Persistent neuropsychiatric symptoms after COVID-19: a systematic review and meta-analysis

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 with I2. Subgroup analyses were conducted for COVID-19 hospitalisation, severity, and duration of follow-up. Results: 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. Conclusion: 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.