Gender Differences in the Recovery Rate Following PR in Patients With Long COVID-19

Study Overview
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Brief Summary
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The goal of this retrospective analysis is to compare the magnitude of improvement in respiratory and peripheral muscle strength, following the completion of a hybrid pulmonary rehabilitation programme, in men and women with long COVID-19 syndrome. The main question it aims to answer is the following: • does gender limits the effects of a hybrid pulmonary rehabilitation programme on respiratory and peripheral muscle strength?

Detailed Description
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As of January 2023, more than 500 million people have been affected by Severe Acute Respiratory Distress Syndrome-Coronavirus-2 (SARS-COV-2) globally. In Greece, since January 2020 there have been more than 5 million confirmed cases of COVID-19 and more than 35,000 deaths. Based on this data, it seems that the majority of patients recover (even those requiring hospital admission) but present with persistent symptoms at least three months after the acute illness, a condition defined as 'Long COVID-19'. The most commonly reported symptoms include long-standing fatigue, dyspnoea, muscle and joint pain, sleep disturbances, short-term memory loss and brain fog. This syndrome affects a large group of patients, and according to World Health Organisation it imposes a great burden on the healthcare systems worldwide. Consequently, it is important to identify preventable risk factors for 'Long COVID-19' in order to address the complex needs of these patients and reduce the prevalence of this new long-term condition. According to the Post-hospitalisation COVID-19 study (PHOSP-COVID) which has included adults with COVID-19 discharged from United Kingdom hospitals, the main risk factors associated with worse recovery at 1 year involved obesity, need for invasive mechanical ventilation during the acute illness and female sex. Other studies evaluating the prevalence of 'Long COVID-19' in the two sexes found that female patients were more likely to have one or more symptoms 12 months following the acute phase of the disease. Despite the fact that lengths of hospital and ICU stay were reduced in women compared to men, female sex proved to be an independent risk factor for the development of ongoing symptoms, among which were fatigue, dyspnoea, muscle aches and generalised weakness. The autoimmune hypothesis could account for the higher incidence of 'Long COVID-19' syndrome in women. According to this hypothesis, the immune response for both genetic and hormonal factors is stronger in women compared to men and hence autoimmune reactions are more prevalent in women. Guidelines have been published suggesting the implementation of pulmonary rehabilitation (PR) programmes for the management of patients with 'Long COVID-19' syndrome. According to recently published systematic reviews, pulmonary rehabilitation is beneficial for patients with long COVID-19 syndrome in terms of quality of life, muscle strength, walking capacity and sit-to-stand performance. Whether reduced recovery prognosis and long-lasting ongoing symptoms in women adversely affect the outcome of rehabilitation is still unknown. This is an important issue for healthcare systems when considering management strategies for people with 'Long COVID-19' syndrome. Furthermore, tele-rehabilitation programmes are feasible and effective in improving physical capacity, quality of life and symptoms in adult survivors of COVID-19. Accordingly, the present study looked into the effect of a hybrid rehabilitation programme (including out-patient and home-based sessions) on physical and mental health outcomes in previously hospitalised women and men with 'Long COVID-19' syndrome. It was hypothesised that the magnitude of improvement in women would be less compared to men.

Official Title
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Gender Differences in the Recovery Rate Following a Hybrid Pulmonary Rehabilitation Programme in Patients With Long COVID-19 Syndrome

Conditions
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Post Acute COVID-19 Syndrome

Intervention / Treatment
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* Other: Out-patient Pulmonary Rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalisation due to Sars-COV-2 infection. Presence of persistence fatigue assessed via FACIT questionnaire. Exclusion Criteria: Exclusion criteria include presence of any of the following list within 3 months prior to informed consent: participation in another clinical trial occurrence of myocardial infarction hospitalisation for unstable angina stroke coronary artery bypass graft (CABG) percutaneous coronary intervention (PCI) implantation of a cardiac resynchronisation therapy device (CRTD) active treatment for cancer or other malignant disease uncontrolled congestive heart disease (NYHA class >3) acute psychosis or major psychiatric disorders or continued substance abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Men with long COVID-19 syndrome<br>Patients were male adults (>18 years), with persistent symptoms more than 3 months since the acute phase of the COVID-19. | Other: Out-patient Pulmonary Rehabilitation<br>* Pulmonary Rehabilitation (PR) programme consisting of 30 minutes interval aerobic exercise on cycle ergometers at 100% of peak work rate (WRpeak) and resistance exercises for the upper body. Dyspnoea and leg discomfort were recorded on the modified 1-10 Borg scale, whereas heart rate (HR) and oxygen saturation (SpO2%) were monitored by a pulse oximeter. Based on symptoms of breathlessness and fatigue reported at the end of each session, the exercise intensity was increased by 5-10% of the baseline WRpeak in the next session. The remote 24 home-based PR sessions consisted of 30 minutes walking with an individualised target of steps, recorded via the mobile app installed in the patients' mobile phone. The steps, leg discomfort and dyspnoea were reported by the patient via a physical activity diary on a weekly basis. If dyspnoea and fatigue were both <4 at the Borg scale the weekly target of steps was increased by 5-10% by the assessors.<br>|
| Women with long COVID-19 syndrome<br>Patients were women adults (>18 years), with persistent symptoms more than 3 months since the acute phase of the COVID-19. | Other: Out-patient Pulmonary Rehabilitation<br>* Pulmonary Rehabilitation (PR) programme consisting of 30 minutes interval aerobic exercise on cycle ergometers at 100% of peak work rate (WRpeak) and resistance exercises for the upper body. Dyspnoea and leg discomfort were recorded on the modified 1-10 Borg scale, whereas heart rate (HR) and oxygen saturation (SpO2%) were monitored by a pulse oximeter. Based on symptoms of breathlessness and fatigue reported at the end of each session, the exercise intensity was increased by 5-10% of the baseline WRpeak in the next session. The remote 24 home-based PR sessions consisted of 30 minutes walking with an individualised target of steps, recorded via the mobile app installed in the patients' mobile phone. The steps, leg discomfort and dyspnoea were reported by the patient via a physical activity diary on a weekly basis. If dyspnoea and fatigue were both <4 at the Borg scale the weekly target of steps was increased by 5-10% by the assessors.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | Degree of fatigue will be assessed via the Functional Assessment of Chronic Illness Therapy questionnaire | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quadriceps muscle strength | Quadriceps muscle strength will be reported as maximum strength in kg | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Handgrip muscle strength | Handgrip muscle strength will be reported as maximum strength in kg | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Inspiratory muscle strength | Inspiratory muscle strength will be reported as maximum strength in centimeters water | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Expiratory muscle strength | Expiratory muscle strength will be reported as maximum strength in centimeters water | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Dyspnoea | Dyspnoea will be assessed via completion of modified Medical Research Council Dyspnoea Scale questionnaire. The score ranges from 0-4. The greater the score, the worse the dyspnoea levels | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Emotional status | Emotional status will be assessed via completion of the Hospital Anxiety and Depression. Scale questionnaire. The score ranges from 0-21 for each component (anxiety and depression). The higher the score, the higher the levels of anxiety and depression. | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Symptoms | Symptoms will be assessed via completion of the Chronic Obstructive Pulmonary Disease Assessment Tool questionnaire. The score ranges from 0-40 points. The higher the score, the worse the prognosis. | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Self-reported quality of life | Self-reported quality of life will be assessed via completion of the EuroQol-5Dimension-5Levels questionnaire. | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Post traumatic stress disorder (PTSD) | PTSD will be assessed via completion of the Impact Event Scale-Revised questionnaire.The total score ranges from 0-88. The higher the score, the higher the levels of PTSD | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Six minute walk distance covered | The distance that patients cover during the six minute walk test. | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Short Physical Performance Buttery test (SPPB) | SPPB is a series of test including balance, 4 meter walk and 5 sit-to-stand repetitions. The test assess the functional capacity of the patients. | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Level of daily physical activity | Level of daily physical activity will be reported as steps per day the week prior the initiation of the intervention and one week following the completion of the intervention. | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Exercise tolerance | Exercise tolerance will be assessed by performing a cardiopulmonary exercise test. | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 
| Cardiac function | Cardiac function will be assessed via a resting echocardiography | Prior and following the completion of a 3 month pulmonary rehabilitation programme (At 0 and at 3 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-Acute COVID-19 Syndrome, Pulmonary Rehabilitation, Muscle strength, Quality of life