This special issue of the International Regional Science Review illuminates the “geography of COVID-19”, examining the spatial patterns, distribution, and interconnectedness of COVID-19 cases. It explores the regional disparities in infection rates, highlighting how socioeconomic factors, mobility, and healthcare accessibility contributed to these inequalities. The issue is divided into three sections, focusing on regional economic dynamics and labor markets, public health responses and vaccination policies, and social and demographic vulnerabilities. Each section comprises research papers presenting insights and analyses on their respective topics, from labor mobility responses to vaccine hesitancy, job insecurity, regional resilience, and more. This issue underscores the importance of regional science in addressing the multifaceted challenges posed by the pandemic and formulating effective, location-specific strategies to mitigate its impacts.