Neuropsychiatric Burden of SARS-CoV-2: A Review of Its Physiopathology, Underlying Mechanisms, and Management Strategies

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2025 Jan 8

PMID 39772122

Authors

Aliteia-Maria Pacnejer

Anca Butuca

Carmen Maximiliana Dobrea

Anca Maria Arseniu

Adina Frum

Felicia Gabriela Gligor

Rares Arseniu

Razvan Constantin Vonica

Andreea Loredana Vonica-Tincu

Cristian Oancea

Cristina Mogosan

Ioana Rada Popa Ilie

Claudiu Morgovan

Cristina Adriana Dehelean

Affiliations

Soon will be listed here.

Abstract

The COVID-19 outbreak, caused by the SARS-CoV-2 virus, was linked to significant neurological and psychiatric manifestations. This review examines the physiopathological mechanisms underlying these neuropsychiatric outcomes and discusses current management strategies. Primarily a respiratory disease, COVID-19 frequently leads to neurological issues, including cephalalgia and migraines, loss of sensory perception, cerebrovascular accidents, and neurological impairment such as encephalopathy. Lasting neuropsychological effects have also been recorded in individuals following SARS-CoV-2 infection. These include anxiety, depression, and cognitive dysfunction, suggesting a lasting impact on mental health. The neuroinvasive potential of the virus, inflammatory responses, and the role of angiotensin-converting enzyme 2 (ACE2) in neuroinflammation are critical factors in neuropsychiatric COVID-19 manifestations. In addition, the review highlights the importance of monitoring biomarkers to assess Central Nervous System (CNS) involvement. Management strategies for these neuropsychiatric conditions include supportive therapy, antiepileptic drugs, antithrombotic therapy, and psychotropic drugs, emphasizing the need for a multidisciplinary approach. Understanding the long-term neuropsychiatric implications of COVID-19 is essential for developing effective treatment protocols and improving patient outcomes.

References

Del Rey A, Balschun D, Wetzel W, Randolf A, Besedovsky H . A cytokine network involving brain-borne IL-1β, IL-1ra, IL-18, IL-6, and TNFα operates during long-term potentiation and learning. Brain Behav Immun. 2013; 33:15-23. DOI: 10.1016/j.bbi.2013.05.011. View

Ibrahim Ismail I, Salama S . A systematic review of cases of CNS demyelination following COVID-19 vaccination. J Neuroimmunol. 2021; 362:577765. PMC: 8577051. DOI: 10.1016/j.jneuroim.2021.577765. View

Galea I . The blood-brain barrier in systemic infection and inflammation. Cell Mol Immunol. 2021; 18(11):2489-2501. PMC: 8481764. DOI: 10.1038/s41423-021-00757-x. View

Behnood S, Shafran R, Bennett S, Zhang A, OMahoney L, Stephenson T . Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies. J Infect. 2021; 84(2):158-170. PMC: 8604800. DOI: 10.1016/j.jinf.2021.11.011. View

Zheng M, Karki R, Williams E, Yang D, Fitzpatrick E, Vogel P . TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nat Immunol. 2021; 22(7):829-838. PMC: 8882317. DOI: 10.1038/s41590-021-00937-x. View

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

Sadowski J, Klaudel T, Rombel-Bryzek A, Buldak R . Cognitive dysfunctions in the course of SARS‑CoV‑2 virus infection, including NeuroCOVID, frontal syndrome and cytokine storm (Review). Biomed Rep. 2024; 21(1):103. PMC: 11117100. DOI: 10.3892/br.2024.1791. View

Li Y, Bai W, Hashikawa T . The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020; 92(6):552-555. PMC: 7228394. DOI: 10.1002/jmv.25728. View

Liu N, Zhang F, Wei C, Jia Y, Shang Z, Sun L . Prevalence and predictors of PTSS during COVID-19 outbreak in China hardest-hit areas: Gender differences matter. Psychiatry Res. 2020; 287:112921. PMC: 7102622. DOI: 10.1016/j.psychres.2020.112921. View

10.

Cooper S, Boyle E, Jefferson S, Heslop C, Mohan P, Mohanraj G . Role of the Renin-Angiotensin-Aldosterone and Kinin-Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID. Int J Mol Sci. 2021; 22(15). PMC: 8347967. DOI: 10.3390/ijms22158255. View

11.

Crunfli F, Carregari V, Veras F, Silva L, Nogueira M, Antunes A . Morphological, cellular, and molecular basis of brain infection in COVID-19 patients. Proc Natl Acad Sci U S A. 2022; 119(35):e2200960119. PMC: 9436354. DOI: 10.1073/pnas.2200960119. View

12.

Aksunger N, Vernot C, Littman R, Voors M, Meriggi N, Abajobir A . COVID-19 and mental health in 8 low- and middle-income countries: A prospective cohort study. PLoS Med. 2023; 20(4):e1004081. PMC: 10079130. DOI: 10.1371/journal.pmed.1004081. View

13.

Liu N, Tan J, Liu L, Wang Y, Hua L, Qian Q . Genetic Predisposition Between COVID-19 and Four Mental Illnesses: A Bidirectional, Two-Sample Mendelian Randomization Study. Front Psychiatry. 2021; 12:746276. PMC: 8564104. DOI: 10.3389/fpsyt.2021.746276. View

14.

Webb B, Peltan I, Jensen P, Hoda D, Hunter B, Silver A . Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study. Lancet Rheumatol. 2020; 2(12):e754-e763. PMC: 7524533. DOI: 10.1016/S2665-9913(20)30343-X. View

15.

Jarius S, Pache F, Kortvelyessy P, Jelcic I, Stettner M, Franciotta D . Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients. J Neuroinflammation. 2022; 19(1):19. PMC: 8771621. DOI: 10.1186/s12974-021-02339-0. View

16.

Ramani A, Muller L, Ostermann P, Gabriel E, Abida-Islam P, Muller-Schiffmann A . SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J. 2020; 39(20):e106230. PMC: 7560208. DOI: 10.15252/embj.2020106230. View

17.

Fu J, Zhou B, Zhang L, Balaji K, Wei C, Liu X . Expressions and significances of the angiotensin-converting enzyme 2 gene, the receptor of SARS-CoV-2 for COVID-19. Mol Biol Rep. 2020; 47(6):4383-4392. PMC: 7224351. DOI: 10.1007/s11033-020-05478-4. View

18.

Xie D, He M, Hu X . Microglia/macrophage diversities in central nervous system physiology and pathology. CNS Neurosci Ther. 2019; 25(12):1287-1289. PMC: 7154592. DOI: 10.1111/cns.13257. View

19.

Brunkhorst R, Pfeilschifter W, Foerch C . Astroglial proteins as diagnostic markers of acute intracerebral hemorrhage-pathophysiological background and clinical findings. Transl Stroke Res. 2013; 1(4):246-51. DOI: 10.1007/s12975-010-0040-6. View

20.

Watanabe M, Nakamura Y, Michalak Z, Isobe N, Barro C, Leppert D . Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD. Neurology. 2019; 93(13):e1299-e1311. DOI: 10.1212/WNL.0000000000008160. View