BackgroundThe COVID-19 pandemic has led to widespread public health measures to reduce transmission, morbidity, and mortality attributed to the SARS-CoV-2 virus. While much research and focus surrounds COVID-19 vaccine development, testing, and supportive management, little is known about the determinants of non-medical, personal impact of COVID-19 prevention policies. We aimed to understand determinants of non-medical COVID-19 impact and to account for its multileveled, intersectional nature of associations.MethodsThis cross-sectional, multi-level, convergent mixed-methods study assessed a range of beliefs, practices, and experiences relating to COVID-19. We recruited a global sample (n=7,411) using both Facebook and Amazon mTURK platforms. We constructed a novel data-driven non-medical COVID-19 Impact Score and four subcomponents (“Personal Action,” “Supply-related,” “Cancellations,” and “Livelihood” impacts). We used generalized estimating equation models with identity link functions to determine concomitant association of individual, household, and country-level variables on the impact scores. We also classified 20,015 qualitative excerpts from 6859 respondents using an 80-code codebook.ResultsTotal and component impact scores varied significantly by region with Asia, Africa, and Latin America and the Caribbean observing the highest impact scores. Multilevel modeling indicated that individual-level sociocultural variables accounted for much of this variation with COVID-related worry, knowledge, struggles in accessing food and supplies, and worsening mental health most strongly associated with non-medical impact. Family responsibilities, personal COVID medical experience, and health locus of control – in addition to country-level variables reflecting social and health challenge – were also significantly and independently associated with non-medical impact.DiscussionNon-medical personal impact of COVID-19 affects most people internationally, largely in response to shutdowns, implementing prevention requirements, and through economic consequences. In the context where most of the world’s population does not have direct medical experience with COVID-19, this phenomena of non-medical impact is profound, and likely impacts sustainability of public health interventions aimed at containing COVID-19.