Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

25 January 2021: 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 ABCDEF* , Radek Ptacek ABCDEF , Hana Ptackova ABCDEF , Anders Martin ABCDEF , Richard M. Kream ABCDEF

DOI: 10.12659/MSM.930886

Med Sci Monit 2021; 27:e930886

0 Comments

Abstract

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.

Keywords: Hypoxia, Brain, Mitochondria

Conclusions

Recent studies and clinical observations of SARS-CoV-2 infections have yielded insights into the cellular and physiological processes that enhance the ability of the virus to reproduce and spread, including its need for a highly oxygenated microenvironment [28]. Recently, there has been an increased understanding of the possible role of compromised mitochondria in the pathogenesis of SARS-CoV-2 infection. Mitochondrial energy metabolism responds immediately to a hypoxic microenvironment, and mitochondria can serve as mobile sentinel organelles that can act together as an energy delivery system [25]. Given the high energy and oxygenation requirements in neural tissue, mitochondria can serve as indicators of early acute neuronal dysfunction. The relationship between cognitive function, mental health, virus susceptibility, and viral infectivity may be a function of CNS viral load, which increases with time in the case of ‘long-term COVID’. The resulting cognitive impairment benefits viral spread, as infected individuals exhibit reduced anti-infection behaviors (Figure 1). The effects of compromised mitochondrial function may also be an evolutionary advantage for SARS-CoV-2 in terms of its interaction with the host. A high viral load in COVID-19 patients that involves the CNS results in the compromise of neurons with high levels of 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 survival and propagation. Cognitive changes associated with COVID-19 will have increasing significance in patient diagnosis, prognosis, and long-term care. Therefore, there will be an increasing need for support for mental health issues related to COVID-19. Long-term therapeutic strategies for COVID-19 should combine pharmacological agents targeting a chronic ischemic neural pro-inflammatory environment with behavioral activities to restore cognitive function [29,30].

References

1. Wang F, Kream RM, Stefano GB: Long-term respiratory and neurological sequelae of COVID-19: Med Sci Monit, 2020; 26; e928996

2. Chen X, Laurent S, Onur OA: A systematic review of neurological symptoms and complications of COVID-19: J Neurol, 2020; 20; 1-11

3. Pezzini A, Padovani A: Lifting the mask on neurological manifestations of COVID-19: Nat Rev Neurol, 2020; 16(11); 636-44

4. Lau KK, Yu WC, Chu CM: Possible central nervous system infection by SARS coronavirus: Emerg Infect Dis, 2004; 10(2); 342-44

5. Tsai LK, Hsieh ST, Chao CC: Neuromuscular disorders in severe acute respiratory syndrome: Arch Neurol, 2004; 61(11); 1669-73

6. Correa-Palacio AF, Hernandez-Huerta D, Gomez-Arnau J: Affective psychosis after COVID-19 infection in a previously healthy patient: A case report: Psychiatry Res, 2020; 290; 113115

7. Chandra PS, Shiva L, Nagendrappa S: COVID 19 related psychosis as an interface of fears, socio-cultural issues and vulnerability – case report of two women from India: Psychiatry Res, 2020; 290; 113136

8. Mawhinney JA, Wilcock C, Haboubi H, Roshanzamir S: Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode: BMJ Case Rep, 2020; 13(6); e236123

9. Beach SR, Praschan NC, Hogan C: Delirium in COVID-19: A case series and exploration of potential mechanisms for central nervous system involvement: Gen Hosp Psychiatry, 2020; 65; 47-53

10. Epstein D, Andrawis W, Lipsky AM: Anxiety and suicidality in a hospitalized patient with COVID-19 infection: Eur J Case Rep Intern Med, 2020; 7(5); 001651

11. Chen N, Zhou M, Dong X: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study: Lancet, 2020; 395(10223); 507-13

12. Zhang Y, Ma ZF: Impact of the COVID-19 pandemic on mental health and quality of life among local residents in Liaoning province, China: A cross-sectional study: Int J Environ Res Public Health, 2020; 17(7); 2381

13. Ptacek R, Ptackova H, Martin A, Stefano GB: Psychiatric manifestations of COVID-19 and their social significance: Med Sci Monit, 2020; 26; e930340

14. Croall ID, Hoggard N, Aziz I: Brain fog and non-coeliac gluten sensitivity: Proof of concept brain MRI pilot study: PLoS One, 2020; 15(8); e0238283

15. Calabrese F, Pezzuto F, Fortarezza F: Pulmonary pathology and COVID-19: Lessons from autopsy. The experience of European Pulmonary Pathologists: Virchows Arch, 2020; 477(3); 359-72

16. Tian S, Xiong Y, Liu H: Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies: Mod Pathol, 2020; 33(6); 1007-14

17. Xu Z, Shi L, Wang Y: Pathological findings of COVID-19 associated with acute respiratory distress syndrome: Lancet Respir Med, 2020; 8(4); 420-22

18. Wu KE, Fazal FM, Parker KR: RNA-GPS Predicts SARS-CoV-2 RNA residency to host mitochondria and nucleolus: Cell Syst, 2020; 11(1); 102-108.e3

19. Shenoy S: Coronavirus (Covid-19) sepsis: Revisiting mitochondrial dysfunction in pathogenesis, aging, inflammation, and mortality: Inflamm Res, 2020; 69(11); 1077-85

20. Singh KK, Chaubey G, Chen JY, Suravajhala P: Decoding SARS-CoV-2 hijacking of host mitochondria in COVID-19 pathogenesis: Am J Physiol Cell Physiol, 2020; 319(2); C258-67

21. Stefano GB, Esch T, Kream RM: Potential Immunoregulatory and antiviral/SARS-CoV-2 activities of nitric oxide: Med Sci Monit, 2020; 26; e925679

22. Stefano GB, Esch T, Kream RM: Behaviorally-mediated entrainment of whole-body metabolic processes: Conservation and evolutionary development of mitochondrial respiratory complexes: Med Sci Monit, 2019; 25; 9306-9

23. Hayakawa K, Bruzzese M, Chou SH: Extracellular mitochondria for therapy and diagnosis in acute central nervous system injury: JAMA Neurol, 2018; 75(1); 119-22

24. Nakamura Y, Park JH, Hayakawa K: Therapeutic use of extracellular mitochondria in CNS injury and disease: Exp Neurol, 2020; 324; 113114

25. Esch T, Stefano GB, Ptacek R, Kream RM: Emerging roles of blood-borne intact and respiring mitochondria as bidirectional mediators of pro- and anti-inflammatory processes: Med Sci Monit, 2020; 26; e924337

26. Esch T, Stefano GB: Proinflammation: A common denominator or initiator of different pathophysiological disease processes: Med Sci Monit, 2002; 8(5); HY1-9

27. Esch T, Stefano GB, Fricchione GL, Benson H: The role of stress in neurodegenerative diseases and mental disorders: Neuro Endocrinol Lett, 2002; 23(3); 199-208

28. Tobin MJ, Laghi F, Jubran A: Why COVID-19 silent hypoxemia is baffling to physicians: Am J Respir Crit Care Med, 2020; 202(3); 356-60

29. Huang L, Ma Q, Li Y: Inhibition of microRNA-210 suppresses pro-inflammatory response and reduces acute brain injury of ischemic stroke in mice: Exp Neurol, 2018; 300; 41-50

30. von Arnim CAF, Bartsch T, Jacobs AH: Diagnosis and treatment of cognitive impairment: Z Gerontol Geriatr, 2019; 52(4); 309-15

SARS-CoV-2/COVID-19

11 January 2022 : Clinical Research  

A Remote Questionnaire-Based Study to Compare Alcohol Use in 1030 Final-Year High School Students in Split-...

Med Sci Monit In Press; DOI: 10.12659/MSM.935567  

08 November 2021 : Database Analysis  

Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Cor...

Med Sci Monit In Press; DOI: 10.12659/MSM.934102  

31 December 2021 : Clinical Research  

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus...

Med Sci Monit 2021; 27:e935075

30 December 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

Med Sci Monit 2021; 27:e935379

In Press

17 Jan 2022 : Clinical Research  

Unveiling the Differences in Biological Properties of Dental Pulp Stem Cells from Normal and Inflamed Pulp:...

Med Sci Monit In Press; DOI: 10.12659/MSM.934511  

14 Jan 2022 : Database Analysis  

Identification of Key Genes Associated with Brain Metastasis from Breast Cancer: A Bioinformatics Analysis

Med Sci Monit In Press; DOI: 10.12659/MSM.935071  

13 Jan 2022 : Review article  

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hyperc...

Med Sci Monit In Press; DOI: 10.12659/MSM.935821  

13 Jan 2022 : Clinical Research  

Effect of Cerebral Microbleeds on Cognitive Function and Quality of Life in Parkinson Disease

Med Sci Monit In Press; DOI: 10.12659/MSM.935026  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

05 Mar 2020 : Clinical Research  

The Effects of Social Support on Sleep Quality of Medical Staff Treating Patients with Coronavirus Disease ...

DOI :10.12659/MSM.923549

Med Sci Monit 2020; 26:e923549

15 Apr 2020 : Clinical Research  

Psychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...

DOI :10.12659/MSM.924171

Med Sci Monit 2020; 26:e924171

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750