Objective: This study aimed to evaluate the effectiveness of a multisystem rehabilitation program for Long Covid patients in two different settings.

Design: Randomized controlled trial. Settings: Health resort and home-based. Participants: 72 Long Covid patients. Interventions: Patients were randomly assigned into two groups: Group A (n=36) received health resort intervention, and Group B (n=36) received home-based care. Both groups underwent a 5-week rehabilitation program, involving motor, respiratory, and cognitive exercises, two sessions per week.

Outcomes: Assessments were conducted before (T0) and after treatment (T1), at 3 (T2) and 6 months (T3), including respiratory and physical function, handgrip strength, fatigue, pain, quality of life, psychological function, and satisfaction.

At the outpatient clinics of the Neurorehabilitation Unit of the University Hospital of Padua, 103 patients were initially assessed. Out of these patients, 72 subjects of both genders with medium-to-long-term outcomes following previous infection with the SARS-CoV-2 virus were recruited for this study. Eight patients were excluded from the study due to initial assessments revealing conditions falling under exclusion criteria (1 patient lacked a prior diagnosis with a COVID-19 infection swab, 2 had concurrent tumor pathologies, 3 exhibited systemic inflammation, and 2 had skin infections), and 23 patients chose to undergo a rehabilitation program at a rehabilitative gym instead. Participants were randomly assigned to one of two rehabilitation treatment groups: the group treated at a health resort facility (Group A, n=36) and the group performing the exercise program at home (Group B, n=36). However, 6 patients did not complete follow-up assessments at different time points, resulting in the final evaluation of data collected from 66 patients, with 33 allocated to Group A and 33 to Group B (Fig. 1).

The patient enrollment was conducted between January 2023 and April 2023. Patients in group A underwent a 5-week rehabilitation cycle with two weekly sessions, totaling 10 sessions, in a health resort setting. The patients underwent treatments at two health resort facilities located in the Euganean Basin, Veneto, Italy, equipped with pools of the same depth, size, and water type. Patients in group B underwent a 5-week rehabilitation cycle at home with two weekly sessions, totaling 10 sessions.

At the beginning (T0) and at the end (T1) of the treatment, and during two subsequent follow-up times at 3 months (T2) and 6 months (T3), after the end of the treatment, patients in both groups were evaluated.

The inclusion criteria for the study included the following requirements: age between 18 and 75 years; a previous COVID-19 infection occurring between 6 and 18 months before our initial assessment; negative results in tests for the nucleic acid of the SARS-CoV-2 virus conducted on respiratory samples, such as oropharyngeal swabs; body temperature ≤ 37°C; presence of reduced cardio-respiratory capacity and/or motor deficits caused by the SARS-CoV-2 virus infection; manifestation of possible cognitive symptoms that could not be attributed to other conditions; no participation in cycles of thermal mineral-rich therapy in the six months preceding the study.

Exclusion criteria from the study included: inability to understand and sign the informed consent form; absence of a previous positive detection of nucleic acid of the SARS-CoV-2 virus in tests on respiratory samples; current positivity for the nucleic acid of the SARS-CoV-2 virus in respiratory samples; epilepsy, severe psychiatric disorders, neoplasms, or pregnancy. Moreover, commonly recognized contraindications for health resort treatments, such as skin infections or open wounds, systemic inflammation, heart, liver, respiratory, or kidney failure, and urinary or fecal incontinence, were considered additional exclusion criteria.