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The uneven development of the Russian territory in the context of the COVID-19 pandemic implies significant spatial disparities in the infection spread, introduction of restrictive measures, and subsequent economic shocks. Cities that are highly dependent on socio-economic interactions inevitably become the main centres of infection. In this regard, the task of maintaining a balance between regional economic development and epidemiological security is of particular importance. A special hierarchical typology of Russian cities has been developed, which allows us to put forward hypotheses about the differentiated impact of the pandemic on cities. It is assumed that patterns of the infection spread and restrictive measures introduction in general follow the hierarchy of urban centres.