The global COVID-19 pandemic, while primarily recognized for its acute respiratory complications, has also caused a multitude of long-term sequelae. Post-Acute Sequelae of SARS-CoV-2 infection (PASC) affects individuals’ functional abilities across various organ systems. Emphasizing the profound impact on disability, the entry examines prolonged symptoms such as fatigue, cognitive dysfunction, respiratory issues, musculoskeletal pain, gastrointestinal disturbances, mental health disorders, and cardiovascular complications like myocarditis. Despite extensive research, substantial gaps remain in fully comprehending the scope of these long-term effects and identifying individuals at greatest risk for chronic disability. The entry draws on a wide array of studies exploring mechanisms behind Long COVID-related disabilities, highlighting immune dysregulation, viral persistence, and systemic inflammation as key drivers. It delves into how Long COVID exacerbates existing disabilities—such as worsening symptoms in individuals with multiple sclerosis, Parkinson’s disease, or chronic obstructive pulmonary disease—and how it leads to new disabilities through persistent and debilitating symptoms. By providing critical insights into the socioeconomic challenges posed by Long COVID, including employment difficulties and increased strain on healthcare systems, the entry underscores the urgent need for targeted interventions, supportive policies, and continued research. It advocates for a comprehensive, multidisciplinary approach to rehabilitation and support, aiming to inform effective healthcare interventions and disability management strategies that can mitigate the long-term impact of the pandemic on vulnerable populations.