Posted on by Dr. Francis Collins
It was nearly 10 months ago on January 15 that a traveler returned home to the Seattle area after visiting family in Wuhan, China. A few days later, he started feeling poorly and became the first laboratory-confirmed case of coronavirus disease 2019 (COVID-19) in the United States. The rest is history.
However, new evidence published in the journal Science suggests that this first COVID-19 case on the West Coast didn’t snowball into the current epidemic. Instead, while public health officials in Washington state worked tirelessly and ultimately succeeded in containing its sustained transmission, the novel coronavirus slipped in via another individual about two weeks later, around the beginning of February.
COVID-19 is caused by the novel coronavirus SARS-CoV-2. Last winter, researchers sequenced the genetic material from the SARS-CoV-2 that was isolated from the returned Seattle traveler. While contact tracing didn’t identify any spread of this particular virus, dubbed WA1, questions arose when a genetically similar virus known as WA2 turned up in Washington state. Not long after, WA2-like viruses then appeared in California; British Columbia, Canada; and eventually 3,000 miles away in Connecticut. By mid-March, this WA2 cluster accounted for the vast majority—85 percent—of the cases in Washington state.
But was it possible that the WA2 cluster is a direct descendent of WA1? Did WA1 cause an unnoticed chain of transmission over several weeks, making the Seattle the epicenter of the outbreak in North America?
To answer those questions and others from around the globe, Michael Worobey, University of Arizona, Tucson, and his colleagues drew on multiple sources of information. These included data peretaining to viral genomes, airline passenger flow, and disease incidence in China’s Hubei Province and other places that likely would have influenced the probability that infected travelers were moving the virus around the globe. Based on all the evidence, the researchers simulated the outbreak more than 1,000 times on a computer over a two-month period, beginning on January 15 and assuming the epidemic started with WA1. And, not once did any of their simulated outbreaks match up to the actual genome data.
Those findings suggest to the researchers that the idea WA1 is responsible for all that came later is exceedingly unlikely. The evidence and simulations also appear to rule out the notion that the earliest cases in Washington state entered the United States by way of Canada. A deep dive into the data suggests a more likely scenario is that the outbreak was set off by one or more introductions of genetically similar viruses from China to the West Coast. Though we still don’t know exactly where, the Seattle area is the most likely site given the large number of WA2-like viruses sampled there.
Worobey’s team conducted a second analysis of the outbreak in Europe, and those simulations paint a similar picture to the one in the United States. The researchers conclude that the first known case of COVID-19 in Europe, arriving in Germany on January 20, led to a relatively small number of cases before being stamped out by aggressive testing and contact tracing efforts. That small, early outbreak probably didn’t spark the later one in Northern Italy, which eventually spread to the United States.
Their findings also show that the chain of transmission from China to Italy to New York City sparked outbreaks on the East Coast slightly later in February than those that spread from China directly to Washington state. It confirms that the Seattle outbreak was indeed the first, predating others on the East Coast and in California.
The findings in this report are yet another reminder of the value of integrating genome surveillance together with other sources of data when it comes to understanding, tracking, and containing the spread of COVID-19. They also show that swift and decisive public health measures to contain the virus worked when SARS-CoV-2 first entered the United States and Europe, and can now serve as models of containment.
Since the suffering and death from this pandemic continues in the United States, this historical reconstruction from early in 2020 is one more reminder that all of us have the opportunity and the responsibility to try to limit further spread. Wear your mask when you are outside the home; maintain physical distancing; wash your hands frequently; and don’t congregate indoors, where the risks are greatest. These lessons will enable us to better anticipate, prevent, and respond to additional outbreaks of COVID-19 or any other novel viruses that may arise in the future.
 The emergence of SARS-CoV-2 in Europe and North America. Worobey M, Pekar J, Larsen BB, Nelson MI, Hill V, Joy JB, Rambaut A, Suchard MA, Wertheim JO, Lemey P. Science. 2020 Sep 10:eabc8169 [Epub ahead of print]
Coronavirus (COVID-19) (NIH)
Michael Worobey (University of Arizona, Tucson)
NIH Support: National Institute of Allergy and Infectious Diseases; Fogarty International Center; National Library of Medicine
Posted on by Dr. Francis Collins
Contact tracing, a term that’s been in the news lately, is a crucial tool for controlling the spread of SARS-CoV-2, the novel coronavirus that causes COVID-19. It depends on quick, efficient identification of an infected individual, followed by identification of all who’ve recently been in close contact with that person so the contacts can self-quarantine to break the chain of transmission.
Properly carried out, contact tracing can be extremely effective. It can also be extremely challenging when battling a stealth virus like SARS-CoV-2, especially when the virus is spreading rapidly.
But there are some innovative ways to enhance contact tracing. In a new study, published in the journal Nature Medicine, researchers in Australia demonstrate one of them: assembling genomic data about the virus to assist contact tracing efforts. This so-called genomic surveillance builds on the idea that when the virus is passed from person to person over a few months, it can acquire random variations in the sequence of its genetic material. These unique variations serve as distinctive genomic “fingerprints.”
When COVID-19 starts circulating in a community, researchers can fingerprint the genomes of SARS-CoV-2 obtained from newly infected people. This timely information helps to tell whether that particular virus has been spreading locally for a while or has just arrived from another part of the world. It can also show where the viral subtype has been spreading through a community or, best of all, when it has stopped circulating.
The recent study was led by Vitali Sintchenko at the University of Sydney. His team worked in parallel with contact tracers at the Ministry of Health in New South Wales (NSW), Australia’s most populous state, to contain the initial SARS-CoV-2 outbreak from late January through March 2020.
The team performed genomic surveillance, using sequencing data obtained within about five days, to understand local transmission patterns. They also wanted to compare what they learned from genomic surveillance to predictions made by a sophisticated computer model of how the virus might spread amongst Australia’s approximately 24 million citizens.
Of the 1,617 known cases in Sydney over the three-month study period, researchers sequenced viral genomes from 209 (13 percent) of them. By comparing those sequences to others circulating overseas, they found a lot of sequence diversity, indicating that the novel coronavirus had been introduced to Sydney many times from many places all over the world.
They then used the sequencing data to better understand how the virus was spreading through the local community. Their analysis found that the 209 cases under study included 27 distinct genomic fingerprints. Based on the close similarity of their genomic fingerprints, a significant share of the COVID-19 cases appeared to have stemmed from the direct spread of the virus among people in specific places or facilities.
What was most striking was that the genomic evidence helped to provide information that contact tracers otherwise would have lacked. For instance, the genomic data allowed the researchers to identify previously unsuspected links between certain cases of COVID-19. It also helped to confirm other links that were otherwise unclear.
All told, researchers used the genomic evidence to cluster almost 40 percent of COVID-19 cases (81 of 209) for which the community-based data alone couldn’t identify a known contact source for the infection. That included 26 cases in which an individual who’d recently arrived in Australia from overseas spread the infection to others who hadn’t traveled. The genomic information also helped to identify likely sources in the community for another 15 locally acquired cases that weren’t known based on community data.
The researchers compared their genome surveillance data to SARS-CoV-2’s expected spread as modeled in a computer simulation based on travel to and from Australia over the time period in question. Because the study involved just 13 percent of all known COVID-19 cases in Sydney between late January through March, it’s not surprising that the genomic data presents an incomplete picture, detecting only a portion of the possible chains of transmission expected in the simulation model.
Nevertheless, the findings demonstrate the value of genomic data for tracking the virus and pinpointing exactly where in the community it is spreading. This can help to fill in important gaps in the community-based data that contact tracers often use. Even more exciting, by combining traditional contact tracing, genomic surveillance, and mathematical modeling with other emerging tools at our disposal, it may be possible to get a clearer picture of the movement of SARS-CoV-2 and put more targeted public health measures in place to slow and eventually stop its deadly spread.
 Revealing COVID-19 transmission in Australia by SARS-CoV-2 genome sequencing and agent-based modeling. Rockett RJ, Arnott A, Lam C, et al. Nat Med. 2020 July 9. [Published online ahead of print]
Coronavirus (COVID-19) (NIH)
Vitali Sintchenko (University of Sydney, Australia)