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

Abstract

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. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 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 pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I ². Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 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 most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 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 (I ² = 79.6-98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. 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 prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection.

Keywords: COVID-19; Long COVID; chronic COVID syndrome; neuropsychiatry; post-acute sequelae of COVID-19.

Graphical Abstract

Figure 1

PRISMA flowchart.

Figure 2

Forest plots for individual neuropsychiatric symptoms (1–4). Sleep problems, fatigue, objective cognitive dysfunction and anxiety. Symptoms are plotted individually. The point prevalence for individual studies is presented with 95% confidence intervals on the right-hand side of each plot. The pooled prevalence and 95% confidence interval for that symptom is shown at the bottom of each plot.

Figure 3

Forest plots for individual neuropsychiatric symptoms (5–8). PTSD/PTS, subjective cognitive dysfunction, depression and dysosmia.

Figure 4

Forest plots for individual neuropsychiatric symptoms (9–11). Dysgeusia, sensorimotor dysfunction and dizziness or vertigo.

Figure 5

Pooled symptom prevalence by subgroups. Four subgroup analyses are shown (major panels A–D). Within each analysis, symptoms which were eligible for analysis are plotted individually (identified in the right-hand tab on each minor panel). (A) Comparison of pooled prevalence for studies reporting non-hospitalized versus hospitalized samples. (B) Comparison of studies reporting patients who had non-ITU/non-severe versus ITU/critical/severe COVID-19. (C) Comparison of studies reporting duration of follow-up shorter than 12 weeks post-hospital discharge, versus those reporting longer follow-up. (D) Comparison of studies reporting duration of follow-up shorter than 12 weeks since onset of COVID-19 symptoms, versus those reporting longer follow-up.