Mid and Long-term Neurological and Neuropsychiatric Manifestations of PostCOVID-19 Syndrome: A Meta-analysis

ABSTRACT

Objective: To determine the prevalence of neurological and neuropsychiatric symptoms reported 12 weeks (3 months) or more after acute COVID-19 onset in adults. Background: Neurological and neuropsychiatric symptoms that persist or develop three months after the onset of COVID-19 pose a significant threat to the global healthcare system. These symptoms are yet to be synthesized and quantified via meta-analysis. Design/Methods: A systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1 , 2020 and August 1 , 2021. Studies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence definition of post-COVID-19 syndrome. Additional criteria included reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19. The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported ≥3 months post onset of COVID-19. Results: Of 1,458 articles, 19 studies, encompassing a total of 11,324 patients, were analysed. Overall prevalence for neurological post-COVID-19 symptoms were fatigue (37%, 95% CI 24%- 50%), brain fog (32%, 9%-55%), memory issues (27%, 18%-36%), attention disorder (22%, 10%- 34%), myalgia (18%, 4%-32%), anosmia (12%, 7%-17%), dysgeusia (11%, 4%-17%) and headache (10%, 1%-21%). Neuropsychiatric conditions included sleep disturbances (31%, 18%-43%), anxiety (23%, 13%-33%) and depression (12%, 7%-21%). Neuropsychiatric symptoms substantially increased in prevalence between mid- and long-term follow-up. Compared to non-hospitalised patients, patients hospitalised for acute COVID-19 had reduced risk of anosmia, anxiety, depression, dysgeusia, fatigue, headache, myalgia, and sleep disturbance at three (or more) months post-infection. Conversely, hospital admission was associated with higher frequency of memory issues (OR 1.9, 95% CI 1.4-2.3). Conclusions: Fatigue, brain fog and sleep disturbances appear to be key features of post-COVID19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.