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COVID-19-associated neurological and psychological manifestations

Nature Reviews Disease Primers volume 11, Article number: 91 (2025) Cite this article

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Abstract

Long COVID is an infection-associated chronic condition that typically occurs within 3 months of acute COVID-19 infection in which symptoms are intermittently or continuously present for at least 3 months. Long COVID is estimated to affect between 80 and 400 million people globally, with an incidence of 5–20% in the community and up to 50% among hospitalized patients following acute SARS-CoV-2 infection. Common neuropsychiatric and mental health symptoms of long COVID include memory deficits, executive dysfunction, anxiety, depression, recurring headaches, sleep disturbances, neuropathies, problems with taste and smell, and dizziness that accompanies erratic heart rates and severe post-exertional malaise. Underlying pathophysiological mechanisms includes SARS-CoV-2 viral persistence, herpesvirus reactivation, microbiota dysbiosis, autoimmunity, clotting and endothelial abnormalities, and chronic immune activation. Owing to the variability in the clinical presentation, management must be tailored based on a patient’s presenting symptoms.

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Fig. 1: Risk factors and clinical manifestations of neurocognitive and psychiatric manifestations of COVID-19.
Fig. 2: Proposed pathobiological mechanisms of long COVID.
Fig. 3: Change in functional, cognitive and emotional behaviour with long COVID.

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Acknowledgements

J.E.W. and E.W.E. are supported by NIA 1R01AG085873 and by the Department of Veterans Affairs Geriatric Research, Education and Clinical Center. M.J.P. is supported on K23AI157875 and 1R01NS136197. E.W.E. is supported by the National Institute on Aging (NIA) R01AG058639, NIA 1R01AG085873 and VA Merit 1RX002992. A.I. is supported by the Else Kröner Fresenius Prize for Medical Research 2023, grants from National Institute of Allergy and Infectious Disease (NIAID) R01AI157488, the Howard Hughes Medical Institute Collaborative COVID-19 Initiative, the Howard Hughes Medical Institute Emerging Pathogens Initiative, and the Howard Hughes Medical Institute. C.L.Y. is supported by The Brazilian National Council for Scientific and Technological Development (CNPQ 403307/2021-0, 445340/2024-0, 315953/2021-7). D.D.F. is supported by the Canadian Institutes for Health Research (grant no. 185352, Long COVID Web) and the Schmidt Initiative for Long Covid (SILC-2023-006, LC-Optimize and SILC-2024-004, LC-Revitalize, NCT06928272).

Author information

Authors and Affiliations

  1. Center for Critical Illness, Brain Dysfunction, and Survivorship (CIBS), Vanderbilt University Medical Center, Nashville, TN, USA

    Jo Ellen Wilson & E. Wesley Ely

  2. Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA

    Jo Ellen Wilson

  3. Geriatric Research Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA

    Jo Ellen Wilson & E. Wesley Ely

  4. Kirby Institute, Sydney, New South Wales, Australia

    Deepti Gurdasani

  5. Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria

    Raimund Helbok

  6. Clinical Research Institute of Neuroscience, Johannes Kepler University Linz, Linz, Austria

    Raimund Helbok

  7. Selcuk University Faculty of Medicine, Department of Neurology, Konya, Turkey

    Serefnur Ozturk

  8. Departments of Pediatrics, Physiology & Pharmacology, and Clinical Neurological Sciences, Western University, London, Ontario, Canada

    Douglas D. Fraser

  9. Human Neuroscience Group, University of Belgrade Institute for Medical Research, Belgrade, Serbia

    Saša R. Filipović

  10. Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, CA, USA

    Michael J. Peluso

  11. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA

    Akiko Iwasaki

  12. Howard Hughes Medical Institute, Chevy Chase, MD, USA

    Akiko Iwasaki

  13. Center for Infection and Immunity, Yale University School of Medicine, New Haven, CT, USA

    Akiko Iwasaki

  14. University of Campinas (UNICAMP), Campinas, Brazil

    Clarissa Lin Yasuda

  15. Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil

    Clarissa Lin Yasuda

  16. “Aldo Ravelli” Research Center for Experimental Brain Therapeutics, Department of Health Sciences, Milan University Medical School, Milan, Italy

    Tommaso Bocci & Alberto Priori

  17. Department of Immunology and Inflammation, Imperial College London, London, UK

    Daniel Altmann

  18. School of Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, UK

    Nisreen A. Alwan

  19. University Hospital Southampton NHS Foundation Trust, Southampton, UK

    Nisreen A. Alwan

  20. Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    E. Wesley Ely

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  1. Jo Ellen Wilson
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  2. Deepti Gurdasani
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Contributions

All authors contributed to all sections of the manuscript.

Corresponding author

Correspondence to Jo Ellen Wilson.

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Competing interests

J.E.W. received research support from the Department of Veterans Affairs Office of Rural Health, Ac-Immune, IONIS therapeutics, Bristol Meyers Squibb and Ono therapeutics outside the submitted work. M.J.P. received consulting fees from Gilead Sciences, AstraZeneca, BioVie, Apellis Pharmaceuticals and BioNTech, and research support from Aerium Therapeutics and Shionogi, outside the submitted work. R.H. received grant funding from Fresenius Kabi Germany and Austrian Science Fund; and has received payments or honoraria from BD, Integra, Neuroptics and Zoll, not related to the submitted work. N.A.A. is a Long Covid Kids Charity Champion, is a scientific adviser to the Long Covid Support Charity, and has contributed in an advisory capacity to WHO and the EU Commission’s Expert Panel on effective ways of investing in health meetings in relation to post-COVID-19 conditions. E.W.E. has NIH funding for an ongoing clinical trial of immunomodulation in long COVID for which the JAK–STAT medical intervention is donated by Eli Lilly; E.W.E. has no financial relationship with Eli Lilly and has no stocks or paid consultancies with Eli Lilly. C.L.Y. is supported by CNPQ. D.G., S.O., D.D.F., S.R.F., A.I., T.B., A.P. and D.A. declare no competing interests.

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Nature Reviews Disease Primers thanks N. Babel; D. Marazziti; and B. Michael, who co-reviewed with R. Matthews, for their contribution to the peer review of this work.

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Wilson, J.E., Gurdasani, D., Helbok, R. et al. COVID-19-associated neurological and psychological manifestations. Nat Rev Dis Primers 11, 91 (2025). https://doi.org/10.1038/s41572-025-00674-7

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