Persistent neuropsychiatric symptoms after COVID-19: a systematic review and meta-analysis
Authors: Badenoch James B. , Rengasamy Emma R. , Watson Cameron J. , Jansen Katrin , Chakraborty Stuti , Sundaram Ritika D. , Hafeez Danish , Burchill Ella , Saini Aman , Thomas Lucretia , Cross Benjamin , Hunt Camille K. , Conti Isabella , Ralovska Sylvia , Hussain Zain , Butler Matthew , Pollak Thomas A. , Koychev Ivan , Michael Benedict D. , Holling Heinz , Nicholson Timothy R. , Rogers Jonathan P. , Rooney Alasdair G. ,   for the SARS-CoV-Neuro Collaboration
Published: May 2021

Background

The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19.

Methods

For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750) we searched PubMed, EMBASE, CINAHL and PsycINFO to 20th February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection, and in control groups where available. For each study a minimum of two authors extracted summary data. For each symptom we calculated a primary pooled prevalence using generalised linear mixed models. Heterogeneity was measured withI2. Subgroup analyses were conducted for COVID-19 hospitalisation, severity, and duration of follow-up.

Findings

From 2,844 unique titles we included 51 studies (n=18,917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14-182 days). Study quality was generally moderate. The most frequent neuropsychiatric symptom was sleep disturbance (pooled prevalence=27·4% [95%CI 21·4- 34·4%]), followed by fatigue (24·4% [17·5-32·9%]), objective cognitive impairment (20·2% [10·3-35·7%]), anxiety (19·1%[13·3-26·8%]), and post-traumatic stress (15·7% [9·9-24·1%]). Only two studies reported symptoms in control groups, both reporting higher frequencies in Covid-19 survivors versus controls. Between-study heterogeneity was high (I2=79·6%-98·6%). There was little or no evidence of differential symptom prevalence based on hospitalisation status, severity, or follow-up duration.

Interpretation

Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing, but indicates a particularly high frequency of insomnia, fatigue, cognitive impairment, and anxiety disorders in the first six months after infection.

Funding

JPR is supported by the Wellcome Trust (102186/B/13/Z).

IK is funded through the NIHR (Oxford Health Biomedical Research Facility, Development and Skills Enhancement Award) and the Medical Research Council (Dementias Platform UK and Deep and Frequent Phenotyping study project grants).

HH is funded by the German Research Foundation (DFG, Grant: HO 1286/16-1). The funders played no role in the design, analysis or decision to publish.

RESEARCH IN CONTEXT

Evidence before this study

Neuropsychiatric symptoms like cognitive impairment, fatigue, insomnia, depression and anxiety can be highly disabling. Recently there has been increasing awareness of persistent neuropsychiatric symptoms after COVID-19 infection, but a systematic synthesis of these symptoms is not available. In this review we searched five databases up to 20th February 2021, to establish the pooled prevalence of individual neuropsychiatric symptoms up to six months after COVID-19.

Added value of this study

This study establishes which of a range of neuropsychiatric symptoms are the most common after COVID-19. We found high rates in general, with little convincing evidence that these symptoms lessen in frequency during the follow-up periods studied.

Implications

Persistent neuropsychiatric symptoms are common and appear to be limited neither to the post-acute phase, nor to recovery only from severe COVID-19. Our results imply that health services should plan for high rates of requirement for multidisciplinary services (including neurological, neuropsychiatric and psychological management) as populations recover from the COVID-19 pandemic.