Longitudinal Monitoring of Brain Volume Changes After COVID-19 Infection Using Artificial Intelligence-Based MRI Volumetry

<b>Background/Objectives</b>: SARS-CoV-2 infection has been linked to long-term neurological sequelae and structural brain alterations. Previous analyses, including baseline results from the COVIMMUNE-Clin study, showed brain volume reductions in COVID-19 patients. Longitudinal data on progression are scarce. This study examined brain volume changes 12 months after baseline MRI in individuals who have recovered from mild or severe COVID-19 compared with controls. <b>Methods</b>: In this IRB-approved cohort study, 112 out of 172 recruited age- and sex-matched participants (38 controls, 36 mild/asymptomatic 38 severe COVID-19) underwent standardized brain MRI 12 months after baseline. Volumetric analysis was performed using AI-based software (mdbrain). Regional volumes were compared between groups with respect to absolute and normalized values. Multivariate regression controlled for demographics. <b>Results</b>: After 12 months, a significant decline in right hippocampal volume was observed across all groups, most pronounced in severe COVID-19 (SEV: Δ = -0.32 mL, <i>p</i> = 0.001). Normalized to intracranial volume, the reduction remained significant (SEV: Δ = -0.0003, <i>p</i> = 0.001; ASY: Δ = -0.0001, <i>p</i> = 0.001; CTL: minimal reduction, Δ ≈ 0, <i>p</i> = 0.005). Minor reductions in frontal and parietal lobes (e.g., right frontal SEV: Δ = -1.35 mL, <i>p</i> = 0.001), largely fell within physiological norms. These mild regional changes are consistent with expected ageing-related variability and do not suggest pathological progression. No widespread progressive atrophy was detected. <b>Conclusions</b>: This study demonstrates delayed, severity-dependent right hippocampal atrophy in recovered COVID-19 patients, suggesting long-term vulnerability of this memory-related region. In contrast, no progression of atrophy in other areas was observed. These findings highlight the need for extended post-COVID neurological monitoring, particularly of hippocampal integrity and its cognitive relevance.