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Background: COVID-19 survivors who were hospitalised continue to experience long-term multisystemic sequelae and symptoms, impacting their health-related quality of life (HRQoL). The complexity of post-COVID-19 conditions underscores the importance of adopting a multidisciplinary, patient-centric approach to ensure ongoing care. This study aims to assess HRQoL and post-COVID symptoms in a cohort of severe COVID-19 survivors depending on their participation in a multidisciplinary programme., Methods: This prospective study was conducted in a post-COVID clinic staffed by a multidisciplinary team (physical rehabilitator, nutritionist, psychologist, including experts in pulmonary rehabilitation, nutrition, psychology and others). Subjects over 18 years old who were hospitalised due to severe COVID-19 during the acute phase and had attended the post-COVID clinic within the first 3 months following discharge were included. Subjects who were unable or unwilling to provide informed consent to participate in the protocol were excluded. Linear mixed-effect models were employed to examine changes in 12-Item Short-Form Health Survey (SF-12) component scores. The resolution of post-COVID symptom clusters was compared using the Cox model., Results: A total of 730 patients were included, with a mean±sd age of 55.78±15.43 years; 60.55% were male and 90.62% required mechanical ventilation during hospitalisation. Programme attendants demonstrated improved SF-12 physical and mental component scores at 3 and 12 months. A reduction in the prevalence of post-COVID symptoms was observed in both groups, with greater reductions in those attending the programme., Conclusion: Our study showed that patients enrolled on the multidisciplinary programme experienced improvements in fatigue, musculoskeletal, gastrointestinal, neuropsychiatric and respiratory symptoms, along with enhanced SF-12 mental and physical component scores., Competing Interests: Conflict of interest: All the authors have nothing to disclose., (Copyright ©The authors 2024.)