscle efficiency, and reducing airway irritation. ACBT consists of controlled breathing, thoracic expansion exercises, forced expiration, and huffing, facilitating airway clearance and optimizing lung function. Given the association between physical inactivity and worse COVID-19 outcomes, rehabilitation strategies incorporating breathing exercises and physical activity may be beneficial.

Pulmonary function studies indicate that Forced Expiratory Volume in 1 second (FEV1) and the FEV1/FVC ratio generally remain within normal limits after COVID-19 recovery, regardless of disease severity. However, impairments in Mid-Expiratory Flow (MEF25-75%) suggest small airway dysfunction (SAD), which appears independent of disease severity but may contribute to persistent respiratory symptoms. Early detection of pulmonary abnormalities is crucial, and Impulse Oscillometry (IOS) is recommended for assessing SAD. Studies indicate that up to 70-90% of symptomatic long COVID patients exhibit persistent SAD up to five months post-infection, emphasizing the need for ongoing lung function monitoring.

This retrospective and prospective study aims to evaluate whether ACBT, combined with moderate daily physical activity, can alleviate symptoms such as cough, dyspnea, and fatigue in long COVID patients. Effectiveness will be assessed using validated clinical scales, including the Leicester Cough Questionnaire (LCQ), the Modified Medical Research Council (mMRC) dyspnea scale, and the Visual Analog Scale (VAS) for fatigue. Additionally, the study will investigate whether respiratory symptoms correlate with SAD, assessed through IOS by analyzing changes in distal airway resistance (R5-R20) and reactance (X5) before and after a six-week rehabilitation period. The rehabilitation protocol involves performing ACBT twice daily at home for six weeks. Clinical and respiratory functional parameters will be assessed before and after the intervention of six weeks. To ensure adherence, patients will receive instructional materials, including video tutorials and augmented reality tools. Additionally, participants will be encouraged to engage in moderate physical activity, aiming for at least 6,000 steps per day, tracked via smartphone applications.

Participants will be monitored over six weeks, with two scheduled visits: an initial baseline assessment (V1) and a follow-up evaluation (V2).

The study protocol was approved by Ethics Committee in the session of 05/07/2022 with protocol. No. 28421 of 07/06/2021.

Data will be collected in a dedicated electronic Clinical Records Form (CRF). The database will be saved on a password-protected company Personal Computer (PC) which will be updated at each visit and used exclusively for scientific research purposes. At the time of enrollment, each patient will receive an alphanumeric code so that any information collected during the study, and in particular sensitive data, is treated in an anonymous manner. Data reporting patients' identifications will only be used to file patients and collect informed consent.

Inclusion criteria

• Male or female adults aged ≥18 years;
• Signed informed consent;
• Patients with long COVID
• Patients with or without ventilatory deficit (FEV1/FVC>/≤70% and FVC>/≤80%)
• Patients reporting at least one of the following symptoms: cough, dyspnea, and fatigue at 24 weeks post-infection

Exclusion criteria

• Patients with other coexisting chronic lung diseases (asthma, fibrosis, bronchiectasis, sarcoidosis, interstitial diseases, pulmonary hypertension)
• Active smoking patients