Last week’s U.S. approval of the first at-home test for the COVID-19 virus was welcome news, but it also underscored the perverse situation in which we find ourselves. Ten months into the pandemic, and the situation with American testing remains a debacle.
Granted, COVID-19 testing has improved significantly throughout the year. As of last weekend, more than 177 million tests had been performed. But in a country with some of the best clinical laboratories in the world, what went wrong? At a recent annual meeting of the Association for Molecular Pathology, experts talked about what’s being done well — and where things fell apart.
Regulatory hurdles
Clinical labs in this country were remarkably slow to begin testing for the SARS-CoV-2 virus, with the first patient results not being returned until many weeks after the pandemic spilled across our borders. The problem wasn’t test development; indeed, a number of labs developed new assays to detect the virus much earlier. But no clinical laboratory is permitted to issue patient results for a new test without getting proper regulatory approval, and the FDA took weeks to release guidelines on how these tests could be submitted for regulatory clearance.
Most countries got testing up and running quickly using a SARS-CoV-2 test developed in conjunction with the World Health Organization. But in the U.S. the only test to receive regulatory approval came weeks later, from the Centers for Disease Control and Prevention. Labs immediately jumped to implement it, but unfortunately, contamination of some of the early batches of chemicals needed for the test led to flawed results. That set testing in this country back even longer.
Testing behemoth Quest Diagnostics brought its own test online in early March. One of the key challenges it faced — a problem echoed by many lab experts — was getting access to the dozens of positive samples the FDA required they use to ensure a test’s accuracy. With labs around the world trying to validate COVID-19 tests, there was tremendous competition for samples that had already been confirmed as positive. Quest worked with a partner lab in South Korea to secure such samples and prove that its own test accurately detected the virus in them.
Scaling up
We’ve come a long way from those very first FDA-cleared test results. Clinical labs across the U.S. “have done yeoman’s work” racing to scale up testing capacity, said Carlos del Rio, an infectious disease doctor and faculty member at Emory University School of Medicine.
The numbers have been staggering. Quest Diagnostics, for example, increased capacity from 2,000 tests daily in March to 200,000 virus tests every day by July, along with another 200,000 antibody tests daily. Smaller clinical labs have upscaled similarly: at the University of Michigan, clinical pathologist Michael Bachman reported that virology testing in his facility increased 15-fold, so much that other labs have had to pitch in to meet demand.
These capacity surges go far beyond turning the crank on a test machine more often. Due to supply chain limitations for ingredients and equipment, labs that typically validate only one or two tests for any particular condition had to bring in far more testing platforms in order to reduce their reliance on the consumables required by any one test maker. “I’ve seen them put five, six, seven platforms just because there’s not enough tests [available to run] on any one,” del Rio said. That’s a huge strain on clinical laboratory professionals, who have to perform extensive validation protocols before using any new test or system.
While diversifying the test platforms has helped alleviate supply shortages, it has certainly not solved the ongoing problems. “Every day is a day of which hole do I plug?” said Beth Marlowe from Quest Diagnostics.
Misdirected testing
Countries that have decisively beaten back the pandemic have one thing in common: a clear testing strategy with strong links to patient isolation and contact tracing. Ideally, testing would be performed to identify positive cases, followed by immediate isolation of that person and anyone they had been in close contact with the past few days. In the U.S., though, contact tracers are actively stymied in their efforts as many people refuse to cooperate, and test results have not come back quickly enough to make isolation effective.
This is why even ramped-up testing capacity has not given us the upper hand in the fight against COVID-19. “The U.S. right now is consuming about 60% of all the testing capabilities in the world and we still don’t have enough,” del Rio said. “I think contact tracing has really, really failed significantly in our country … and if you don’t have good contact tracing, then testing doesn’t work.”
Another problem with the testing mindset here has been a false sense of security among people who receive negative test results. A negative result can mean the person isn’t infected; it can also mean the person was infected too recently to have enough virus in his or her body to currently test positive, or it can be a false negative. False negatives, said del Rio, are “the biggest concern that I have.”
Even people with negative results need to mask up, wash their hands often, and keep their distance from others. After all, del Rio said, “Using testing regularly to prevent COVID-19 is like using pregnancy testing regularly to prevent pregnancy. It doesn’t work that way.”
Surveillance is key
Especially when testing is misused, surveillance screening to spot positivity trends at the broader population level is important. At Emory, for instance, del Rio noted that 50% to 60% of positive cases among students are people who have no symptoms or only very mild ones.
A different kind of surveillance screening was an early bright spot in the U.S. At the University of Washington, scientists who ran an ongoing community screening study for influenza were able to pivot quickly, applying their sample collection and testing resources to look for signs of the pandemic. While they were not able to use this pipeline to return clinical results, due to foot-dragging from the FDA, they were able to start running samples for research to see whether the virus turned up. What they found in late February was one of the earliest known cases of community transmission in Washington. “It turned out that there was actually quite a big outbreak right in our back yard,” said Lea Starita, a genome scientist at UW. The federal response to this finding? The lab was immediately told to cease and desist because the test was not clinically approved, Starita said.
The uncontrolled, nationwide pandemic threatens to surge well beyond the capacity and personnel resources that clinical labs can muster. If we have any chance of overcoming this virus, it will be because we change how we view testing and become more open to isolation and contact-tracing protocols.
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