Emerging Knowledge of the Neurobiology of COVID-19

doi:10.1016/j.psc.2021.11.001

Review

. 2022 Mar;45(1):29-43.

doi: 10.1016/j.psc.2021.11.001. Epub 2021 Nov 11.

Emerging Knowledge of the Neurobiology of COVID-19

Matthew Butler¹, Benjamin Cross², Danish Hafeez³, Mao Fong Lim⁴, Hamilton Morrin⁵, Emma Rachel Rengasamy⁶, Tom Pollak⁷, Timothy R Nicholson⁷

Affiliations

¹ Institute of Psychiatry, Psychology and Neuroscience, King's College, 16 De Crespigny Park, SE5 8AF London. Electronic address: Matthew.butler@kcl.ac.uk.
² East Lancashire Hospitals NHS Trust, Casterton Ave, Burnley, BB10 2PQ.
³ School of Medical Sciences, The University of Manchester, Oxford Rd, Manchester, M13 9PL, UK.
⁴ Cambridge University Hospitals NHS Foundation Trust, Hills Rd, Cambridge, CB2 0QQ, UK.
⁵ Maidstone & Tunbridge Wells NHS Trust, Tonbridge Rd, Royal Tunbridge Wells, TN2 4QJ, UK.
⁶ Cwm Taf Morgannwg University Health Board, Ynysmeurig House, Navigation Park, Abercynon, CF45 4SN, UK.
⁷ Institute of Psychiatry, Psychology and Neuroscience, King's College, 16 De Crespigny Park, SE5 8AF London.

PMID: 35219440
PMCID: PMC8580843
DOI: 10.1016/j.psc.2021.11.001

Review

Emerging Knowledge of the Neurobiology of COVID-19

Matthew Butler et al. Psychiatr Clin North Am. 2022 Mar.

. 2022 Mar;45(1):29-43.

doi: 10.1016/j.psc.2021.11.001. Epub 2021 Nov 11.

Authors

Matthew Butler¹, Benjamin Cross², Danish Hafeez³, Mao Fong Lim⁴, Hamilton Morrin⁵, Emma Rachel Rengasamy⁶, Tom Pollak⁷, Timothy R Nicholson⁷

Affiliations

¹ Institute of Psychiatry, Psychology and Neuroscience, King's College, 16 De Crespigny Park, SE5 8AF London. Electronic address: Matthew.butler@kcl.ac.uk.
² East Lancashire Hospitals NHS Trust, Casterton Ave, Burnley, BB10 2PQ.
³ School of Medical Sciences, The University of Manchester, Oxford Rd, Manchester, M13 9PL, UK.
⁴ Cambridge University Hospitals NHS Foundation Trust, Hills Rd, Cambridge, CB2 0QQ, UK.
⁵ Maidstone & Tunbridge Wells NHS Trust, Tonbridge Rd, Royal Tunbridge Wells, TN2 4QJ, UK.
⁶ Cwm Taf Morgannwg University Health Board, Ynysmeurig House, Navigation Park, Abercynon, CF45 4SN, UK.
⁷ Institute of Psychiatry, Psychology and Neuroscience, King's College, 16 De Crespigny Park, SE5 8AF London.

PMID: 35219440
PMCID: PMC8580843
DOI: 10.1016/j.psc.2021.11.001

Abstract

Many patients with COVID-19 will experience acute or longer-term neuropsychiatric complications. The neurobiological mechanisms behind these are beginning to emerge; however, the neurotropic hypothesis is not strongly supported by clinical data. The inflammatory response to SARS-CoV-2 is likely to be responsible for delirium and other common acute neuropsychiatric manifestations. Vascular abnormalities such as endotheliopathies contribute to stroke and cerebral microbleeds, with their attendant neuropsychiatric sequelae. Longer-term neuropsychiatric syndromes fall into 2 broad categories: neuropsychiatric deficits occurring after severe (hospitalized) COVID-19 and "long COVID," which occurs in many patients with a milder acute COVID-19 illness.

Keywords: COVID-19; Delirium; Long COVID; Neurobiology; Neuropsychiatry; SARS-CoV-2.

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Dix E, Roy K. Dix E, et al. Psychiatr Clin North Am. 2022 Dec;45(4):625-637. doi: 10.1016/j.psc.2022.07.009. Epub 2022 Jul 6. Psychiatr Clin North Am. 2022. PMID: 36396269 Free PMC article. Review.
Cognitive domains affected post-COVID-19; a systematic review and meta-analysis.
Fanshawe JB, Sargent BF, Badenoch JB, Saini A, Watson CJ, Pokrovskaya A, Aniwattanapong D, Conti I, Nye C, Burchill E, Hussain ZU, Said K, Kuhoga E, Tharmaratnam K, Pendered S, Mbwele B, Taquet M, Wood GK, Rogers JP, Hampshire A, Carson A, David AS, Michael BD, Nicholson TR, Paddick SM, Leek CE. Fanshawe JB, et al. Eur J Neurol. 2025 Jan;32(1):e16181. doi: 10.1111/ene.16181. Epub 2024 Feb 20. Eur J Neurol. 2025. PMID: 38375608 Free PMC article.
Multi-target drugs for the treatment of cognitive impairment and fatigue in post-COVID syndrome: focus on Ginkgo biloba and Rhodiola rosea.
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Just When We Thought That COVID Was Over: A Systematic Review.
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References

1. Worldometer. COVID-19 CORONAVIRUS PANDEMIC. https://www.worldometers.info/coronavirus/ Available at: Accessed July 22, 2021.
1. Butler M., Pollak T.A., Rooney A.G., et al. Neuropsychiatric complications of covid-19. BMJ. 2020:m3871. doi: 10.1136/bmj.m3871. - DOI - PubMed
1. Rogers J.P., Chesney E., Oliver D., et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7(7):611–627. doi: 10.1016/S2215-0366(20)30203-0. - DOI - PMC - PubMed
1. Rogers JP, Watson C, Badenoch J, et al. The neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives. Published online February 26, 2021. doi:10.1101/2021.02.24.21252335 - PubMed
1. Mondal R., Ganguly U., Deb S., et al. Meningoencephalitis associated with COVID-19: a systematic review. J Neurovirol. 2021;27(1):12–25. doi: 10.1007/s13365-020-00923-3. - DOI - PMC - PubMed

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[1] Worldometer. COVID-19 CORONAVIRUS PANDEMIC. https://www.worldometers.info/coronavirus/ Available at: Accessed July 22, 2021.

[2] Worldometer. COVID-19 CORONAVIRUS PANDEMIC. https://www.worldometers.info/coronavirus/ Available at: Accessed July 22, 2021.

[3] Butler M., Pollak T.A., Rooney A.G., et al. Neuropsychiatric complications of covid-19. BMJ. 2020:m3871. doi: 10.1136/bmj.m3871. - DOI - PubMed

[4] Butler M., Pollak T.A., Rooney A.G., et al. Neuropsychiatric complications of covid-19. BMJ. 2020:m3871. doi: 10.1136/bmj.m3871. - DOI - PubMed

[5] Rogers J.P., Chesney E., Oliver D., et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7(7):611–627. doi: 10.1016/S2215-0366(20)30203-0. - DOI - PMC - PubMed

[6] Rogers J.P., Chesney E., Oliver D., et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020;7(7):611–627. doi: 10.1016/S2215-0366(20)30203-0. - DOI - PMC - PubMed

[7] Rogers JP, Watson C, Badenoch J, et al. The neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives. Published online February 26, 2021. doi:10.1101/2021.02.24.21252335 - PubMed

[8] Rogers JP, Watson C, Badenoch J, et al. The neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives. Published online February 26, 2021. doi:10.1101/2021.02.24.21252335 - PubMed

[9] Mondal R., Ganguly U., Deb S., et al. Meningoencephalitis associated with COVID-19: a systematic review. J Neurovirol. 2021;27(1):12–25. doi: 10.1007/s13365-020-00923-3. - DOI - PMC - PubMed

[10] Mondal R., Ganguly U., Deb S., et al. Meningoencephalitis associated with COVID-19: a systematic review. J Neurovirol. 2021;27(1):12–25. doi: 10.1007/s13365-020-00923-3. - DOI - PMC - PubMed

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Emerging Knowledge of the Neurobiology of COVID-19

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Emerging Knowledge of the Neurobiology of COVID-19

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