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

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 three, six, nine and twelve-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 three 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 metal 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 6,545 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 three-month follow-up the pooled prevalence of fatigue, cognitive impairment and sleep disorders was still 20% and higher. At six- and nine-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia and headache to further increase in prevalence. At twelve-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 one-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 twelve-month follow-up time-point, more robust data is needed to confirm this trend