Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis

Lavienraj Premraj, Nivedha V Kannapadi, Jack Briggs, Stella M Seal, Denise Battaglini, Jonathon Fanning, Jacky Suen, Chiara Robba, John Fraser, Sung-Min Cho, Lavienraj Premraj, Nivedha V Kannapadi, Jack Briggs, Stella M Seal, Denise Battaglini, Jonathon Fanning, Jacky Suen, Chiara Robba, John Fraser, Sung-Min Cho

Abstract

Importance: 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.

Objective: To determine the prevalence of neurological and neuropsychiatric symptoms reported 12 weeks (3 months) or more after acute COVID-19 onset in adults.

Data sources: A systematic search of PubMed, EMBASE, Web of Science, Google Scholar and Scopus was conducted for studies published between January 1st, 2020 and August 1st, 2021. The systematic review was guided by Preferred Reporting Items for Systematic Review and Meta-Analyses.

Study selection: Studies were included if the length of follow-up satisfied the National Institute for Healthcare Excellence (NICE) definition of post-COVID-19 syndrome (symptoms that develop or persist ≥3 months after the onset of COVID-19). Additional criteria included the reporting of neurological or neuropsychiatric symptoms in individuals with COVID-19.

Data extraction and synthesis: Two authors independently extracted data on patient characteristics, hospital and/or ICU admission, acute-phase COVID-19 symptoms, length of follow-up, and neurological and neuropsychiatric symptoms.

Main outcome(s) and measure(s): The primary outcome was the prevalence of neurological and neuropsychiatric symptoms reported ≥3 months post onset of COVID-19. We also compared post-COVID-19 syndrome in hospitalised vs. non-hospitalised patients, with vs. without ICU admission during the acute phase of infection, and with mid-term (3 to 6 months) and long-term (>6 months) follow-up.

Results: Of 1458 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 frequency 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). Cohorts with >20% of patients admitted to the ICU during acute COVID-19 experienced higher prevalence of fatigue, anxiety, depression, and sleep disturbances than cohorts with <20% of ICU admission.

Conclusions and relevance: Fatigue, cognitive dysfunction (brain fog, memory issues, attention disorder) and sleep disturbances appear to be key features of post-COVID-19 syndrome. Psychiatric manifestations (sleep disturbances, anxiety, and depression) are common and increase significantly in prevalence over time. Randomised controlled trials are necessary to develop intervention strategy to reduce disease burden.

Keywords: COVID-19; ICU; Long-COVID; Long-Haulers; Neuro-COVID-19; PCNS; Post-COVID-19 neurological syndrome; Post-COVID-19 syndrome; SARS-CoV-2.

Copyright © 2022 Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
PRISMA Flow chart, where the total number of patients included refers to those considered in the analysis only.
Fig. 2
Fig. 2
Weighted prevalence of neurological and neuropsychiatric symptoms (95% CI) reported in post-COVID-19 syndrome. Weighted prevalence is presented for outcomes that were reported in at least three studies. REML was then used to determine the weighted frequency (e.g., Supplemental Fig. 2a). Cohort size shows the total number of patients in whom the symptom was assessed. Red dots show weighted frequency. Black lines show 95% confidence intervals.
Fig. 3
Fig. 3
Frequency (proportion) of symptoms reported in post-COVID-19 syndrome. At least three studies were required to provide mid-term and long-term follow-up for frequencies to be displayed. Black dots indicate symptom frequency when assessed between three and six months after acute COVID-19 onset. White dots indicate symptom frequency when assessed at six or more months After acute illness onset.

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Source: PubMed

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