The global COVID-19 crisis, caused by severe acute respiratory syndrome coronavirus 2, is well-known for its long COVID symptoms, which can persist for weeks, months, or even years after the initial illness. COVID-19 affects multiple organs throughout the body, including the brain, heart, lungs, liver, endocrine system, and kidneys, with both acute and long-term impacts. Children and adolescents have been significantly affected by the pandemic, experiencing challenges such as virtual learning, increased screen time, reduced physical activity, unhealthy eating habits, and limited opportunities for interaction and sports. According to the US Government’s Centers for Disease Control and Prevention, individuals with certain disabilities are at a greater risk of developing complications from respiratory viruses. These individuals often face barriers to accessing healthcare services and should be prioritized for masks, vaccines, and COVID-19 antivirals whenever possible. Social distancing and self-isolation are also recommended for their protection. This entry explores COVID-19 pathophysiology, immune dysregulation, and epidemiology. It also examines the impact of COVID-19 on both healthy individuals and those with disabilities across all age groups. Additionally, it addresses how persistent symptoms affect the physical, social, and psychological well-being of young people. Furthermore, this entry discusses risk factors and management strategies for certain long-term sequelae.