There’s no good place to stand inside the Pandemic Response Lab’s sequencing facility in Queens, N.Y. Take a wrong step, and you’re blocking a gowned-up lab tech as she ferries a plate with the RNA from 384 Covid-19 test samples to a machine that runs a polymerase chain reaction (PCR) test, identifies positives, and extracts them with a robotic arm. A data scientist hurries by, bringing more RNA samples to a device that will convert them into DNA. In the corner are genomic sequencing machines that piece together chopped-up bits of that DNA to identify what form of SARS-CoV-2 a patient has. Name a mutation you’ve heard of, and this lab has seen it, as it takes part in the national and global efforts to sequence virus genomes, spot new and dangerous variations, and stem their spread.
Things are moving in this world with mind-bending speed. Earlier this year, the main concern was alpha, a variant originally identified in the U.K., which seemed to spread more easily than the original “wild type” coronavirus. Toward the end of April, the Pandemic Response Lab (PRL) spotted the delta mutation, first identified in India and believed to be even more contagious than alpha. A variant like alpha or delta is distinguished by changes to its genetic code that have effectively altered the virus’s behavior. Delta has more than 20 differences in its genetic makeup, some of which may make it easier for the spike protein to bind to human cells and help the virus evade antibodies. Sequencing has shown that delta cases make up almost 70% of Covid positives in New York City. The CDC estimates the variant is responsible for 83% of cases nationwide.
In late June, PRL (pronounced “pearl”) started gearing up to screen samples for “delta-plus,” a mixture of mutations first identified in India and South Africa. “On a weekly basis these variant definitions can change,” says Henry Lee, director of genomics at PRL. When they do, software must be updated, samples must be reanalyzed, and authorities must figure out how to respond. It’s like watching a Covid wildfire: Find a new mutation, watch it spread, calibrate a response, find a newer mutation, and watch the process repeat, hoping the response will be more effective this time out.
Lee’s lab sends its sequencing data to New York City’s health department, then epidemiologists use it to study questions such as whether a case is a reinfection or whether it happened in a vaccinated person. In this manner, they assess how dangerous a mutation is—how fast it might spread, how severe it might be, how effective vaccines are against it. Then public- health officials can decide whether to enact safety measures such as masking and quarantining. Sequencing data can also contribute to the long-term fight to end the pandemic by helping pharmaceutical companies plan booster shots.
And yet for all of the value genomic sequencing provides, no one paid the Pandemic Response Lab to start doing it. PRL was formed as a Covid testing site with city funding last fall, then months went by as Lee and his colleagues waited for guidance on how positive samples would be sequenced. Jon Brennan-Badal, the 35-year-old chief executive officer of the company that set up PRL, Opentrons Labworks Inc., remembers being on a call with city officials, trying to work out how to get samples to another lab for this purpose. “The conversation bottomed out, because we were like, ‘Oh, it’s going to take a lot of money to make this happen,’ ” he recalls. Insurers wouldn’t reimburse for it, because sequencing rarely, if ever, influences the treatment of a given case. PRL decided to begin doing the work for free. “It’s a nonrational business decision if you just care about shareholder value,” Brennan-Badal says.
Opentrons had the luxury of being privately held and of having available capital and equipment. Its primary business is supplying the kinds of robotics in use at PRL and other medical facilities, which have been busy throughout the pandemic. Soon the lab will expand its operation to other cities. In March, Opentrons announced the launch of four national Covid testing hubs—in Los Angeles, New York, Seattle, and Washington, D.C.—to help get children back into the classroom. The company will charge $25 for a pooled test; those samples will be shipped back to the Queen's lab for sequencing, with that part, again, on PRL’s dime. “The approach that I took with this is no one is willing to pay for it, but everyone is happy to have it,” BrennanBadal says. “If you asked them, ‘Hey, would you pay an extra dollar for it?’ they’d be like, ‘Whoa, whoa, whoa.’ ”
Scientists and public-health officials across the country would love to see the kind of information Opentrons is producing gathered en masse and fed into a rapid, comprehensive national surveillance system. For much of the pandemic, though, sequencing has been piecemeal, spread between state health departments, academic labs, hospitals, nonprofits, and commercial unicorns such as PRL. The system is so scattered, it’s generous to even call it a system. Different types of labs have different priorities for the data. Some work quickly, some take longer. Some have struggled to obtain samples. Fuzzy regulations have caused delays and headaches all over.
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