Quantitative brain volume differences between COVID-19 patients and non-COVID-19 volunteers: A systematic review

The majority of COVID-19 neuroimaging literature focuses on the acute period after infection and clinically evident lesions. The chronic effects of COVID-19 on brain structure are less well defined. There are inconsistencies in the existing structural neuroimaging studies regarding differences in brain volumes after COVID-19 infection. It was thus our aim to systematically evaluate the structural neuroimaging literature focusing on volumetric differences between patients with COVID-19, and volunteers without COVID-19, at greater than 6 weeks post-infection.

PubMed, Embase, and Scopus were searched in May 2023 with an updated search in September 2024, for studies with a quantitative comparison of brain volumes between COVID-19 patients and non-COVID-19 volunteers with MRI acquired more than 6-weeks after COVID-19. Exclusion criteria included COVID-19 patients selected for the presence of specific symptoms, case reports and case studies, and post-mortem studies. Forwards and backwards citation chasing were performed.

Sixteen studies met inclusion criteria. The majority of studies reported smaller grey matter volumes amongst COVID-19 patients compared to healthy volunteers. However, there were inconsistent findings, with 3 studies reporting larger grey matter volumes in the COVID-19 groups. Additionally, studies with COVID-19 cohorts with more severe presentations, characterized by admission to the hospital or the ICU, were more likely to report smaller grey matter volumes compared to healthy volunteers, than studies that were focused on patients who recovered at home.

A systematic review of the literature indicates that COVID-19 illness severity may explain some of the heterogeneity in brain volume differences between COVID-19 patients and healthy volunteers. More longitudinal follow-up studies are needed to assess the longitudinal course of COVID-19's effects on brain volumes.