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 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 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. 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 most commonly moderate. The most prevalent 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. 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 six months after infection.

Depression, Insomnia and Post-Traumatic Stress Disorder in COVID-19 Survivors: Role of Gender and Impact on Quality of Life

“…Likewise, an early in-person follow-up study in Wuhan, China, found sleep abnormalities to be one of the most reported complications amongst 1733 discharged patients 6 months post-disease onset, affecting roughly 26% of their cohort [ 29 ]. Similar findings were reported in studies across Europe, including France and the U.K. where sleep difficulties affected 30.8% and 24% of survivors, respectively, 3–4 months following symptom onset and hospitalization [ 14 , 36 ].…”

“…Another recently published systematic review including 51 studies (n = 18,917 patients) also reported persistent problems with sleep disturbance (27%), anxiety (19%), depression PTSD (16%), and cognitive impairment (20%). There was little or no evidence of differences in prevalence based on hospitalization status, disease severity or follow-up duration [ 14 ].…”

Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to LONG COVID: a precision nomothetic approach

“…Regardless of whether COVID-19 patients were symptomatic or asymptomatic during the acute phase of illness, 10-20% of them will experience Long COVID symptoms within weeks to months after recovery (Huang, Pinto et al 2021, World Health Organization 2022). Other results show that 80% of the recovered COVID- 19 patients suffer from at least one of the Long COVID symptoms, including fatigue, memory impairment, anxiety and depression (Lopez-Leon, Wegman-Ostrosky et al 2021, Badenoch, Rengasamy et al 2022). Interestingly, the prevalence of Long COVID is not affected by hospitalization status, disease severity, or length of follow-up (Davido, Seang et al 2020, Badenoch, Rengasamy et al 2022).…”

“…Other results show that 80% of the recovered COVID- 19 patients suffer from at least one of the Long COVID symptoms, including fatigue, memory impairment, anxiety and depression (Lopez-Leon, Wegman-Ostrosky et al 2021, Badenoch, Rengasamy et al 2022). Interestingly, the prevalence of Long COVID is not affected by hospitalization status, disease severity, or length of follow-up (Davido, Seang et al 2020, Badenoch, Rengasamy et al 2022).…”

Multi-organ impairment and Long COVID: a 1-year prospective, longitudinal cohort study

“…There have been heterogenous methods to investigate Long COVID, whether qualitative [26][27][28][29][30] or quantitative 7 , or symptom surveys 31 versus cohort studies 4,32 . Most research still focuses on individual organs [33][34][35][36] . The scale of Long COVID burden necessitates action to develop, evaluate and implement evidence-based investigation, treatment and rehabilitation 37 (e.g., STIMULATE-ICP and other studies 4 ).…”