Team maps how the coronavirus went global

"When you do early intervention and detection well, it can have a massive impact, both on preventing pandemics and controlling them once they progress," says Michael Worobey. (Credit: Duncan c/Flickr)

Early intervention stamped out coronavirus infections, but subsequent poorly monitored travel allowed the virus to ignite major outbreaks in North America and Europe, new research shows.

The study combines evolutionary genomics from coronavirus samples with computer-simulated epidemics and detailed travel records to reconstruct the spread of coronavirus across the world in unprecedented detail.

Published in the journal Science, the results suggest an extended period of missed opportunity when intensive testing and contact tracing might have prevented SARS-CoV-2 from becoming established in North America and Europe.

The paper also challenges suggestions that link the earliest known cases of COVID-19 on each continent in January to outbreaks detected weeks later, and provides valuable insights that could inform public health response and help with anticipating and preventing future outbreaks of COVID-19 and other zoonotic diseases.

“Our aspiration was to develop and apply powerful new technology to conduct a definitive analysis of how the pandemic unfolded in space and time, across the globe,” says Michael Worobey, a researcher at the University of Arizona. “Before, there were lots of possibilities floating around in a mishmash of science, social media, and an unprecedented number of preprint publications still awaiting peer review.”

A map shows the spread of coronavirus around the world
This schematic map shows early and apparently “dead-end” introductions of SARS-CoV-2 to Europe and the US (dashed arrows). Successful dispersals between late January and mid-February are shown with solid arrows: from Hubei Province, China to Northern Italy; from China to Washington state; and later, from Europe (as the Italian outbreak spread more widely) to New York City and from China to California. (Credit: Andrew Rambaut/U. Edinburgh and Jeffrey Joy/U. of British Columbia

Worobey and colleagues based their analysis on results from viral genome sequencing efforts, which began immediately after the virus was identified and quickly grew into a worldwide effort, unprecedented in scale and pace, that has yielded tens of thousands of genome sequences, publicly available in databases.

Contrary to widespread narratives, the first documented arrivals of infected individuals traveling from China to the US and Europe did not snowball into continental outbreaks, the researchers say.

Instead, swift and decisive measures aimed at tracing and containing those initial incursions of the virus were successful and should serve as model responses directing future actions and policies by governments and public health agencies, the study’s authors conclude.

Tracking spread of coronavirus

A Chinese national flying into Seattle from Wuhan, China on January 15 became the first patient in the US shown to have novel coronavirus infection and the first to have a SARS-CoV-2 genome sequenced. Health experts designated the patient “WA1.” It was not until six weeks later that experts detected several additional cases in Washington state.

“And while all that time goes past, everyone is in the dark and wondering, ‘What’s happening?'” says Worobey, head of the ecology and evolutionary biology department and a member of the BIO5 Institute.

“We hope we’re OK, we hope there are no other cases, and then it becomes clear, from a remarkable community viral sampling program in Seattle, that there are more cases in Washington and they are genetically very similar to WA1’s virus.”

Worobey and colleagues tested the prevailing hypothesis suggesting that patient WA1 had established a transmission cluster that went undetected for six weeks. Although the genomes sampled in February and March share similarities with WA1, they are different enough that the idea of WA1 establishing the ensuing outbreak is very unlikely, they determined.

The researchers’ findings indicate that the jump from China to the US likely occurred on or around February 1 instead.

The results also put to rest speculation that the Washington outbreak—the earliest substantial transmission cluster in the US—may have been initiated indirectly by dispersal of the virus from China to British Columbia, Canada, just north of Washington State, and then spread from Canada to the US.

Multiple SARS-CoV-2 genomes published by the British Columbia Center for Disease Control appeared to be ancestral to the viral variants sampled in Washington state, strongly suggesting a Canadian origin of the US epidemic. However, the present study reveals sequencing errors in those genomes, thus ruling out that scenario.

What happened in Europe

Instead, the new study implicates a direct-from-China source of the US outbreak, right around the time the US administration implemented a travel ban for travelers from China in early February. The nationality of the “index case” of the US outbreak cannot be known for certain because tens of thousands of US citizens and visa holders traveled from China to the US even after the ban took effect.

A similar scenario marks the first known introduction of coronavirus into Europe. On January 20, an employee of an automotive supply company in Bavaria, Germany flew in for a business meeting from Shanghai, China unknowingly carrying the virus and ultimately leading to infection of 16 coworkers. In that case, too, an impressive response of rapid testing and isolation prevented the outbreak from spreading any further, the study concludes. Contrary to speculation, this German outbreak was not the source of the outbreak in Northern Italy that eventually spread widely across Europe and eventually to New York City and the rest of the US.

The authors also show that this China-to-Italy-to-US dispersal route ignited transmission clusters on the East Coast slightly later in February than the China-to-US movement of the virus that established the Washington state outbreak. The Washington transmission cluster also predated small clusters of community transmission in February in California, making it the earliest anywhere in North America.

Early containment

The authors say intensive interventions, involving testing, contact tracing, isolation measures, and a high degree of compliance of infected individuals—who reported their symptoms to health authorities and self-isolated in a timely manner—helped Germany and the Seattle area contain those outbreaks in January.

“We believe that those measures resulted in a situation where the first sparks could successfully be stamped out, preventing further spread into the community,” Worobey says. “What this tells us is that the measures taken in those cases are highly effective and should serve as a blueprint for future responses to emerging diseases that have the potential to escalate into worldwide pandemics.”

To reconstruct the pandemic’s unfolding, the scientists ran computer programs that carefully simulated the epidemiology and evolution of the virus—in other words, how SARS-CoV-2 spread and mutated over time.

“This allowed us to rerun the tape of how the epidemic unfolded, over and over again, and then check the scenarios that emerge in the simulations against the patterns we see in reality,” Worobey says.

“In the Washington case, we can ask, ‘What if that patient WA1 who arrived in the US on January 15, really did start that outbreak?’ Well, if he did, and you re-run that epidemic over and over and over and then sample infected patients from that epidemic and evolve the virus in that way, do you get a pattern that looks like what we see in reality? And the answer was no,” he says.

“If you seed that early Italian outbreak with the one in Germany, do you see the pattern that you get in the evolutionary data? And the answer, again, is no,” he says.

“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,” says coauthor Joel Wertheim of the University of California, San Diego. “Molecular epidemiological analyses are incredibly powerful for revealing transmissions patterns of SARS-CoV-2.”

The researchers then combined other methods with the data from the virtual epidemics, yielding exceptionally detailed and quantitative results.

“Fundamental to this work stands our new tool combining detailed travel history information and phylogenetics, which produces a sort of ‘family tree’ of how the different genomes of virus sampled from infected individuals are related to each other,” says coauthor Marc Suchard of the University of California, Los Angeles.

“Our research shows that when you do early intervention and detection well, it can have a massive impact, both on preventing pandemics and controlling them once they progress,” Worobey says. “While the epidemic eventually slipped through, there were early victories that show us the way forward: Comprehensive testing and case identification are powerful weapons.”

The David and Lucile Packard Foundation, the National Institutes of Health, the European Research Council, the Wellcome Trust, and the Canadian Institutes of Health Research Coronavirus Rapid Response Programme funded the study.

Source: University of Arizona