Title:Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric
Sequelae of COVID-19
Volume: 20
Issue: 6
Author(s): George B. Stefano*, Pascal Büttiker, Simon Weissenberger, Radek Ptacek, Fuzhou Wang, Tobias Esch, Thomas V. Bilfinger, Jiri Raboch and Richard M. Kream
Affiliation:
- Center for Cognitive and Molecular Neuroscience, First Faculty of Medicine, Charles University, Prague, Czech Republic
Keywords:
Central nervous system, neuroinflammation, neuropsychiatric disease, mitochondria, microglia, SARS-CoV-2, COVID-19, long COVID, cognitive impairment, brain fog, depression, anxiety.
Abstract: 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 escalated
following the initial outbreak in China, in late 2019, resulting in a global pandemic with
millions of deaths. Although the majority of infected patients survive, and the rapid advent and deployment
of vaccines have afforded increased immunity against SARS-CoV-2, long-term sequelae
of SARS-CoV-2 infection have become increasingly recognized. These include, but are not limited
to, chronic pulmonary disease, cardiovascular disorders, and proinflammatory-associated neurological
dysfunction that may lead to psychological and neurocognitive impairment. A major component
of cognitive dysfunction is operationally categorized as “brain fog” which comprises difficulty
concentrating, forgetfulness, confusion, depression, and fatigue. Multiple parameters associated
with long-term neuropsychiatric sequelae of SARS-CoV-2 infection have been detailed in clinical
studies. Empirically elucidated mechanisms associated with the neuropsychiatric manifestations of
COVID-19 are by nature complex, but broad-based working models have focused on mitochondrial
dysregulation, leading to systemic reductions of metabolic activity and cellular bioenergetics
within the CNS structures. Multiple factors underlying the expression of brain fog may facilitate future
pathogenic insults, leading to repetitive cycles of viral and bacterial propagation. Interestingly,
diverse neurocognitive sequelae associated with COVID-19 are not dissimilar from those observed
in other historical pandemics, thereby providing a broad and integrative perspective on potential
common mechanisms of CNS dysfunction subsequent to viral infection. Poor mental health status
may be reciprocally linked to compromised immune processes and enhanced susceptibility to infection
by diverse pathogens. By extrapolation, we contend that COVID-19 may potentiate the severity
of 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 health
care directives and provide a compelling rationale for careful monitoring of infected patients, as
early mitigation efforts may reduce short- and long-term complications.