Association of COVID-19 related anosmia and the structural development of the primary olfactory cortex and hippocampus among pediatric individuals

Introduction/Objectives: COVID-19 pandemic had a profound impact on the social aspect of child development. However, few studies have examined its impact on the structural development of children's brains—particularly the olfactory bulb—given the reported anosmia often among those who acquired the virus. This study aims to assess potential structural differences in the olfactory system among children with reported past COVID-19 infections compared with children who did not report having COVID-19 using data from the Adolescent Brain and Cognitive Development (ABCD) Study.

Methods: We conducted a time-series analysis of magnetic resonance imaging (MRI) data from the Adolescent Brain and Cognitive Development (ABCD) study to determine if the volume of brain structures associated with the olfactory senses were impacted by COVID-19 infection. The ABCD study is a large-scale, longitudinal open-data neuroimaging study that consists of approximately 12,000 children born between 2006 and 2008 at 21 sites across the United States. We used regression analysis to compare the differences in brain volume growth in the structures of the primary and secondary olfactory cortices from scans taken in 2018-2019 to those from 2021-2022 among children in the COVID-19 substudy. Secondarily we compared brain structure development among those with COVID-19 by whether or not they experienced COVID-related anosmia.

Results: Of the 9,611 children in the sample, 694 reported having COVID-19. We found no significant differences in the brain structures under study. However, among participants with a prior COVID-19 infection, we did find significant differences in the volume of the hippocampus among those who had lost their sense of smell compared to those who had not (-52.68mm³, SE: 26.73; t = -1.97, P = .049).

Conclusions: We found a significant association between children with COVID-related anosmia and smaller hippocampal volume, which may have long-lasting implications for odor discrimination, emotional and memory processing, and potential risks for specific medical conditions. Increased awareness of these complications could help healthcare providers initiate preventative care strategies to mitigate potential adverse outcomes.