Don't be so sensitive!

Rapid testing for COVID-19 holds a great deal of promise. But will it be sensitive enough in detecting the virus? NCSE Executive Director Ann Reid provides some answers.

test strips

Photo by Marco Verch, (CC BY 2.0)

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How much evidence is needed? That’s a question that scientists have to answer over and over again, no matter what question they’re asking. There’s always a balance to be sought, between detail and precision on the one hand and time and money on the other. The same is true in medicine – is a quick check-up enough, or do the symptoms call for an MRI, biopsy, or overnight monitoring in the hospital? In making every decision, doctors have to weigh the risk of missing an important diagnostic clue against the risk of overtreating, generating a false positive result, or simply overtaxing the medical system.

Such a balancing act is at the heart of current deliberations over the approval of inexpensive, rapid, screening tests into our arsenal of weapons against the coronavirus.

The idea, in a nutshell, is to mass-produce very simple coronavirus tests, much like the familiar home pregnancy tests (except using saliva, not urine), that could be administered at home, as often as daily, with no special equipment. This would help to eliminate the current testing bottlenecks. The trade-off is that these tests would be considerably less sensitive than the clinical tests currently in use. (Remember, sensitivity is the ability to identify true positives, here people who are infected with the virus.) Experts who are advocating for this approach argue that such tests would be sensitive enough to identify people who are shedding a lot of virus and therefore more likely to infect others.

On the face of it, this approach could be absolutely transformative. But there is one big question outstanding: exactly how much less sensitive could these rapid tests be while still being able to detect viral levels that pose a risk to others?

In researching whether this plan would work, I read a lot of papers, talked to an expert, and listened to several interviews with more experts. The most thorough explanation of the idea can be heard on This Week in Virology (a nerdtastic podcast that has been around for years but has become a go-to source of reliable information during the pandemic). But if you want a condensed and extremely clear summary of the idea, the best video I found was this one, from the series MedCram. The full 17 minutes is well worth watching, but the graph below captures the main points.

coronavirus graph

There’s a lot going on here, so let me just highlight the main points. Don’t worry about the units of measure; just know that the y axis reflects levels of virus and the x axis is time, in days. The yellow curve is an estimated time course of a coronavirus infection. When you’re first infected (the beginning of the yellow curve), the amount of virus is very low and going up slowly. After a few days, the virus starts replicating rapidly and the amount of virus climbs rapidly for several days. Once the virus reaches its peak, it declines, but not as quickly as it rose. Some small amount of virus may be detectable for a long time – even weeks in some cases. That’s the long tail on the yellow curve.

Now look at the green horizontal line. That reflects the amount of virus that can be detected by the sensitive clinical tests now in use. These tests are supersensitive – they can detect an infection just a day or two after it begins. And they continue to detect the virus long after the peak levels have declined. It’s worth noting that these tests don’t detect the virus itself, they detect its genetic material. So even if there’s no infectious virus left, genetic fragments from the virus may hang around for weeks and be detected by these tests.

Finally, now take a look at the orange horizontal line. This is the amount of virus that the proposed quick, cheap tests would detect. As you can see, there are times during the infection when the clinical test would detect, and the quick test would fail to detect, the virus. In particular, the quick test would miss the very early stages of infection and the long tail of low virus levels after the infection.

Is this a problem? Advocates for the rapid testing approach argue that the levels of virus being shed very early and very late in the infectious process are not high enough to pose a great risk of spread. Therefore, a negative quick test would mean that the individual should be able to go to school or work without infecting others. If the test could be done every day, it might give a negative result on the first day of infection, but because the amount of virus climbs so rapidly early in the infection, the second day of infection would return a positive result and the person would know not to go to work or school.

It’s all pretty convincing, but to work, four things have to be true. First, it must be possible to develop a cheap, easy test that is sensitive enough to detect virus when there is enough of it to trigger a chain of infection. There are several promising candidates, but they face regulatory hurdles because they are not as sensitive as the gold standard clinical tests. Those regulations will have to be adjusted. Second, it must be possible to produce and distribute millions of tests at an easily affordable cost, say, a dollar a day. Government funding will probably be necessary. The Rockefeller Foundation has invested in the idea, but cannot single-handedly bankroll a program on a national scale. Third, the experts must be right that individuals with low levels of virus, either very early in an infection or after the worst of it has passed, are, indeed, unlikely to transmit the virus to others. Finally, everyone will have to be willing to comply with this regime: if you test positive with the rapid test, you have to stay home – even if you feel fine. If your children test positive, you can’t send them to school. Ideally, positive quick tests will be followed up with clinical-grade tests and contact tracing to track down anyone who might have come into contact with the infected person.

So – is rapid testing a magic bullet? Not quite. But is it an amazingly promising development? Definitely. Stay tuned.

NCSE Executive Director Ann Reid
Short Bio

Ann Reid is a former Executive Director of NCSE.