Since the initial reports of coronavirus disease 2019 (COVID-19) in China in late 2019, infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have spread rapidly, resulting in a global pandemic that has caused millions of deaths. Initially, the large number of infected people required the direction of global healthcare resources to provide supportive care for the acutely ill population in an attempt to reduce mortality. While clinical trials for safe and effective antiviral agents are ongoing, and vaccine development programs are being accelerated, long-term sequelae of SARS-CoV-2 infection have become increasingly recognized and concerning. Although the upper and lower respiratory tracts are the main sites of entry of SARS-CoV-2 into the body, resulting in COVID-19 pneumonia as the most common presentation, acute lung damage may be followed by pulmonary fibrosis and chronic impairment of lung function, with impaired quality of life. Also, increasing reports have shown that SARS-CoV-2 infection involves the central nervous system (CNS) and the peripheral nervous system (PNS) and directly or indirectly damages neurons, leading to long-term neurological sequelae. This review aims to provide an update on the mechanisms involved in the development of the long-term sequelae of SARS-CoV-2 infection in the 3 main areas of lung injury, neuronal injury, and neurodegenerative diseases, including Alzheimer disease, Parkinson disease, and multiple sclerosis, and highlights the need for patient monitoring following the acute stage of infection with SARS-CoV-2 to provide a rationale for the prevention, diagnosis, and management of these potential long-term sequelae.