COVID-19-associated neurological and psychological manifestations

Jo Ellen Wilson^{1

2

3}, Deepti Gurdasani⁴, Raimund Helbok^{5

6}, Serefnur Ozturk⁷, Douglas D Fraser⁸, Saša R Filipović⁹, Michael J Peluso¹⁰, Akiko Iwasaki^{11

12

13}, Clarissa Lin Yasuda^{14

15}, Tommaso Bocci¹⁶, Alberto Priori¹⁶, Daniel Altmann¹⁷, Nisreen A Alwan^{18

19}, E Wesley Ely^{20

21

22}

Affiliations

¹ Center for Critical Illness, Brain Dysfunction, and Survivorship (CIBS), Vanderbilt University Medical Center, Nashville, TN, USA. jo.e.wilson@vumc.org.
² Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. jo.e.wilson@vumc.org.
³ Geriatric Research Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA. jo.e.wilson@vumc.org.
⁴ Kirby Institute, Sydney, New South Wales, Australia.
⁵ Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.
⁶ Clinical Research Institute of Neuroscience, Johannes Kepler University Linz, Linz, Austria.
⁷ Selcuk University Faculty of Medicine, Department of Neurology, Konya, Turkey.
⁸ Departments of Pediatrics, Physiology & Pharmacology, and Clinical Neurological Sciences, Western University, London, Ontario, Canada.
⁹ Human Neuroscience Group, University of Belgrade Institute for Medical Research, Belgrade, Serbia.
¹⁰ Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, CA, USA.
¹¹ Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
¹² Howard Hughes Medical Institute, Chevy Chase, MD, USA.
¹³ Center for Infection and Immunity, Yale University School of Medicine, New Haven, CT, USA.
¹⁴ University of Campinas (UNICAMP), Campinas, Brazil.
¹⁵ Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil.
¹⁶ "Aldo Ravelli" Research Center for Experimental Brain Therapeutics, Department of Health Sciences, Milan University Medical School, Milan, Italy.
¹⁷ Department of Immunology and Inflammation, Imperial College London, London, UK.
¹⁸ School of Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, UK.
¹⁹ University Hospital Southampton NHS Foundation Trust, Southampton, UK.
²⁰ Center for Critical Illness, Brain Dysfunction, and Survivorship (CIBS), Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Geriatric Research Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA.
²² Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

PMID: 41444262
DOI: 10.1038/s41572-025-00674-7

Review

COVID-19-associated neurological and psychological manifestations

Jo Ellen Wilson et al. Nat Rev Dis Primers. 2025.

. 2025 Dec 24;11(1):91.

doi: 10.1038/s41572-025-00674-7.

Authors

Affiliations

¹ Center for Critical Illness, Brain Dysfunction, and Survivorship (CIBS), Vanderbilt University Medical Center, Nashville, TN, USA. jo.e.wilson@vumc.org.
² Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. jo.e.wilson@vumc.org.
³ Geriatric Research Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA. jo.e.wilson@vumc.org.
⁴ Kirby Institute, Sydney, New South Wales, Australia.
⁵ Department of Neurology, Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria.
⁶ Clinical Research Institute of Neuroscience, Johannes Kepler University Linz, Linz, Austria.
⁷ Selcuk University Faculty of Medicine, Department of Neurology, Konya, Turkey.
⁸ Departments of Pediatrics, Physiology & Pharmacology, and Clinical Neurological Sciences, Western University, London, Ontario, Canada.
⁹ Human Neuroscience Group, University of Belgrade Institute for Medical Research, Belgrade, Serbia.
¹⁰ Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, CA, USA.
¹¹ Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
¹² Howard Hughes Medical Institute, Chevy Chase, MD, USA.
¹³ Center for Infection and Immunity, Yale University School of Medicine, New Haven, CT, USA.
¹⁴ University of Campinas (UNICAMP), Campinas, Brazil.
¹⁵ Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil.
¹⁶ "Aldo Ravelli" Research Center for Experimental Brain Therapeutics, Department of Health Sciences, Milan University Medical School, Milan, Italy.
¹⁷ Department of Immunology and Inflammation, Imperial College London, London, UK.
¹⁸ School of Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, UK.
¹⁹ University Hospital Southampton NHS Foundation Trust, Southampton, UK.
²⁰ Center for Critical Illness, Brain Dysfunction, and Survivorship (CIBS), Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Geriatric Research Education and Clinical Center (GRECC), Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA.
²² Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

PMID: 41444262
DOI: 10.1038/s41572-025-00674-7

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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Conflict of interest statement

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.

References

1. Yong, S. J. & Liu, S. Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies. Rev. Med. Virol. 32, e2315 (2022). - PubMed - DOI
1. Sivan, M. & Taylor, S. NICE guideline on long covid. BMJ 371, m4938 (2020). - PubMed - DOI
1. Soriano, J. B. et al. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect. Dis. 22, e102–e107 (2022). - PubMed - DOI
1. Ballering, A. V., van Zon, S. K. R., Olde Hartman, T. C., Rosmalen, J. G. M. & Lifelines Corona Research, I. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet 400, 452–461 (2022). - PubMed - PMC - DOI
1. Al-Aly, Z. et al. Long COVID science, research and policy. Nat. Med. 30, 2148–2164 (2024). - PubMed - DOI

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COVID-19-associated neurological and psychological manifestations

Affiliations

COVID-19-associated neurological and psychological manifestations

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

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LinkOut - more resources

Full Text Sources

Medical

Miscellaneous