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Genomic Epidemiology Studies Retrace Sources of Early SARS-CoV-2 Outbreaks in US, Europe

NEW YORK – For weeks, SARS-CoV-2 was circulating under the radar in Washington State. But for how long and from which introduction?

Now, studies by independent research teams are providing a closer look at such cryptic transmission in the US and other parts of the world, as well as the effectiveness of early mitigation attempts.

In the first of two papers published in Science on Thursday, a team from the US and Belgium combined genome sequence data with outbreak simulations, phylogenetic analyses, viral diversity data, airline passenger information, and other epidemiological clues to retrace SARS-CoV-2 sources and spread in North America and Europe.

When it came to sustained coronavirus spread, the researchers identified clusters that lined up with introductions that have been documented in the past. In Washington State, for example, their analyses and simulations on up to 1,000 SARS-CoV-2 genomes hinted that an outbreak in that area stemmed from a second SARS-CoV-2 introduction that was slightly later than the case detected in mid-January that was previously thought to be the source of extensive community spread.

"Our analyses … delineated when widespread community transmission was first established on both continents and clarify the period before SARS-CoV-2 establishment when contract tracing and isolation might have been most effective," the authors wrote.

On the other hand, the team saw signs that the virus arrived in Italy and in Germany from Hubei in late January, rather than moving from Germany to Italy, as suspected. From there, strains from Italy contributed to the multiple European introductions detected in New York City, where a large transmission cluster got its start in NYC in mid-February.

"By re-running the introduction of SARS-CoV-2 into the US and Europe through simulations, we showed that it was very unlikely that the first documented viral introductions into these locales led to productive transmission clusters," co-senior and co-corresponding author Joel Wertheim from the University of California at San Diego's department of medicine said in a statement. "Molecular epidemiological analyses are incredibly powerful for revealing transmissions patterns of SARS-CoV-2."

Still, he and his colleagues uncovered signs of some successful containment in Washington State, Germany, and elsewhere, in advance of additional introductions that spread more widely.

"Despite the early successes in containment, SARS-CoV-2 eventually took hold in both Europe and North America during the first two months of 2020: first in Italy around the end of January, then in Washington State around the beginning of February, followed by New York City later that month," Wertheim and co-authors explained.

The Washington State findings from their analyses complemented those reported in a related Science paper Thursday. That work — from researchers at Fred Hutchinson Cancer Research Center, the Brotman Baty Institute for Precision Medicine, the University of Washington, and elsewhere — focused mainly on more than 450 SARS-CoV-2 genome sequences from Washington State.

The team, which included Nextstrain members, identified a cluster stemming from transmission events that started taking off toward the end of January or early February, slightly after the case that caused concern in mid-January.

More broadly, that study also emphasized the insights that were gained by tapping into sequence data from an ongoing flu surveillance study in Seattle, which helped to identify early COVID-19 cases that would likely have been missed otherwise.

"Our results highlight the critical need for widespread surveillance for community transmission of SARS-CoV-2 throughout the United States and the rest of the world even after the current pandemic is brought under control," the authors wrote, concluding that "[w]e see the combination of community surveillance, genomic analysis, and public real-time sharing of results as empowering new systems for infectious disease surveillance."