Get Ready for a Wave of Missed Infections

At last, rapid COVID tests are everywhere—and that means a surge of false-negative results.

Pattern made up of COVID rapid-test strips
Getty

COVID-19 tests were in such short supply during the winter’s Omicron surge that most infections—affecting up to three out of four Americans by some estimates—went entirely undiagnosed. Now, with abundant rapid tests and another looming wave of cases, we may soon confront a different problem: Large numbers of infections will be missed in the coming months because these tests are so widespread.

America’s COVID-detection program has entered a novel phase. Thanks to the entrance of new over-the-counter diagnostic manufacturers and the federal government’s promise to send up to eight tests to every home, a COVID diagnosis is, at this point, far more likely to be obtained through self-swabbing than through lab-based PCR techniques. One of more than a dozen companies, iHealth, is producing 300 million rapid antigen devices per month, while all the country’s labs put together have maxed out at conducting just 2.5 million tests a day. Because rapid results are rarely reported to public-health agencies, that means our early-warning system may now be somewhat less sensitive than it was before. More important, these tests’ ubiquity could bring a wave of false-negative results in tandem with the next wave of illness—and thus a wave of missed opportunities for treatment.

A sense that rapid tests might not be entirely reliable emerged during the Omicron outbreak, when Americans were just getting used to running their own makeshift personal laboratories. Asking millions of citizens to perform self-tests for the first time in the midst of the winter’s sudden, unprecedented viral tsunami turned out to be unintentionally cruel. Consumers sought out help from social media, where misinformation is rampant. Many people felt confusion and regret when their home devices missed cases, putting their friends and family at risk. The need to explain away these false negatives became almost existential. Experts composed tortuous Twitter threads taking readers through the developing science. People wondered whether rapid tests no longer worked against the Omicron variant. Speculation arose that additional throat sampling was needed on top of standard nasal swabbing, and media outlets gave instructions on how to do so—in open defiance of the FDA.

The dust has now settled, and the answer as to why so many tests came up short is relatively straightforward: Many people received false-negative antigen results because this technology has always been likely to produce false negatives. Rapid tests are known to miss about 30 to 40 percent of infections compared with the gold-standard PCR method (which already isn’t perfect), even when patients are feeling sick; self-swabbing is also less accurate than professionally obtained samples. Meanwhile, multiple studies have confirmed that the current crop of rapid tests can indeed pick up the Omicron variant, and experiments with throat swabbing suggest that the technique might help a bit but isn’t a game changer. In other words, incorrect COVID-test results became more common during the Omicron surge only because COVID home testing itself became more common. Now both will be more common still.

Rapid-test advocates have long emphasized the technology’s public-health potential: Despite the fact that these affordable devices miss many cases overall, they still diagnose the majority of actively infectious people (especially with repeated testing). The widespread screening of asymptomatic people has been encouraged to help keep public gatherings safe and break chains of transmission. Under this testing model, receiving an incorrect result wasn’t crucial, because that individual was unlikely to spread the coronavirus. But things are very different in 2022: The Biden administration is in the midst of rolling out a nationwide test-to-treat program, in which local pharmacies and health centers will provide on-site testing and immediate prescriptions for anyone who turns up positive. Early-treatment options for COVID—antiviral pills such as Paxlovid and Molnupiravir, infusions such as Remdesivir and monoclonal antibodies, and hopefully other options soon—promise to blunt some of the remaining risk from the virus among unvaccinated and high-risk vaccinated people. As these treatments must be started within five to seven days of symptom onset (depending on the therapy), eligibility requires the timely receipt of a positive result—and rapid tests will be essential. So what will happen when, as one Omicron-era study found, antigen tests start missing one in four patients whose symptoms have started in the past week?

Repeated self-testing after a negative result is officially recommended. Still, some users are likely to feel misled after months of advocacy suggesting that rapid tests catch nearly 100 percent of “infectious” cases. The distinction between “infected” and “infectious”—that is, between those who are carrying the virus and those who are carrying enough of it to transmit the infection to others—will be lost on many lay consumers, but the former is all that matters for treatment. Vulnerable individuals who are experiencing COVID-like symptoms may worry less about whether they’re infectious than whether a regimen of Paxlovid would cut their risk of hospitalization or death by 88 percent. With stakes so high, a single negative rapid test won’t provide sufficient clarity.

Even as rapid testing takes precedence, follow-up PCR samples should still be used to exclude the need for treatment. Repeating antigen tests over several days will also help. Health-care providers participating in the test-to-treat program can offer this type of guidance directly, but many people receiving negative diagnoses at home are bound to feel falsely reassured without more explicit scientific coaching. Better education on the use of rapid tests could be ramping up while case rates remain modest.

The increasing availability of home testing is a boon for the public, as is the development of effective outpatient interventions for COVID. Yet the combination of these two advances is likely to produce a false-negative wave—whether in the coming weeks, from the BA.2 sub-variant, or later on, from some other future viral offshoot. If infections once again reach Omicron’s historic peak, then millions of treatable cases could be missed if only a single antigen test is taken each time. The official White House line is that Americans now have “all the tools we need to protect each other and treat COVID-19.” But to save every life that we can, the public must first know how to use these tools properly.