Like no other disaster in recent memory, the COVID-19 crisis has brought home the importance of networks and connections. How different entities – countries, cities, firms and individuals – are connected has profoundly affected the spread of the virus and continues to determine both its human and economic costs. The very forces that give rise to and disseminate network benefits are now distributing and amplifying the costs of the virus through hub and spoke systems. This brief explores the crisis in the context of network and regional science.