COVID-19-Associated Encephalopathy (COVEP): Basic Aspects of Neuropathology

Abstract

SARS-CoV-2, a member of the betacoronavirus group and causative agent of COVID-19, is a virus affecting multiple systems, not only the respiratory. One of the systems affected by the virus is the central nervous system, with neuropathological studies reporting a wide set of morphological phenomena—neuroinflammation, vascular and blood-brain barrier alterations, neurodegeneration, and accelerated aging, while contradicting data is present on the direct neuroinvasive potential of the virus and active viral replication within neurons. The depicted changes, other than an acute effect (which may contribute to the death of the patient) also have chronic sequelae in the context of post-COVID syndrome cognitive impediments, sleep, and mood disorders. The following chapter describe the basic neuropathological aspects of SARS-CoV-2 as based on the present evidence in scientific literature and propose the term COVEP—COVID-associated encephalopathy—to unite the undisputed effects of the infection on nervous system morphology and function.

Histomorphological Aspects of SARS-CoV-2-Induced Hippocampal Damage: A Case Series

“…The first of the disputed properties of the virus when it comes to the CNS is that of neuroinvasiveness -the ability of the infectious agent to enter the nervous system; by itself, this mechanism does not always lead to pathological changes such as neurovirulence, with and without the possibility of changes in homeostasis (21,27,28). Multiple studies have reported different results regarding detecting viral particles within the CNS, with varying analysis methods (29)(30)(31)(32).…”

“…Biomed Rev 34, 2023 COVID-19 and the hippocampus the native inflammatory cells can damage the neurons rather than the viral agent itself (21,27,37).…”

“…Further, several studies have shown that in cellular culture, the viral particle has entry and replication mechanisms within human neurons, resulting in accelerated neuronal aging and depletion of stem cell properties (21,(38)(39)(40)(41)(42). Suppose these results are proven to be reproducible in vitro.…”

“…The development of COVID-19-Associated Encephalopathy (COVEP) is a widely discussed topic based on varying degrees of evidence and mechanisms for its development (21). To date, COVEP is supported broadly by endothelial-induced changes.…”

“…Furthermore, the chronic sequels of the disease are yet to be appropriately studied and evaluated in the context of the post-infectious specter, referred to as post-COVID syndrome (15)(16)(17)(18). One of the most commonly reported such sequelae is the so-called "brain fog" -loss of concentration, learning difficulties, and confusion (16,(19)(20)(21). Herein, we set out to evaluate the effects of the virus on the central nervous system (CNS), primarily focusing on the dentate gyrus of the hippocampus in a series of autopsy cases.…”