Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19

: The incidence of infections from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), the etiologic agent for coronavirus disease 2019 (COVID-19), has dramatically escalatedfollowing the initial outbreak in China, in late 2019, resulting in a global pandemic withmillions of deaths. Although the majority of infected patients survive, and the rapid advent and deploymentof vaccines have afforded increased immunity against SARS-CoV-2, long-term sequelaeof SARS-CoV-2 infection have become increasingly recognized. These include, but are not limitedto, chronic pulmonary disease, cardiovascular disorders, and proinflammatory-associated neurologicaldysfunction that may lead to psychological and neurocognitive impairment. A major componentof cognitive dysfunction is operationally categorized as “brain fog” which comprises difficultyconcentrating, forgetfulness, confusion, depression, and fatigue. Multiple parameters associatedwith long-term neuropsychiatric sequelae of SARS-CoV-2 infection have been detailed in clinicalstudies. Empirically elucidated mechanisms associated with the neuropsychiatric manifestations ofCOVID-19 are by nature complex, but broad-based working models have focused on mitochondrialdysregulation, leading to systemic reductions of metabolic activity and cellular bioenergeticswithin the CNS structures. Multiple factors underlying the expression of brain fog may facilitate futurepathogenic insults, leading to repetitive cycles of viral and bacterial propagation. Interestingly,diverse neurocognitive sequelae associated with COVID-19 are not dissimilar from those observedin other historical pandemics, thereby providing a broad and integrative perspective on potentialcommon mechanisms of CNS dysfunction subsequent to viral infection. Poor mental health statusmay be reciprocally linked to compromised immune processes and enhanced susceptibility to infectionby diverse pathogens. By extrapolation, we contend that COVID-19 may potentiate the severityof neurological/neurocognitive deficits in patients afflicted by well-studied neurodegenerative disorders,such as Alzheimer's disease and Parkinson’s disease. Accordingly, the prevention, diagnosis,and management of sustained neuropsychiatric manifestations of COVID-19 are pivotal healthcare directives and provide a compelling rationale for careful monitoring of infected patients, asearly mitigation efforts may reduce short- and long-term complications.