The transformation that COVID-19 has brought upon the world is unparalleled. The impact on mental health is equally unprecedented and yet unexplored in depth. An online-based survey was administered to 413 community-based adults during COVID-19 confinement to explore psychological impact and identify high risk profiles. Young females concerned about the future, expressing high COVID-related distress, already following psychological therapy and suffering from pre-existing chronic conditions, were those at highest risk of psychological impact due to the COVID-19 situation. Findings could be employed to design tailored psychological interventions in the early stages of the outbreak to avoid the onset/exacerbation of psychopathology.