Search

Synopsis Many patients with COVID-19 will experience acute or longer-term neuropsychiatric complications. The neurobiological mechanisms behind these are beginning to emerge, however the neurotropic hypothesis is not strongly supported by clinical data. The inflammatory response to SARS-CoV-2 is likely to be responsible for delirium and other common acute neuropsychiatric manifestations. Vascular abnormalities such as endotheliopathies contribute to stroke and cerebral microbleeds, with their attendant neuropsychiatric sequelae. Longer-term neuropsychiatric syndromes fall into two broad categories: neuropsychiatric deficits occurring after severe (hospitalised) COVID-19, and ‘long COVID’, which occurs in many patients with a milder acute COVID-19 illness.

AIMS: Psychotic-like experiences (PLEs) are common in adolescents. Their persistence may confer increased susceptibility to psychotic disorder. The early evolution of transient to persistent PLEs is not well known. This study aimed to investigate the early persistence of PLEs (over 6-12 months) in a community sample of adolescents and examine baseline and longitudinal associations of early persistent PLEs. METHODS: Five hundred and ninety Year 10 students were administered the community assessment of psychic experiences (CAPE) to measure PLEs at baseline and at follow up 6-12 months later. Persistent PLEs were defined as those present at or above the 90th centile at both time points. Independent variables of depression, psychological distress and functioning were all measured at both baseline and follow up. Self-esteem, personality and suicidality were assessed at follow up. RESULTS: The study found 5.1% of participants had early persistent PLEs. Persistence was associated positively with depression and distress at both time points, neuroticism and openness at baseline and suicidality at follow up. Persistence was negatively associated with functioning at both time points, agreeableness at baseline and self-esteem at follow-up. Only depression remained significantly associated at both time points when accounting for other variables. Thus, depressive symptoms may account for changes in other domains and be a predictor of early PLEs persistence. CONCLUSIONS: These results reinforce the importance of monitoring and assessing PLEs in young people especially when associated with depression. Further research is required to investigate PLE persistence over longer periods with increased measurement intervals.

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.

SUMMARYBackgroundThe 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 withI2. 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=27·4% [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.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 CONTEXTEvidence before this studyNeuropsychiatric 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.

For over 4 months, we have been in the privileged position of witnessing real-time trends in the literature via our weekly curation of The Neurology and Neuropsychiatry of COVID-19 blog.1 There is an emerging recognition of the need to report the severity and outcomes of neurological complications of SARS-CoV-2 infection. Stroke is a rare but well-documented complication, with most prevalence estimates varying slightly around 0.8%.2 It is therefore important to elucidate both those at risk of developing stroke and stratifying those at risk of more severe outcomes when stroke occurs. We were greatly interested to read the letter by Dmytriw et al ,3 which highlighted potential racial disparities in outcomes from ischaemic stroke after COVID-19. Their novel study built on the hypothesis that black and minority ethnic (BAME) individuals have poorer outcomes from COVID-19 in general.4 An editorial commentary by Renieri5 further highlighted the need to elucidate mechanisms that may drive an interaction between stroke and COVID-19 to explain increased mortality in ethnic minorities. Previously also, Katz et al reported that patients with stroke with COVID-19 were more likely to be from a BAME population than patients with stroke without COVID-19. The potential over-representation of BAME individuals in COVID-19 stroke cohorts …