Background: Post-COVID syndrome is a complex condition affecting patients after SARS-CoV-2 infection. It is characterized by fatigue, pain, reduced resilience, and quality of life. Severe cases resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), associated with post-exertional malaise (PEM). Due to the unknown etiology and lack of curative options, multimodal therapy offers a particularly promising approach to symptom management.

Methods: This qualitative interview study was part of a mixed-methods project conducted in 2022–2023, which investigated the effects of a multimodal integrative day clinic approach (MICOM day clinic) on the symptoms and general well-being of individuals with Post-COVID syndrome. The aim of the qualitative sub-study was to gain a deeper understanding of the individual perspectives of patients on their experiences of the illness and the perceived changes reported by 20 intervention group participants after completing the 11-week (66-h) multimodal program. Interview data had been analyzed based on reflexive thematic analysis using MAXQDA software.

Results: Participants reported significant impairments in daily life and work capacity, accompanied by high psychological burden. The multimodal program led to improvements in physical and mental symptoms, overall well-being, and self-efficacy. Patients also reported long-term lifestyle changes in areas such as nutrition, stress regulation, and performance-oriented physical activity.

Conclusion: Post-COVID syndrome poses ongoing challenges for individuals and healthcare systems. Multimodal integrative treatment can effectively reduce symptoms, enhance coping strategies, and promote sustainable self-care.

Clinical trial registration: Clinicaltrials.gov, identifier NCT05630378.