Abstract
BACKGROUND: Persistent symptoms after acute COVID-19, formally recognized as post-COVID-19 condition (PCC), are prevalent and disabling. The World Health Organization has emphasized early, multidisciplinary rehabilitation using accessible and hybrid care models. However, no standard protocol currently exists, and few studies have evaluated digital formats in this context. OBJECTIVE: To examine the effects of two digital rehabilitation formats-immersive virtual reality (IVR) and a self-guided online program-on cognitive and functional outcomes in individuals with PCC. METHODS: The study used a nonrandomized, quasiexperimental pre-post design. We enrolled 172 adults with PCC into a 12-week multimodal program combining cognitive training, physical activity, and mindfulness; participants chose IVR or an online self-guided program, and usual-care controls were recruited at a separate site. Outcomes were assessed before and after across cognitive, psychological, lifestyle, functional, and quality-of-life domains. RESULTS: Significant group-by-time interactions were observed across multiple domains. IVR was associated with improvements in global cognition, immediate recall, recognition memory, and response inhibition. The online intervention showed improvements in verbal recognition, mindfulness, and perceived health-related quality of life. Additional outcomes showed significant group-by-time interactions without postintervention differences, indicating differential trajectories over time rather than discrete between-group effects. CONCLUSIONS: Both IVR and online multimodal interventions were associated with domain-specific cognitive and functional benefits in individuals with PCC. These findings support the potential value of multicomponent rehabilitation approaches, while highlighting that some effects reflect differential trajectories rather than definitive postintervention group differences. STUDY REGISTRATION: www.ClinicalTrials.gov, identifier NCT05846126 (date of registration 04 May 2023).