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Meta-Analysis
. 2021 Sep;92(9):932-941.
doi: 10.1136/jnnp-2021-326405. Epub 2021 Jun 3.

Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

Jonathan P Rogers  1   2 , Cameron J Watson  3 , James Badenoch  4 , Benjamin Cross  5 , Matthew Butler  6 , Jia Song  7 , Danish Hafeez  8 , Hamilton Morrin  9 , Emma Rachel Rengasamy  10 , Lucretia Thomas  11 , Silviya Ralovska  12 , Abigail Smakowski  2 , Ritika Dilip Sundaram  13 , Camille Kaitlyn Hunt  14 , Mao Fong Lim  15 , Daruj Aniwattanapong  6   16 , Vanshika Singh  17 , Zain Hussain  18 , Stuti Chakraborty  19 , Ella Burchill  20 , Katrin Jansen  21 , Heinz Holling  21 , Dean Walton  22 , Thomas A Pollak  6 , Mark Ellul  22   23   24 , Ivan Koychev  25   26 , Tom Solomon  22   23 , Benedict Daniel Michael  22   23   24 , Timothy R Nicholson  6 , Alasdair G Rooney  27
Affiliations
Meta-Analysis

Neurology and neuropsychiatry of COVID-19: a systematic review and meta-analysis of the early literature reveals frequent CNS manifestations and key emerging narratives

Jonathan P Rogers et al. J Neurol Neurosurg Psychiatry. 2021 Sep.

Abstract

There is accumulating evidence of the neurological and neuropsychiatric features of infection with SARS-CoV-2. In this systematic review and meta-analysis, we aimed to describe the characteristics of the early literature and estimate point prevalences for neurological and neuropsychiatric manifestations.We searched MEDLINE, Embase, PsycINFO and CINAHL up to 18 July 2020 for randomised controlled trials, cohort studies, case-control studies, cross-sectional studies and case series. Studies reporting prevalences of neurological or neuropsychiatric symptoms were synthesised into meta-analyses to estimate pooled prevalence.13 292 records were screened by at least two authors to identify 215 included studies, of which there were 37 cohort studies, 15 case-control studies, 80 cross-sectional studies and 83 case series from 30 countries. 147 studies were included in the meta-analysis. The symptoms with the highest prevalence were anosmia (43.1% (95% CI 35.2% to 51.3%), n=15 975, 63 studies), weakness (40.0% (95% CI 27.9% to 53.5%), n=221, 3 studies), fatigue (37.8% (95% CI 31.6% to 44.4%), n=21 101, 67 studies), dysgeusia (37.2% (95% CI 29.8% to 45.3%), n=13 686, 52 studies), myalgia (25.1% (95% CI 19.8% to 31.3%), n=66 268, 76 studies), depression (23.0% (95% CI 11.8% to 40.2%), n=43 128, 10 studies), headache (20.7% (95% CI 16.1% to 26.1%), n=64 613, 84 studies), anxiety (15.9% (5.6% to 37.7%), n=42 566, 9 studies) and altered mental status (8.2% (95% CI 4.4% to 14.8%), n=49 326, 19 studies). Heterogeneity for most clinical manifestations was high.Neurological and neuropsychiatric symptoms of COVID-19 in the pandemic's early phase are varied and common. The neurological and psychiatric academic communities should develop systems to facilitate high-quality methodologies, including more rapid examination of the longitudinal course of neuropsychiatric complications of newly emerging diseases and their relationship to neuroimaging and inflammatory biomarkers.

Keywords: COVID-19; clinical neurology; meta-analysis; psychiatry; systematic reviews.

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Conflict of interest statement

Competing interests: JPR has received payment from the Alberta Psychiatric Association for a lecture and has held one unpaid advisory meeting with representatives from Promentis Pharmaceuticals regarding drug development. LT is in receipt of a bursary as part of the Royal College of Psychiatrists PsychStar scheme. By winning a prize from the Royal College of Psychiatrists, she has received prize money and free attendance at a meeting. She is President of the University of Birmingham Psychiatry Society. IK has been supported by the Medical Research Council through Dementias Platform UK and by the National Institute for Health Research (NIHR) through the Oxford Health Biomedical Research Centre. He has been a medical advisor to Mantrah and Sharp Therapeutics, digital technology start-ups. He holds stock options in Sharp Therapeutics. TS is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (grant nos. IS-HPU-1112-10117 and NIHR200907), NIHR Programme Grant for Applied Research (no. RP-PG-0108-10,048), NIHR Global Health Research Group on Brain Infections (no. 17/63/110), and the European Union’s Horizon 2020 research and innovation programme ZikaPLAN (Preparedness Latin America Network), grant agreement no. 734584. He receives royalties from Oxford University Press, Elsevier, Liverpool University Press and Cambridge University Press. He is a consultant for the MHRA Vaccine Benefit Risk Expert Working Group. He filed for a patent on a test for bacterial meningitis based on a blood test (no. GB1606537.7 14 April 2016). He was on the Data Safety Monitoring Committee of the GSK Study to Evaluate the Safety and Immunogenicity of a Candidate Ebola Vaccine in Children GSK3390107A (ChAd3 EBO-Z) vaccine. He chaired the Siemens Healthineers Clinical Advisory Board (1) Data Safety Monitoring Board: Study of Ebola vaccine ChAd3-EBO-Z-Commercial entity. He holds shares in Medefer Solutions. BDM has received payment for a lecture for Valneva.

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