68 Subjective Cognitive Functioning Following Non-Severe COVID-19 Acute Infections: A Meta-Analysis

Abstract

Objective:

Emerging evidence suggests that individuals recovering from COVID-19 perceive changes to their cognitive function and psychological health that persist for weeks to months following acute infection. Although there is a strong relationship between initial COVID-19 infection severity and development of prolonged symptoms, there is only a modest relationship between initial COVID-19 severity and self-reported severity of prolonged symptoms. While much of the research has focused on more severe COVID-19 cases, over 90% of COVID-19 infections are classified as mild or moderate. Previous work has found evidence that non-severe COVID-19 infection is associated with cognitive deficits with small-to-medium effect sizes, though patients who were not hospitalized generally performed better on cognitive measures than did those who were hospitalized for COVID-19 infection. As such, it is important to also quantify subjective cognitive functioning in non-severe (mild or moderate) COVID-19 cases. Our meta-analysis examines self-reported cognition in samples that also measured objective neuropsychological performance in individuals with non-severe COVID-19 infections in the post-acute (>28 days) period.

Participants and Methods:

This study’s design was preregistered with PROSPERO (CRD42021293124) and used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist for reporting guidelines. Inclusion criteria were established prior to article searching and required peer-reviewed studies to have (1) used adult participants with a probable or documented diagnosis of non-severe (asymptomatic, mild, or moderate) COVID-19 who were in the post-acute stage (>28 days after initial infection); (2) used objective neuropsychological testing to document cognitive functioning; and (3) include a self-report measure of subjective cognition. At least two independent reviewers conducted all aspects of the screening, reviews, and extraction process. Twelve studies with three types of study design met full criteria and were included (total n=2,744).

Results:

Healthy comparison group comparison: Compared with healthy comparison participants, the post-COVID-19 group reported moderately worse subjective cognition (d=0.546 [95% CI (0.054, 1.038)], p=0.030). Severity comparison: When comparing hospitalized and not hospitalized groups, patients who were hospitalized reported modestly worse subjective cognition (d=-0.241, [95% CI (-0.703, 0.221)], p=0.30), though the difference was not statistically significant. Normative data comparison: When all non-severe groups (mild and moderate; k=12) were compared to the normative comparison groups, there was a large, statistically significant effect (d=-1.06, [95% CI (-1.58, -0.53)], p=0.001) for self-report of worse subjective cognitive functioning.

Conclusions:

There was evidence of subjective report of worse cognitive functioning following non-severe COVID-19 infection. Future work should explore relationships between objective neuropsychological functioning and subjective cognitive difficulties following COVID-19.