Alterations in brain functioning, especially in regions associated with cognition, can result from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and are predicted to result in various psychiatric diseases. Recent studies have shown that SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) can directly or indirectly affect the central nervous system (CNS). Therefore, diseases associated with sequelae of COVID-19, or 'long COVID', also include serious long-term mental and cognitive changes, including the condition recently termed 'brain fog'. Hypoxia in the microenvironment of select brain areas may benefit the reproductive capacity of the virus. It is possible that in areas of cerebral hypoxia, neuronal cell energy metabolism may become compromised after integration of the viral genome, resulting in mitochondrial dysfunction. Because of their need for constant high metabolism, cerebral tissues require an immediate and constant supply of oxygen. In hypoxic conditions, neurons with the highest oxygen demand become dysfunctional. The resulting cognitive impairment benefits viral spread, as infected individuals exhibit behaviors that reduce protection against infection. The effects of compromised mitochondrial function may also be an evolutionary advantage for SARS-CoV-2 in terms of host interaction. A high viral load in patients with COVID-19 that involves the CNS results in the compromise of neurons with high-level energy metabolism. Therefore, we propose that selective neuronal mitochondrial targeting in SARS-CoV-2 infection affects cognitive processes to induce 'brain fog' and results in behavioral changes that favor viral propagation. Cognitive changes associated with COVID-19 will have increasing significance for patient diagnosis, prognosis, and long-term care.

• MeSH
• COVID-19 complications   metabolism   physiopathology   psychology   transmission   MeSH
• Energy Metabolism MeSH
• Cognitive Dysfunction metabolism   physiopathology   psychology   MeSH
• Humans MeSH
• Microbial Viability MeSH
• Mitochondria metabolism   MeSH
• Hypoxia, Brain metabolism   physiopathology   psychology   MeSH
• Neurons metabolism   MeSH
• Post-Acute COVID-19 Syndrome MeSH
• Virus Replication MeSH
• SARS-CoV-2 physiology   MeSH
• Viral Load MeSH
• Health Behavior * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Editorial MeSH

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.

• MeSH
• Time Factors MeSH
• COVID-19 complications   epidemiology   immunology   virology   MeSH
• Quality of Life MeSH
• Humans MeSH
• Neurodegenerative Diseases diagnosis   epidemiology   immunology   prevention & control   MeSH
• Pandemics MeSH
• Pulmonary Fibrosis diagnosis   epidemiology   immunology   prevention & control   MeSH
• Lung Injury diagnosis   epidemiology   immunology   prevention & control   MeSH
• Disease Progression MeSH
• SARS-CoV-2 immunology   pathogenicity   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH