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

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.

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