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The pandemic has been particularly devastating to America’s biggest cities, as the virus has found fertile ground in the density that is otherwise prized. And it comes as the country’s major urban centers were already losing their appeal for many Americans, as skyrocketing rents and changes in the labor market have pushed the country’s youngest adults to suburbs and smaller cities often far from the coasts.

The country’s three largest metropolitan areas, New York, Los Angeles and Chicago, all lost population in the past several years, according to an analysis by William Frey, a demographer at the Brookings Institution. Even slightly smaller metro areas, like Houston, Washington, D.C., and Miami grew more slowly than before. In all, growth in the country’s major metropolitan areas fell by nearly half over the course of the past decade, Mr. Frey found.

Now, as local leaders contemplate how to reopen, the future of life in America’s biggest, most dense cities is unclear. Mayors are already warning of precipitous drops in tax revenue from joblessness. Public spaces like parks and buses, the central arteries of urban life, have become danger zones. And with vast numbers of professionals now working remotely, some may reconsider whether they need to live in the middle of a big city after all.

Before the pandemic, millennials and older members of Generation Z were already increasingly choosing smaller metro areas like Tucson, Ariz.; Raleigh, N.C.; and Columbus, Ohio, according to Mr. Frey. Also growing were exurbs and newer suburbs outside large cities.

“There was a dispersion from larger metros to smaller metros, from urban cores to suburbs and exurbs,” he said.

Cities boomed in the 1990s, after two decades of stagnation, lifted by new waves of immigration and vibrant economic growth that attracted newcomers.

But by the mid-2010s, the growth slowed. Big cities had become expensive, with rents far out of the range of the middle-income American. The economy was changing too: Low-wage jobs, after adjusting for the local cost of living, paid about the same everywhere.

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