Abstract Up to now, studies on environmental, climatic, socio-economic factors, and non-pharmacological interventions (NPI) show diverse associations, often contrasting, with COVID-19 spread or severity. Most studies used large-scale, aggregated data, with limited adjustment for individual factors, and most of them focused on viral spread rather than severe outcomes. Moreover, evidence simultaneously evaluating variables belonging to different exposure domains is scarce, and none analysing their collective impact on an individual level. Our population-based retrospective cohort study aimed to assess the comprehensive role played by exposure variables belonging to four different domains, environmental, climatic, socio-economic, and non-pharmacological interventions (NPI), on individual COVID-19-related risk of hospitalization and death, analysing data from all patients (n.68472) tested positive to a SARS-CoV-2 swab in Modena Province (Northern Italy) between February 2020 and August 2021. Using adjusted Cox proportional hazard models, we estimated the risk of severe COVID-19 outcomes, investigating dose-response relationships through restricted cubic spline modelling for hazard ratios. Several significant associations emerged: long-term exposure to air pollutants (NO2, PM10, PM2.5) was linked to hospitalization risk in a complex way and showed an increased risk for death; while humidity was inversely associated; temperature showed a U-shaped risk; wind speed showed a linear association with both outcomes. Precipitation increased hospitalization risk but decreased mortality. Socio-economic and NPI indices showed clear linear associations, respectively negative and positive, with both outcomes. Our findings offer insights for evidence-based policy decisions, improving precision healthcare practices, and safeguarding public health in future pandemics. Refinement of pandemic response plans by healthcare authorities could benefit significantly. Key messages • Evaluating simultaneously four exposure domains on COVID-19 outcomes informs public health policy for future pandemic management. • The comprehension of risk factors associated with severe outcomes, such as hospitalization and mortality, is pivotal for planning responses to similar health emergencies in the future.
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