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.

• Klíčová slova
• COVID-19, Central nervous system, SARS-CoV-2, anxiety, brain fog, cognitive impairment, depression, long COVID, microglia, mitochondria, neuroinflammation, neuropsychiatric disease,
• MeSH
• centrální nervový systém MeSH
• COVID-19 * komplikace   MeSH
• lidé MeSH
• neurodegenerativní nemoci * MeSH
• pandemie MeSH
• progrese nemoci MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Long COVID, in which disease-related symptoms persist for months after recovery, has led to a revival of the discussion of whether neuropsychiatric long-term symptoms after viral infections indeed result from virulent activity or are purely psychological phenomena. In this review, we demonstrate that, despite showing differences in structure and targeting, many viruses have highly similar neuropsychiatric effects on the host. Herein, we compare severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus 1 (HIV-1), Ebola virus disease (EVD), and herpes simplex virus 1 (HSV-1). We provide evidence that the mutual symptoms of acute and long-term anxiety, depression and post-traumatic stress among these viral infections are likely to result from primary viral activity, thus suggesting that these viruses share neuroinvasive strategies in common. Moreover, it appears that secondary induced environmental stress can lead to the emergence of psychopathologies and increased susceptibility to viral (re)infection in infected individuals. We hypothesize that a positive feedback loop of virus-environment-reinforced systemic responses exists. It is surmised that this cycle of primary virulent activity and secondary stress-induced reactivation, may be detrimental to infected individuals by maintaining and reinforcing the host's immunocompromised state of chronic inflammation, immunological strain, and maladaptive central-nervous-system activity. We propose that this state can lead to perturbed cognitive processing and promote aversive learning, which may manifest as acute, long-term neuropsychiatric illness.

• Klíčová slova
• HIV-1, SARS virus, interoception, neuropsychiatry, virus latency,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• Klíčová slova
• Blood-brain-barrier, SARS-CoV-2, neuroinvasion, viral reservoir,
• Publikační typ
• časopisecké články MeSH

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 komplikace   metabolismus   patofyziologie   psychologie   přenos   MeSH
• energetický metabolismus MeSH
• kognitivní dysfunkce metabolismus   patofyziologie   psychologie   MeSH
• lidé MeSH
• mikrobiální viabilita MeSH
• mitochondrie metabolismus   MeSH
• mozková hypoxie metabolismus   patofyziologie   psychologie   MeSH
• neurony metabolismus   MeSH
• postakutní syndrom COVID-19 MeSH
• replikace viru MeSH
• SARS-CoV-2 fyziologie   MeSH
• virová nálož MeSH
• zdravé chování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• úvodníky MeSH