With the flurry of COVID-19 cases coming out of the White House, experts have been calling for classic contact tracing to identify who else might be at risk. But these investigations could go even further by adding a technique called viral genome sequencing. Popular among disease detectives, this could answer when and how President Donald Trump himself was exposed.
Much of the focus has been on a September 26 event in the Rose Garden, where the president announced his nomination of Judge Amy Coney Barrett for the vacancy on the Supreme Court. The gathering has been described as a superspreader event, as at least a dozen guests have reported testing positive since. A debate has flared over whether the White House has done enough to trace; guests weren’t immediately notified, and the involvement by the Centers for Disease Control and Prevention has been restricted. Meanwhile, the cluster continues to grow, as a Federal Emergency Management Agency memo reported October 7 that so far, 34 White House staffers, housekeepers, and "other contacts" have been infected with the coronavirus, along with the president, the First Lady, a Navy admiral, and a number of campaign aides.
But Trump and his cadre may have been exposed before the Barrett ceremony, given social distancing and mask wearing aren’t always practiced at their campaign events. Using viral genome sequencing would not only help public health officials sketch the timeline of how the disease spread, but could convey whether the afflicted were exposed at various moments and places on the campaign trail, or all at once.
Here’s how that would work. The virus that causes COVID-19 has a genome based on RNA, which like DNA, is made up of a sequence of chemical “letters” called nucleotides. As the coronavirus invades people’s cells and multiplies, it naturally makes mistakes when replicating its genetic code, swapping a few of those letters. “Imagine having to copy 30,000 letters by hand,” says Stephanie Spielman, assistant professor of biological sciences at Rowan University. ”You might make a mistake, and that’s what a mutation is.”
Once a mutation occurs, it remains in future copies, creating a lineage called a variant. Just swab a bunch of infected noses, compare the variants, and you can trace the origins.
“If you have clusters of people with similar sequences, that’s a strong indication they had a common source,” says Joshua Michaud, associate director for Global Health Policy at the Kaiser Family Foundation. This procedure could even narrow down where in the country Trump’s contingent caught the coronavirus. (National Geographic contacted the White House for comment but received no reply.)
For both contact tracing and genome sequencing, timing is very important. Rapidly finding people who could potentially expose others to infection is critical to stopping chains of transmission. A recent Lancet paper found that reducing delays in contact tracing after a positive test could prevent as many as 80 percent of new infections. That’s why 10 local health departments in the capital region—including the District of Columbia’s—took the unusual step of issuing an open letter imploring all White House staff and Rose Garden attendees to seek medical advice and take a COVID-19 test.
With viral sequencing, “specimens need to be collected while people are still actively infected,” Michaud explains. But it’s not too late yet to try to uncover what went wrong at the White House.
Tracking a virus through its genes
The White House cluster could keep growing—like an ever-expanding spiderweb—because the coronavirus so easily spreads, and because nine of 10 Americans remain susceptible. Given that the Rose Garden event involved more than 150 people, many of whom are involved with the extensive social demands of a presidential campaign, experts say thousands may have already been exposed after the guests returned home to at least 20 states.
But at the center of the web is the first person who was sick, known as the index case. While math models predict that one person infected with the coronavirus typically spreads it to an average of two to three others, field studies show 10 to 20 percent of cases might be responsible for as much as 80 to 90 percent of all coronavirus transmission. In other words, superspreaders—cases that transmit to more than three people—are normal.
Viral sequencing has been used to decipher superspreader incidents in other parts of the world with great success. In New Zealand, for example, two recent clusters were investigated using genomic sequencing, along with contact tracing and interviews, eventually zeroing in on a trash can lid and an elevator button as the likeliest sources of transmission. Another example comes from Germany, where one sick person in a meat processing facility was found to have infected more than 60 percent of his co-workers over distances of more than 26 feet.
The technique is particularly useful in outbreaks where there may be multiple sources of transmission, such as at workplaces, on flights, or in nursing homes. In one CDC study of an Australian commercial flight, for example, nine passengers had recently departed a cruise ship that had a coronavirus outbreak. Two days after the flight, 11 other passengers developed symptoms and tested positive for COVID-19. Genomic sequencing showed that the virus variant was the same on the cruise and on the flight—and was a variant completely new to Australia.
Studies also show that when used with classic contact tracing, genomic sequencing can make interventions more precise, helping reduce transmission. Take a study of six care homes in London, where 40 percent of residents had been infected. Genetic sequencers identified that asymptomatic residents and staff were acting as potential reservoirs, information that led to increased testing, even in people who didn’t appear sick.
Genetics could also clarify how the virus is moving around the country—and could pinpoint where the president was exposed. Emma Hodcroft, a molecular epidemiologist at the University of Basel in Switzerland, says some coronavirus variants can be pinned to specific states, or even counties. “For example, there are distinct clusters in Wisconsin, as well as Washington and Texas.” With the president’s travel history or contacts list, genomic sequencing could potentially link his virus to a certain location. In general, more widespread use of sequencing could tell local authorities who is spreading the virus “between states, between cities, or in cities,” she adds.
For example, analysis of 84 SARS-CoV-2 genomes across Arizona revealed that the virus was introduced into the state at least 11 times during February and March. But none of these COVID-19 clusters were linked to the state’s first known travel-related case, suggesting that early isolation and quarantine of that case successfully contained transmission. The study also found that 80 percent of the sequences descended from European variants, suggesting the travel ban on China did nothing to stop the early spread of the disease in Arizona.
If White House officials decide to use genetic sequencing, as experts have called for, they could better determine how to stop the virus from spreading among the country’s political leaders.
In the case of the 12 positive cases from the Rose Garden event, a genomics survey could determine how to conduct contact tracing. If they all have the same viral variant, they were likely first exposed there, and you’d want to trace all their contacts since that date. But if they have multiple variants, that could imply more than one person carried COVID-19 into the White House—and then far more people would need to be traced.
If you can’t trace, isolate
Open questions revolve around how often the president himself was being tested before catching the coronavirus, or when his last negative test was. But Marm Kilpatrick, an infectious disease researcher at the University of California, Santa Cruz, says the important thing for people to learn from this situation is that you can’t just assume you’re fine after a negative result.
This lesson is illustrated by how the coronavirus bypassed health surveillance for one of the most secure buildings in the United States—and why potential contacts of the Rose Garden outbreak need to isolate for up to 14 days whether they test positive or not.
The White House was relying on rapid tests from Abbott Laboratories, which were given emergency clearance from the U.S. Food and Drug Administration for use on people who have exhibited symptoms for up to seven days. But the administration used them to screen everyone—including guests who were not presenting any signs of COVID-19.
The problem is that in the first few days, the virus replicates exponentially within the body, says Kilpatrick. Even if the White House had used more sensitive PCR tests—which directly measure genetic material—they still could have missed people with low levels of the virus. On top of that, it’s unclear how the amount of coronavirus in a person, known as the viral load, varies from early in infection to the contagious phase to recovery. And the likelihood of testing positive also depends on whether samples are taken from the nose or throat, and the random collection of cells a swab happens to pick up.
“It should be obvious to everyone after this week that relying on testing alone to prevent transmission is unreliable,” Michaud says. “Other measures are needed, like masking, social distancing, and quarantines.”
To make things harder, the CDC estimates that 50 percent of coronavirus spread happens before symptoms emerge, and there’s surprisingly little data about how much viral load a person needs to be infectious. It can take two to 14 days for symptoms to begin after infection, but on average the incubation period is about five days. But Kilpatrick and his colleagues recently found that if the incubation period is longer, the infectious period starts earlier relative to symptoms, meaning there are more days where an asymptomatic person could make other people sick.
All together, Kilpatrick says, “we don’t know the probability of a test correctly identifying when people are infectious.” A negative test portrays the moment the swab is taken, but this picture can change in a matter of hours. The point is especially relevant to the President’s ability to safely resume public appearances.
So with the limits of testing and in the absence of contact tracing for the Rose Garden event, Kilpatrick says, it's valuable for White House guests to remember that “a negative test result doesn’t make your risk of transmission zero—and that’s what Trump was relying on.”
All things considered, Kilpatrick says, “People have asked why Trump got infected. A better question is, how did he not get infected sooner?”