Examining Brain Structures and Cognitive Functions in Patients with Recovered COVID-19 Infection: A Multicenter Study Using 7T MRI.

Importance: Emerging evidence suggests that severe acute respiratory syndrome, COVID-19, negatively impacts brain health, with clinical magnetic resonance imaging (MRI) showing a wide range of neurologic manifestations but no consistent pattern. Compared with 3 Tesla (3T) MRI, 7 Tesla (7T) MRI can detect more subtle injuries, including hippocampal subfield volume differences and additional standard biomarkers such as white matter lesions. 7T MRI could help with the interpretation of the various persistent post-acute and distal onset sequelae of COVID-19 infection. Objective: To investigate the differences in white matter hyperintensity (WMH), hippocampal subfields volumes, and cognition between patients hospitalized with COVID-19 and non-hospitalized participants in a multi-site/multi-national cohort. Design: Original investigation of patients hospitalized with COVID-19 between 5/2020 and 10/2022 in 3 USA and 1 UK medical centers with follow-up at hospital discharge. Participants: A total of 179 participants without a history of dementia completed cognitive, mood and other assessments and MRI scans. Exposure: COVID-19 severity, as measured by hospitalization vs no hospitalization. Main Outcomes and Measures: 7T MRI scans were acquired. All WMH and hippocampal subfield volumes were corrected for intracranial volumes to account for subject variability. Cognition was assessed using a comprehensive battery of tests. Pearson correlations and unpaired t-tests were performed to assess correlations and differences between hospitalized and non-hospitalized groups. Results: We found similar WMH volume (4112 vs 3144mm³, p=0.2131), smaller hippocampal volume (11856 vs 12227mm³, p=0.0497) and lower cognitive and memory performance, especially the MoCA score (24.9 vs 26.4 pts, p=0.0084), duration completing trail making test B (97.6 vs 79.4 seconds, p=0.0285), Craft immediate recall (12.6 vs 16.4 pts, p<0.0001), Craft delay recall (12.0 vs 15.6 pts, p=0.0001), and Benson figure copy (15.2 vs 16.1 pts, p=0.0078) in 52 patients hospitalized for COVID-19 (19[37%] female; mean[SD] age, 61.1[7.4] years) compared with 111 age-matched non-hospitalized participants (66[59%] female; mean[SD] age, 61.5[8.4] years). Conclusions and Relevance: Our results indicate that hospitalized COVID-19 cases show lower hippocampal volume when compared to non-hospitalized participants. We also show that WMH and hippocampal volumes correlate with worse cognitive scores in hospitalized patients compared with non-hospitalized participants, potentially indicating recent lesions and atrophy. Key Points: Question: Do white matter hyperintensity burden, hippocampal whole and subfield volumes, and cognition differ between patients hospitalized with COVID-19 versus participants without hospitalization?Findings: We found no significant difference in white matter hyperintensity volume, but hippocampal volume was reduced, and cognitive and memory performance were worse in those hospitalized for COVID-19 compared with age-matched non-hospitalized group (either mild COVID-19 or no COVID-19 reported). In the hospitalized group, increased white matter hyperintensity and reduced hippocampal volumes are significantly higher correlated with worse cognitive and memory scores.Meaning: Adults hospitalized for COVID-19 had lower hippocampal volumes and worse cognitive performance than adults with COVID-19 that did not lead to hospitalization or without reported COVID-19 infection.