Covid-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study (preprint)

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdeltasignificantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in volumetricdelta between groups (p=0.041). The reduced ECdelta in the right amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

Impact of COVID-19 related social isolation on behavioral outcomes in young adults. (preprint)

Social isolation strongly affects our emotions and behavior. Worldwide, individuals experienced prolonged periods of isolation during the first wave of the COVID-19 pandemic when authorities imposed restrictions to reduce the spread of the virus. In this study, we investigated the effects of social isolation on emotional and behavioral outcomes in young adults from Lombardy, Italy, a global hotspot of COVID-19. We leverage baseline (pre-social isolation) and follow-up (mid-or post isolation) data collected from young adults enrolled in the ongoing, longitudinal PHIME study. At baseline, 167 participants completed the ASEBA questionnaires (ASR/YSR) by weblink or in person; 65 completed the ASR between 12-18 weeks after the onset of restrictions. Using the sign test and multiple linear regression models, we examined differences in ASR scores between baseline and follow-up adjusting for sex, age, pre-pandemic IQ (Kaufman Brief Intelligence Tests; K-BIT 2), and time with social restrictions (weeks). Further, we examined interactions between sex and time in social isolation. Participants completed the ASR after spending an average of 14 weeks in social isolation (range 12-18 weeks). Thought Problems increased between baseline and follow-up (median difference 1.0; 1st., 3rd quartile: -1.0, 4.0; p=0.049). Among males, a longer time with social isolation ([≥] 14 weeks) was associated with increased rule-breaking behaviors of 2.8 points. These results suggest the social isolation related to COVID-19 adversely impacted mental health. In particular, males seem to externalize their condition. These findings might help future interventions and treatment to minimize the consequences of social isolation experience in young adults.

Vital signs assessed in initial clinical encounters predict COVID-19 mortality in an NYC hospital system (preprint)

Timely and effective clinical decision-making for COVID-19 requires rapid identification of risk factors for disease outcomes. Our objective was to identify characteristics available immediately upon first clinical evaluation related COVID-19 mortality. We conducted a retrospective study of 8770 laboratory-confirmed cases of SARS-CoV-2 from a network of 53 facilities in New-York City. We analysed 3 classes of variables; demographic, clinical, and comorbid factors, in a two-tiered analysis that included traditional regression strategies and machine learning. COVID-19 mortality was 12.7%. Logistic regression identified older age (OR, 1.69 [95%CI, 1.66-1.92]), male sex (OR, 1.57 [95%CI, 1.30-1.90]), higher BMI (OR, 1.03 [95%CI, 1.102-1.05]), higher heart rate (OR, 1.01 [95%CI, 1.00-1.01]), higher respiratory rate (OR, 1.05 [95%CI, 1.03-1.07]), lower oxygen saturation (OR, 0.94 [95%CI, 0.93-0.96]), and chronic kidney disease (OR, 1.53 [95%CI, 1.20-1.95]) were associated with COVID-19 mortality. Using gradient-boosting machine learning, these factors predicted COVID-19 related mortality (AUC=0.86) following cross-validation in a training set. Immediate, objective and culturally generalizable measures accessible upon clinical presentation are effective predictors of COVID-19 outcome. These findings may inform rapid response strategies to optimize health care delivery in parts of the world who have not yet confronted this epidemic, as well as in those forecasting a possible second outbreak.