Potential Prion Involvement in Long COVID-19 Neuropathology, Including Behavior

Abstract

Prion' is a term used to describe a protein infectious particle responsible for several neurodegenerative diseases in mammals, e.g., Creutzfeldt-Jakob disease. The novelty is that it is protein based infectious agent not involving a nucleic acid genome as found in viruses and bacteria. Prion disorders exhibit, in part, incubation periods, neuronal loss, and induce abnormal folding of specific normal cellular proteins due to enhancing reactive oxygen species associated with mitochondria energy metabolism. These agents may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation. Interestingly, some of these behavioral changes also occur in COVID-19 and mechanistically include mitochondrial damage caused by SARS-CoV-2 and subsequenct production of reactive oxygen species. Taken together, we surmise, in part, long COVID may involve the induction of spontaneous prion emergence, especially in individuals susceptible to its origin may thus explain some of its manesfestions post-acute viral infection.

Keywords: COVID-19; Confusion; Depression; Long COVID; Mitochondria; Prion; Prion disorders; SARS-CoV-2.

Fig. 1

Hypothetical mechanistic illustration of prion and SARS-CoV-2 mitochondrial targeting. Prions are infectious proteinaceous particles that have been functionally associated with the progression of major human neurodegenerative disorders such as Creutzfeldt-Jakob disease. Empirically elucidated modes of actions of infectious prions include multiple inhibitory patterns adversely affecting normative neural communication as well as initiation of apoptotic or necrotic neural damage. Furthermore, a likely mechanism of prion-related neural dysfunction may also involve aberrant restitution of native conformation of abnormally folded cellular proteins. These pathophysiological effects may be potentially due to loss of normative proteasome functioning due to enhanced reactive oxygen species associated with compromised mitochondria energy metabolism. Infectious prion diseases may also induce memory, personality and movement abnormalities as well as depression, confusion and disorientation. Interestingly, some of these same behavioral sequelae have also been observed to occur subsequent to COVID-19 and may also share pathogenic mitochondrial damage caused by SARS-CoV-2 infection with subsequent production of ROS or RNS. Taken together, we speculate that pathophysiological effects of long COVID may involve the induction of spontaneous production of infectious prion species. Interestingly, mitochondria may represent the central focus of both induced disorders