COVID-19 infection and longitudinal changes in olfactory-related brain structures in children: analysis of ABCD study...

The COVID-19 pandemic has profoundly impacted the social aspect of child development. However, few studies have examined its impact on the structural development of children's brains-particularly the olfactory system-given the reported anosmia. 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. We conducted a time-series analysis of MRI data from the ABCD study to determine if the volume of brain structures associated with the olfactory system was impacted by COVID-19 infection. The ABCD study is comprised of approximately 12,000 children born from 2006 to 2008 from 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. Secondarily, we compared brain structure development among those with COVID-19 by whether or not they experienced COVID-related anosmia. Of 2423 participants, 8.1% (n = 195) had prior COVID-19, and 22.97% (n = 34) of those reported anosmia. Children with COVID-19 showed smaller amygdala (P = .023), hippocampus (P = .001), parahippocampal gyrus (P = .004), insula (P = .047), and total cortical volumes (P = .016), with larger volumes in the medial orbitofrontal cortex (P = .047). Those reporting anosmia had a smaller hippocampus (P = .013), right anterior segment of the circular sulcus of the insula (P = .002), left posterior cingulate cortex (P < .001), right posterior cingulate cortex (P = .003), right rostral anterior cingulate cortex (P < .001), and total cortical volume (P < .001) compared to those without anosmia.

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 processing, and memory processing. Increased awareness of these complications could help healthcare providers initiate preventive care strategies.

• COVID-19 infection has been associated with structural brain changes in adults, particularly within limbic and olfactory regions. • The structural effects of COVID-19 on the developing brain remain poorly understood due to limited pediatric imaging studies.

• Using data from the large, multi-site ABCD Study, children with prior COVID-19 infection showed significant volumetric alterations in multiple regions, including smaller limbic and insular structures and larger volumes in select subregions. • Findings reveal region-specific volumetric increases and decreases in children with a history of COVID-19, indicating measurable structural brain differences within the developing pediatric population.