SARS-CoV-2 infection is associated with functional changes in resting-state neural mechanisms among Italian adolescents and young adults: a longitudinal case control study

Background: There is strong evidence for brain-related abnormalities COVID-19. Neurologic, cognitive, and olfactory deficits demonstrate the potential neurotoxic impact of the virus. Recent studies of covid-related brain changes focus on severe infection or older populations. To our knowledge, no studies have focused on brain changes in adolescents and young adults impacted mildly by COVID-19. We took a data-driven approach to identify functional brain changes in COVID-19 cases and controls from Lombardy, Italy, a global hotspot of COVID-19. Methods: From our ongoing longitudinal neuroimaging study of adolescents in Northern Italy (the Public Health Impact of Metals Exposure (PHIME) study), we selected 10 participants (age 16-25y) who tested positive for SARS-CoV-2 infection (confirmed via real-time reverse transcription polymerase chain reaction (RT-PCR) tests) and 11 age- and sex-matched non-infected controls (RT-PCR negative; no close-contact or self-reported symptoms). None of the 10 positive subjects were hospitalized or suffered from pneumonia. All participants completed resting state functional magnetic resonance imaging (rs-fMRI) studies prior to and after infection. Using graph theory metrics, we computed eigenvector centrality (EC) in 111 brain areas (Harvard Oxford Atlas) and computed ECdelta (i.e., the difference in EC values pre- and post-COVID-19). We used family wise error (FWE) corrected permutation statistics to quantify ECdelta differences between cases and controls. Results: ECdelta in four brain regions (right posterior temporal gyrus; right planum temporale; left insular cortex and left central opercular cortex; p= 0.034, 0.047, 0.016, 0.038, respectively) differed significantly between COVID-cases and matched controls. Conclusions: To our knowledge, this is the first longitudinal imaging study of COVID-19 in adolescence where participants were scanned before and after SARS-CoV-2 infection. Our results show that key brain areas associated with the primary gustatory cortex (insula and opercular cortex) and the ‘brain-fog’ (temporal gyrus and planum temporale) have altered functional connectivity patterns in adolescents infected by SARS-CoV-2.