ABSTRACT
BackgroundThe 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. MethodsFor 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 with I2. Subgroup analyses were conducted for COVID-19 hospitalisation, severity, and duration of follow-up. FindingsFrom 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{middle dot}4% [95%CI 21{middle dot}4- 34{middle dot}4%]), followed by fatigue (24{middle dot}4% [17{middle dot}5-32{middle dot}9%]), objective cognitive impairment (20{middle dot}2% [10{middle dot}3-35{middle dot}7%]), anxiety (19{middle dot}1%[13{middle dot}3-26{middle dot}8%]), and post-traumatic stress (15{middle dot}7% [9{middle dot}9-24{middle dot}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{middle dot}6%-98{middle dot}6%). There was little or no evidence of differential symptom prevalence based on hospitalisation status, severity, or follow-up duration. InterpretationNeuropsychiatric 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. FundingJPR 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 CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSNeuropsychiatric 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 studyThis 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. ImplicationsPersistent 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.
Subject(s)
COVID-19ABSTRACT
ObjectivesThere 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. MethodsWe 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. Results13,292 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% [35.2--51.3], n=15,975, 63 studies), weakness (40.0% [27.9--53.5], n=221, 3 studies), fatigue (37.8% [31.6--44.4], n=21,101, 67 studies), dysgeusia (37.2% [30.0--45.3], n=13,686, 52 studies), myalgia (25.1% [19.8--31.3], n=66.268, 76 studies), depression (23.0 % [11.8--40.2], n=43,128, 10 studies), headache (20.7% [95% CI 16.1--26.1], n=64,613, 84 studies), anxiety (15.9% [5.6--37.7], n=42,566, 9 studies) and altered mental status (8.2% [4.4--14.8], n=49,326, 19 studies). Heterogeneity for most clinical manifestations was high. ConclusionsNeurological and neuropsychiatric symptoms of COVID-19 in the pandemics 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.
Subject(s)
COVID-19ABSTRACT
Background A diagnosis of MND takes an average 10-16 months from symptom onset. Early diagnosis is important to access supportive measures to maximise quality of life. The COVID-19 pandemic has caused significant delays in NHS pathways; the majority of GP appointments now occur online with subsequent delays in secondary care assessment. Given the rapid progression of MND, patients may be disproportionately affected resulting in late stage new presentations. We used Monte Carlo simulation to model the pre-COVID-19 diagnostic pathway and then introduced plausible COVID-19 delays. Methods The diagnostic pathway was modelled using gamma distributions of time taken: 1) from symptom onset to GP presentation, 2) for specialist referral, and 3) for diagnosis reached after neurology appointment. We incorporated branches to simulate delays: when patients did not attend their GP and when the GP consultation did not result in referral. An emergency presentation was triggered when diagnostic pathway time was within 30 days of projected median survival. Total time-to-diagnosis was calculated over 100,000 iterations. The pre-COVID-19 model was estimated using published data and the Improving MND Care Survey 2019. We estimated COVID-19 delays using published statistics. Results The pre-COVID model reproduced known features of the MND diagnostic pathway, with a median time to diagnosis of 399 days and predicting 5.2% of MND patients present as undiagnosed emergencies. COVID-19 resulted in diagnostic delays from 558 days when only primary care was 25% delayed, to 915 days when both primary and secondary care were 75%. The model predicted an increase in emergency presentations ranging from 15.4%-44.5%. Interpretations The model suggests the COVID-19 pandemic will result in later-stage diagnoses and more emergency presentations of undiagnosed MND. Late-stage presentations may require rapid escalation to multidisciplinary care. Proactive recognition of acute and late-stage disease with altered service provision will optimise care for people with MND. Funding - This research was supported and funded by a grant from the Reta Lila Weston Trust. NS was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.