Olfactory Loss and Brain Connectivity after COVID-19: Structural Follow-Up at One Year.

The structural connectivity from the primary olfactory cortex to the main secondary olfactory areas was previously reported as relatively increased in the medial orbitofrontal cortex in a cohort of 27 recently SARS-CoV-2-infected (COV+) subjects, of which 23/27 had clinically confirmed olfactory loss, compared to 18 control (COV-) normosmic subjects, who were not previously infected. To complement this finding, here we report the outcome of an identical high angular resolution diffusion MRI analysis on follow-up data sets collected in 18/27 COV+ subjects (10 males, mean age ± SD: 38.7 ± 8.1 years) and 10/18 COV- subjects (5 males, mean age ± SD: 33.1 ± 3.6 years) from the previous samples who repeated both the olfactory functional assessment and the MRI examination after ~1 year. By comparing the newly derived subgroups, we observed that the increase in the structural connectivity index of the medial orbitofrontal cortex was not significant at follow-up, despite 10/18 COV+ subjects were still found hyposmic after ~1 year from SARS-CoV-2 infection. We concluded that the relative hyperconnectivity of the olfactory cortex to the medial orbitofrontal cortex could be, at least in some cases, an acute or reversible phenomenon linked to the recent SARS-CoV-2 infection with associated olfactory loss.

Olfactory loss and brain connectivity after COVID-19.

To address the impact of COVID-19 olfactory loss on the brain, we analyzed the neural connectivity of the central olfactory system in recently SARS-CoV-2 infected subjects with persisting olfactory impairment (hyposmia). Twenty-seven previously SARS-CoV-2 infected subjects (10 males, mean age ± SD 40.0 ± 7.6 years) with clinically confirmed COVID-19 related hyposmia, and eighteen healthy, never SARS-CoV-2 infected, normosmic subjects (6 males, mean age ± SD 36.0 ± 7.1 years), were recruited in a 3 Tesla MRI study including high angular resolution diffusion and resting-state functional MRI acquisitions. Specialized metrics of structural and functional connectivity were derived from a standard parcellation of olfactory brain areas and a previously validated graph-theoretic model of the human olfactory functional network. These metrics were compared between groups and correlated to a clinical index of olfactory impairment. On the scanning day, all subjects were virus-free and cognitively unimpaired. Compared to control, both structural and functional connectivity metrics were found significantly increased in previously SARS-CoV-2 infected subjects. Greater residual olfactory impairment was associated with more segregated processing within regions more functionally connected to the anterior piriform cortex. An increased neural connectivity within the olfactory cortex was associated with a recent SARS-CoV-2 infection when the olfactory loss was a residual COVID-19 symptom. The functional connectivity of the anterior piriform cortex, the largest cortical recipient of afferent fibers from the olfactory bulb, accounted for the inter-individual variability in the sensory impairment. Albeit preliminary, these findings could feature a characteristic brain connectivity response in the presence of COVID-19 related residual hyposmia.