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New research has poured cold water on the theory that the Covid-19 outbreak in Washington state — the country’s first — was triggered by the very first confirmed case of the infection in the country. Instead, it suggests the person who ignited the first chain of sustained transmission in the United States probably returned to the country in mid-February, a month later.

The work adds to evidence that the United States missed opportunities to stop the SARS-CoV-2 virus from taking root in this country — and that those opportunities persisted for longer than has been recognized up until now.

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“Our finding that the virus associated with the first known transmission network in the U.S. did not enter the country until mid-February is sobering, since it demonstrates that the window of opportunity to block sustained transmission of the virus stretched all the way until that point,” the authors wrote in the paper. The paper has been posted to a preprint server, meaning it has not yet been peer-reviewed or published in a journal.

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The research was led by Michael Worobey, a professor of evolutionary biology at the University of Arizona.

Using available genetic sequence data, Worobey and his co-authors modeled how SARS-CoV-2 viruses would have evolved if the original case, known in the medical literature as WA1 (short for Washington state patient 1), had been the source of the state’s outbreak. They ran the model 1,000 times, comparing the genetic sequences of 300 randomly selected simulated cases to those retrieved from 300 actual patients. The results didn’t jibe.

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“In all likelihood this didn’t start with WA1,” Worobey told STAT in an interview. “It started with some unidentified person who arrived in Washington state at some later point. And we don’t know from where.”

Worobey said the sequence data suggest the infection may have been brought to the country by someone returning from China, or from a nearby Asian country, or even from Asia via British Columbia, Canada.

Trevor Bedford, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle, drew the initial line between the first Washington state case — a man who returned to the state from Wuhan on Jan. 15 — and the state’s first reported case in someone who had not traveled outside the country. That person, a high school student who had been tested negative for influenza, was recognized as a Covid-19 case at the end of February.

Analysis of the genetic sequences of the viruses that infected these two people looked close enough that Bedford concluded SARS-CoV-2 had been spreading undetected in the Seattle area for about six weeks.

But in a series of tweets he posted on Sunday, Bedford said he now concludes that theory was not correct.

“Based on data that’s emerged in the intervening months, I no longer believe that a direct WA1 introduction is a likely hypothesis for the origin of the Washington State outbreak,” he tweeted.

Others agree.

“I’m convinced by the Worobey study,” Kristian Andersen of Scripps Research, an expert on viral genomes, told STAT.

Samuel Scarpino, an assistant professor at Northeastern University’s Network Science Institute, said Worobey’s paper “confirms what a lot of what we were starting to suspect from the epidemiological data, that there were some early introductions in the West Coast that did not spark sustained transmission.”

Worobey and his co-authors estimated that the infection that started the Seattle area outbreak arrived in the country around Feb. 13, shortly after President Trump’s ban on travel from China went into effect on Feb. 2. Thousands of Americans in the country fled back to the United States in the days after the ban was announced.

Worobey said the work isn’t merely an effort to set the historical record straight. If WA1 sparked the Seattle outbreak, there was really little more that could have been done to prevent it. The patient had recognized he was probably ill and alerted his physician to the risk. Public health authorities mapped his travel and contacted his contacts, isolating him and quarantining the people he’d been in contact with.

When the first case of local transmission was linked back to WA1, it appeared that the efforts to contain his infection hadn’t been adequate. But in fact, they probably were, Worobey said.

“Conclusions that the Seattle area was already six weeks into an epidemic by the end of February, rather than two or three, and the notion that stringent efforts to prevent spread had failed in the WA1 case, may have influenced decision-making about how to respond to the outbreak, including whether such measures were worth the effort,” he and his co-authors wrote.

Scarpino said the research supports the idea that contact tracing and isolation can work. “Everything is sort of lining up in the direction that if we’re serious about it, we can control this thing,” he said. “We’re just not being serious about it.”

Worobey’s group also disputed a claim, published earlier this month, that a more transmissible lineage of SARS-CoV-2 viruses has emerged, arguing the increased geographic spread of viruses with that mutation pattern has more to do with timing than with increased infectiousness.

Viruses with these mutations spread from Hubei province to Italy and from there to New York City and began to spread locally undetected for a time. “This viral lineage appears to have been amplified because of luck, not high fitness,” they wrote.

Correction: The headline on an earlier version of this story misstated a key finding of the new research — that the coronavirus took off in the U.S. later than previously thought.

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