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When children are exposed to serious life adversities, Ed Zigler believed that developmental scientists must expediently strive to illuminate the most critical directions for beneficial interventions. In this paper, we present a new study on risk and resilience on adolescents during COVID-19, bookended – in introductory and concluding discussions – by descriptions of programmatic work anchored in lessons learned from Zigler. The new study was conducted during the first two months of the pandemic, using a mixed-methods approach with a sample of over 2,000 students across five high schools. Overall, rates of clinically significant symptoms were generally lower as compared to norms documented in 2019. Multivariate regressions showed that the most robust, unique associations with teens' distress were with feelings of stress around parents and support received from them. Open ended responses to three questions highlighted concerns about schoolwork and college, but equally, emphasized worries about families' well-being, and positive outreach from school adults. The findings have recurred across subsequent school assessments, and strongly resonate with contemporary perspectives on resilience in science and policy. If serious distress is to be averted among youth under high stress, interventions must attend not just to the children's mental health but that of salient caregiving adults at home and school. The article concludes with some specific recommendations for community-based initiatives to address mental health through continued uncertainties of the pandemic. [ABSTRACT FROM AUTHOR]