COVID-19 and cognitive impairment: From evidence to SARS-CoV-2 mechanism

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) primarily manifests as respiratory dysfunction. However, emerging evidence suggests SARS-CoV-2 can invade the brain, leading to cognitive impairment (CI). It may spread to other brain regions through transsynaptic neurons, including the olfactory, optic, and vagus nerves. Moreover, it may invade the central nervous system through blood transmission or the lymphatic system. This review summarizes the neuroimaging evidence from clinical and imaging studies of COVID-19-associated CIs, including magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography-computed tomography. The mechanisms underlying COVID-19-associated CIs are currently being actively investigated. They include nonimmune effects, such as viral proteins, tissue hypoxia, hypercoagulability, and pathological changes in neuronal cells, and immune effects, such as microglia and astrocyte activation, peripheral immune cell infiltration, blood-brain barrier impairment, cytokine network dysregulation, and intestinal microbiota. Inflammation is the central feature. Both central and systemic inflammation may cause acute and persistent neurological changes, and existing evidence indicates that inflammation underlies the elevated risk of Alzheimer's disease. Finally, potential therapeutic options for COVID-19-associated CIs are discussed. In-depth research into the pathological mechanisms is still needed to help develop new therapies.