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Editorial
. 2021 Jan 25:27:e930886.
doi: 10.12659/MSM.930886.

Selective Neuronal Mitochondrial Targeting in SARS-CoV-2 Infection Affects Cognitive Processes to Induce 'Brain Fog' and Results in Behavioral Changes that Favor Viral Survival

George B Stefano  1 , Radek Ptacek  1 , Hana Ptackova  1 , Anders Martin  1 , Richard M Kream  1
Affiliations
Editorial

Selective Neuronal Mitochondrial Targeting in SARS-CoV-2 Infection Affects Cognitive Processes to Induce 'Brain Fog' and Results in Behavioral Changes that Favor Viral Survival

George B Stefano et al. Med Sci Monit. .

Abstract

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.

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Conflict of interest statement

Conflict of interest

None.

Figures

Figure 1
Figure 1
‘Brain fog’ and COVID-19 targeting for long-term rehabilitation. SARS-CoV-2, which causes COVID-19, can infect the lungs, CNS, gastrointestinal system, and cardiovascular system. With time, widespread infection increases the total viral load in the infected individual. SARS-CoV-2 can integrate its genome into mitochondria to reduce energy metabolism. The brain is especially vulnerable to hypoxia because cognitive neural processes adjust poorly to hypoxic conditions. Hypoxia is also pro-inflammatory. Therefore, as the viral load increases, cognitive impairment and confusion increase, a condition known as ‘brain fog’. This ongoing cascade of neuronal dysfunction is an important factor in understanding the long-term pathogenesis of CNS infection with SARS-CoV-2. Importantly, the behaviors resulting from ‘brain fog’ may increase the spread of SARS-CoV-2. COVID-19 – coronavirus disease 2019; SARS-CoV-2 – severe acute respiratory syndrome coronavirus 2; CNS – central nervous system.
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References

    1. Wang F, Kream RM, Stefano GB. Long-term respiratory and neurological sequelae of COVID-19. Med Sci Monit. 2020;26:e928996. - PMC - PubMed
    1. Chen X, Laurent S, Onur OA, et al. A systematic review of neurological symptoms and complications of COVID-19. J Neurol. 2020;20:1–11. - PMC - PubMed
    1. Pezzini A, Padovani A. Lifting the mask on neurological manifestations of COVID-19. Nat Rev Neurol. 2020;16(11):636–44. - PMC - PubMed
    1. Lau KK, Yu WC, Chu CM, et al. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis. 2004;10(2):342–44. - PMC - PubMed
    1. Tsai LK, Hsieh ST, Chao CC, et al. Neuromuscular disorders in severe acute respiratory syndrome. Arch Neurol. 2004;61(11):1669–73. - PubMed

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