Prognostic Value of Serum/Plasma Neurofilament Light Chain for COVID-19 Associated Mortality

Given the continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), early predictors of coronavirus disease 19 (COVID-19) mortality might improve patients outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuro-axonal injury, have been observed in patients with severe COVID-19. We investigated whether NfL provides non-redundant clinical value to previously identified predictors of COVID-19 mortality. We measured serum or plasma NfL concentrations in a blinded fashion in 3 cohorts totaling 338 COVID-19 patients. In cohort 1, we found significantly elevated NfL levels only in critically ill COVID-19 patients compared to healthy controls. Longitudinal cohort 2 data showed that NfL is elevated late in the course of the disease, following two other prognostic markers of COVID-19: decrease in absolute lymphocyte count (ALC) and increase in lactate dehydrogenase (LDH). Significant correlations between LDH and ALC abnormalities and subsequent rise of NfL implicate multi-organ failure as a likely cause of neuronal injury at the later stages of COVID-19. Addition of NfL to age and gender in cohort 1 significantly improved the accuracy of mortality prediction and these improvements were validated in cohorts 2 and 3. In conclusion, although substantial increase in serum/plasma NfL reproducibly enhances COVID-19 mortality prediction, NfL has clinically meaningful prognostic value only close to death, which may be too late to alter medical management. When combined with other prognostic biomarkers, rising longitudinal NfL measurements triggered by LDH and ALC abnormalities would identify patients at risk of COVID-19 associated mortality who might still benefit from escalated care.

Childhood ADHD and Executive Functioning: Unique Predictions of Early Adolescent Depression

Given the increasing prevalence of adolescent depression, identification of its early predictors and elucidation of the mechanisms underlying its individual differences is imperative. Controlling for baseline executive functioning (EF), we tested separate ADHD dimensions (i.e., inattention, hyperactivity-impulsivity) as independent predictors of early adolescent depression, including temporally-ordered causal mediation by academic functioning and social problems, using structural equation modeling. At baseline, participants consisted of 216 children (67% male) ages 6–9 years old with (n = 112) and without (n = 104) ADHD who subsequently completed Wave 2 and 3 follow-ups approximately two and four years later, respectively. Predictors consisted of separate parent and teacher ratings of childhood ADHD and laboratory-based assessments of key EF domains. At Wave 2, parents and teachers completed normed rating scales of youth academic and social functioning; youth completed standardized assessments of academic achievement. At Wave 3, youth self-reported depression. Baseline inattention positively predicted early adolescent depression whereas childhood hyperactivity-impulsivity and EF did not. Neither academic nor social functioning significantly mediated predictions of depression from baseline ADHD and EF. We consider prediction of early adolescent depression from inattention, including directions for future intervention and prevention research.