BackgroundCOVID-19 caused the largest pandemic of the twenty-first century forcing the adoption of containment policies all over the world. Many studies on COVID-19 health determinants have been conducted, mainly using multivariate methods and geographic information systems (GIS), but few attempted to demonstrate how knowing social, economic, mobility, behavioural, and other spatial determinants and their effects can help to contain the disease. For example, in mainland Portugal, non-pharmacological interventions (NPI) were primarily dependent on epidemiological indicators and ignored the spatial variation of susceptibility to infection.MethodsWe present a data-driven GIS-multicriteria analysis to derive a spatial-based susceptibility index to COVID-19 infection in Portugal. The cumulative incidence over 14 days was used in a stepwise multiple linear regression as the target variable along potential determinants at the municipal scale. To infer the existence of thresholds in the relationships between determinants and incidence the most relevant factors were examined using a bivariate Bayesian change point analysis. The susceptibility index was mapped based on these thresholds using a weighted linear combination.ResultsRegression results support that COVID-19 spread in mainland Portugal had strong associations with factors related to socio-territorial specificities, namely sociodemographic, economic and mobility. Change point analysis revealed evidence of nonlinearity, and the susceptibility classes reflect spatial dependency. The spatial index of susceptibility to infection explains with accuracy previous and posterior infections. Assessing the NPI levels in relation to the susceptibility map points towards a disagreement between the severity of restrictions and the actual propensity for transmission, highlighting the need for more tailored interventions.ConclusionsThis article argues that NPI to contain COVID-19 spread should consider the spatial variation of the susceptibility to infection. The findings highlight the importance of customising interventions to specific geographical contexts due to the uneven distribution of COVID-19 infection determinants. The methodology has the potential for replication at other geographical scales and regions to better understand the role of health determinants in explaining spatiotemporal patterns of diseases and promoting evidence-based public health policies.