5 Meta-Analysis of Cognitive Functioning Following Non-Severe COVID-19 Infection

Abstract

Objective:To effectively diagnose and treat cognitive post-COVID-19 symptoms, it is important to understand objective cognitive difficulties across the range of acute COVID-19 severity. The aim of this meta-analysis is to describe objective neuropsychological test performance in individuals with non-severe (mild/moderate) COVID-19 cases in the post-acute stage of infection (>28 days after initial infection).Participants and Methods:This meta-analysis was pre-registered with Prospero (CRD42021293124) and utilized the PRISMA reporting guidelines, with screening conducted by at least two independent reviewers for all aspects of the screening and data extraction process. Inclusion criteria were established before the article search and were as follows: (1) Studies using adult participants with a probable or formal and documented diagnosis of COVID-19 in the post-acute stage of infection; (2) Studies comparing cognitive functioning using objective neuropsychological tests in one or more COVID-19 groups and a comparison group, or one group designs using tests with normative data; (3) Asymptomatic, mild, or moderate cases of COVID-19. Twenty-seven articles (n=18,202) with three types of study designs and three articles with additional longitudinal data met our full criteria.Results:Individuals with non-severe initial COVID-19 infection demonstrated worse cognitive performance compared to healthy comparison participants (d=-0.412 [95% CI, -0.718, -0.176)], p=0.001). We used metaregression to examine the relationship between both average age of the sample and time since initial COVID-19 infection (as covariates in two independent models) and effect size in studies with comparison groups. There was no significant effect for age (b=-0.027 [95% CI (0.091, 0.038)], p=0.42). There was a significant effect for time since diagnosis, with a small improvement in cognitive performance for every day following initial acute COVID-19 infection (b=0.011 [95% CI (0.0039, 0.0174)], p=0.002). However, those with mild (non-hospitalized) initial COVID-19 infections performed better than did those who were hospitalized for initial COVID-19 infections (d=0.253 [95% CI (0.372, 0.134)], p<0.001). For studies that used normative data comparisons, there was a small, non-significant effect compared to normative data (d=-0.165 [95% CI (-0.333, 0.003)], p=0.055).Conclusions:Individuals who have recovered from non-severe cases of COVID-19 may be at risk for cognitive decline or impairment and may benefit from cognitive health interventions.