The ongoing COVID-19 crisis has put the relationship between spatial structure and disease exposure into relief. Here, we propose that mega regions - clusters of metropolitan regions like the Acela Corridor in the United States are more exposed to diseases earlier in pandemics. We review standard accounts for the benefits and costs of locating in such regions before arguing that pandemic risk is higher there on average. We test this mega region exposure theory with a study of the US urban system. Our results indicate that American mega regions have born the early brunt of the disease, and that three mega regions are hotspots. From this standpoint, the extent more than the intensity of New York's urbanization may be implicated in its COVID-19 experience. We conclude that early pandemic risk is a hitherto unrecognised diseconomy operating in mega regions.