Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis

Giussani G 1 , Westenberg E 2 , Garcia-Azorin D 3 , Bianchi E 1 , Yusof Khan AHK 4 , Allegri RF 5 Show all authors , Atalar AÇ 6 , Baykan B 7 , Crivelli L 5 , Fornari A 8 , Frontera JA 9 , Guekht A 10 , Helbok R 11 , Hoo FK 4 , Kivipelto M 12 , Leonardi M 8 , Lopez Rocha AS 12 , Mangialasche F 12 , Marcassoli A 8 , Özdag Acarli AN 13 , Ozge A 14 , Prasad K 15 , Prasad M 16 , Sviatskaia E 17 , Thakur K 18 , Vogrig A 19 , Leone M 1 , Winkler AS 2 , Global COVID-19 Neuro Research Coalition

Affiliations 

  • 1 Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
  • 2 Department of Neurology, Center for Global Health, School of Medicine and Health, Technical University of Munich, Munich, Germany
  • 3 Department of Neurology, Hospital Clínico Universitario Valladolid, Valladolid, Spain
  • 4 Department of Neurology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
  • 5 Department of Cognitive Neurology, Fleni, Buenos Aires, Argentina
  • 6 Department of Neurology, Kanuni Sultan Süleyman Education and Research Hospital, Istanbul, Turkey
  • 7 Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
  • 8 Neurology, Public Health, Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
  • 9 Department of Neurology, NYU Grossman School of Medicine, New York, New York, USA
  • 10 Moscow Research and Clinical Center for Neuropsychiatry and Russian National Research Medical University, Moscow, Russian Federation
  • 11 Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
  • 12 Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden
  • 13 Department of Neurology, Ermenek State Hospital, Karaman, Turkey
  • 14 Mersin University School of Medicine, Mersin, Turkey
  • 15 Department of Neurology, Fortis Hospital, New Delhi, India
  • 16 Clinical Research and Epidemiology, Institute of Liver and Biliary Sciences, New Delhi, India
  • 17 Suicide Research and Prevention Department, Moscow Research and Clinical Center for Neuropsychiatry, Moscow, Russian Federation
  • 18 Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York, USA
  • 19 Clinical Neurology, Santa Maria Della Misericordia University Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy
Neuroepidemiology, 2024;58(2):120-133.
PMID: 38272015 DOI: 10.1159/000536352

Abstract

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points.

METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times.

RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence.

DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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