Expand Rapid Testing to Help Counter COVID Variant Spread, Says Harvard Epidemiologist Michael Mina

I just returned from an enlightening trip to CVS, to photograph Abbott Lab’s at-home rapid antigen test for COVID, BinaxNOW. It became available at three major drugstore chains on April 19.

“Do you have the rapid COVID test? The at-home one?” I asked the woman behind the pharmacy counter.

Deer-in-the-headlights.

Fortunately, the pharmacist behind her overheard. “Not only don’t we have it, but we don’t know when we’ll be getting it.” I wasn’t too surprised; I live in a small town.

So I got on line to buy some vitamin gummies, appropriately socially distanced, and saw to my immediate left a prominent display of items that everyone should have to prevent COVID: wipes, hand sanitizer, gloves, masks. They provided a backdrop to a stack of 6 boxes of – BinaxNOW!

Of course, a detection test to see if you’ve been infected is not at all the same thing as a preventive measure. So I circled back to the pharmacy, and within seconds of notifying the pharmacist that the tests were indeed available, an angry summons for the manager bellowed out over the loudspeaker.

Oops.

It’s a lesson. In the fight against COVID, we must educate ourselves.

Fortunately, many top scientists and physicians have made themselves available throughout the pandemic to educate the media, who then inform the public. I’ve listened in on dozens of these webinars, and written up quite a few.

In a webinar from the Harvard T.H. Chan School of Public Health on April 20, 2021, Michael Mina, MD, PhD, looked back at his comments from a year ago, weighed the current race between vaccines and viral variants, and looked ahead. He’s an assistant professor of epidemiology, a clinical fellow in pathology, and faculty affiliate in immunology and infectious diseases. Here’s my edited version of his talk on variants, testing, and the future.

HOW DOES THE RELATIONSHIP BETWEEN VACCINES AND VARIANTS AFFECT OUR RETURN TOWARDS NORMAL?
We have a very large number of people in the US getting vaccinated, and that has led to a sense of relaxation, especially among the most vulnerable age classes. We need to start getting the community to feel safer, but new variants are continuing to burst onto the scene and keep the country on high alert.

This isn’t surprising, because variants were always on the table. We just weren’t looking for them. The moment we started robust sequencing, we started seeing them. So there’s interplay between vaccines limiting the spread and variant pressure at the community level to increase the spread.

Places are starting to re-open. But what we want as a society directly contradicts control measures. If we want to totally freeze the virus, we don’t move at all. Obviously that’s not sustainable.

WHAT MAKES A VIRAL VARIANT MORE TRANSMISSIBLE AND MORE DANGEROUS?
Not all variants are worrisome. They are a normal part of virus biology.

As viruses replicate, they make errors and small mutations happen. Most create viruses that don’t persist or don’t change the nature of the virus. Every once in awhile, especially when trillions of viruses are growing in people around the world, by chance you’re going to have a virus have a mutation that allows it to grow faster and transmit faster and is more likely to get into more hosts. It outcompetes other viruses and ends up spreading. Even if it doesn’t change the severity of disease, it increases the number of infected individuals, and that creates more hospitalizations and deaths.

We have to keep an eye on 3 pieces: does a virus transmit more, become more destructive to the body, and evade our immune system?

If variants escape immunity it might mean we have to boost people with new vaccines that cover those variants. We don’t want to get to where many different variants each escape the immune system in a different way, so we’re playing catch-up all the time with multiple vaccines.

Some vaccines don’t necessarily work as well for certain variants. One solution is to develop a more universal vaccine that protects against multiple lineages of the virus, maybe by finding a conserved region of the virus to vaccinate against. Another is to include in one vaccine code for multiple proteins.

WHAT DOES ‘MORE TRANSMISSIBLE’ MEAN?
It’s not that the virus does a better job of getting through an N95 mask. Usually it means that the virus levels will stay at peak titers for longer.

Normally viruses grow fast in the body and come down quickly as the immune system tackles them. We have 10 billion viral particles per millimeter in the nose, normally staying at that level for 1 or 2 days. If it stays 3 or 4 days, that might not sound like much longer, but it increases the likelihood that the person will come into contact with someone during that time and spread it.

Or maybe a variant creates more symptoms like a stronger cough, and that spreads it. But we haven’t seen big changes in symptoms.

WHAT WILL THE ROLE OF TESTING BE AS THE PANDEMIC EVOLVES?
Testing is absolutely crucial. With more people vaccinated, that doesn’t mean we can let go of all control measures. We may still need to know if you’re infectious, especially if you walk into a nursing home or assisted living facility. But the testing lens is changing dramatically. The fervor over getting tested has diminished, so people are increasingly unwilling to drive an hour or sit in a parking lot to get a test.

The BinaxNOW at-home rapid test from Abbott (2-in-a-pack for $23.99) became available at drugstores April 19, but the US government has used it over the past year. We’ve created a regulatory pathway for a small number of these tests to come to market over-the-counter. They’re not the public tests I’ve been pushing for to slow community transmission, but it’s one step on the pathway towards that.

I’d like to have seen $1 tests available last summer. That could have helped to prevent the major surges and thousands of deaths last winter. Rapid tests can be produced for 50 cents. Governments can produce and distribute them.

In many countries rapid tests for people to use at home are free, unlike in the US where we charge people to participate in public health. We haven’t gotten around to realizing that testing in a pandemic is for public health, not medicine. We shouldn’t charge anyone to do a test! A test in a pandemic is for your neighbors, not yourself. We are off base in the US on this issue.

ARE RAPID ANTIGEN TESTS MORE LIKELY TO BE FALSE POSITIVE THAN PCR-BASED TESTS?
There’s an idea among physicians that the false positive rate of rapid tests is high, but in reality among tens of thousands of tests (in testing) there were almost no false positives. Still, there’s concern on the whole population level that false positives might arise. But the best thing about rapid tests is that they’re rapid! So if a first test is positive, take another, and confirm it in ten minutes.

I’ve seen hesitation and people saying if a rapid test is positive you have to get a PCR test, but that’s not true. Take two different rapid tests, such as Quidel’s Sofia versus Abbott. If both are positive, it’s extraordinarily likely a positive. If the tests are discordant, assume a positive, and test again 10 hours later. If it’s positive 10 hours later, that will confirm it because there will be more viruses.

WHY WILL TESTING REMAIN IMPORTANT EVEN AS MORE PEOPLE ARE VACCINATED?
I don’t think testing is going away. With longer duration from vaccination, say 8 to 10 months, could a vaccinated person transmit the virus to somebody who is susceptible? A lot of people aren’t vaccinated, for lots of reasons, so it behooves us as public health practitioners and scientists to continue to ask the question, does a vaccinated person have such low risk (of being infected) that we don’t need to evaluate if they’re positive before they interact with a vulnerable individual?

Someone in my household is unvaccinated and won’t be for awhile and is susceptible. So we still test, for an extra layer of protection. It is a 30 second test, and 10 minutes later you get the result. We might end up seeing that happen in places like nursing homes.

DO VARIANTS IMPACT TESTING ACCURACY?
Unfortunately the rumor mill has run, and it even hit the commissioner of the FDA who misspoke on NPR and said rapid antigen tests, like the Abbott test, are more likely to be affected by variants. That’s not true.

Any of these tests can potentially succumb to a variant. If you get a mutation right where the PCR test targets and is supposed to bind, you can lose the PCR signal. That’s one of the ways we first saw the B.1.1.7 variant circulating. In a triple target test that binds to 3 different parts of the virus, one was dropping out. That was a variant. (This phenomenon of the absence of binding revealing the variant is called “S gene dropout” or “S gene target failure.”) The silver lining is that (S gene dropout) allowed us to detect the B.1.1.7 variant, and that kicked off new sequencing efforts.

Any of the tests can potentially lose efficacy if the variant mutates just at the right spot. But so far we haven’t seen a lot of examples of that with a major impact, and no tests are particularly susceptible to new variants. If that occurs, it’s more difficult to create a new antigen-based test than to just find new PCR primers and create a new PCR test.

HOW ARE DEMOGRAPHICS CHANGING FOR WHO GETS SICK?
Ontario is seeing a rise in infection, with more younger people getting sick. Older people are not getting as sick anymore because they’re vaccinated, so it’s hard to parse out. But evidence is building that the virus is going to mutate, or has already mutated, to impact younger people more than it was. We’re watching that; why it happens isn’t clear.

But there’s serious concern that variants could start impacting younger people more. If so, we have to accelerate vaccines and the media campaigns to ensure younger people are able and willing to get vaccinated. Many have been hesitant to get vaccines.

WHAT IS THE RISK OF A FULLY VACCINATED PERSON BEING INFECTED WITH A VARIANT?
Consider 3 things: exposure, getting infected, and then infection with consequence.

For exposure it doesn’t matter if you’re vaccinated or not vaccinated, that part’s behavioral. Whether virus can grow in you is part of the continuum of being infected.

A vaccinated person might still be able to harbor some of the virus, which could be a good thing because it gives the immune system a reminder, a boost. The question really refers to whether a fully vaccinated person can get sick.

All vaccines confer nearly 100% protection against the most severe outcomes, and that’s the most important part. If vaccinated, it is very unlikely you will get severe disease even if you’re exposed and infected with this virus.

WE’RE ABOUT TO ENTER A SUMMER LULL. WILL COVID ROAR BACK IN THE LATE FALL AND WINTER?
Last year in April, we were thinking about reopening, and I said we have to focus on ensuring we have the pieces in place to not allow surges in the winter. This year I’d say the same.

In fall and winter, even with most adults vaccinated, we should anticipate continuing to see small surges of cases. Along with those, I’m concerned that we will see small surges seeded and driven by younger people bleeding into older age classes and causing infections and maybe even deaths. Some older individuals who are furthest out from the vaccines might have a weakened immune response and protection.

So we have to be start conditioning society to understand that this is possible and make plans to how we will respond. At what level does it warrant another shutdown? Does it warrant not giving kids vaccines and putting energy into providing boosters for the elderly? We need to ensure that when small outbreaks and surges happen in the fall and winter, we have a game plan in place.

AND THAT LEADS BACK TO TESTING TO CONTROL THE COMING NARRATIVE…
It makes sense to have rapid testing programs ready to go. We don’t have to use them twice a week between now and then, but we can have them in place in case transmission resurges in the community and we need to start testing again.

We need to condition society to know how to use the rapid tests to keep the reproduction number below 1. We can’t rest on our laurels now and assume COVID is gone. We might be kicking ourselves come fall or winter, although vaccines mean that everything then will be less severe.

Maybe our decision as a society will be that even if there is a small rise in the number of cases, we consider it like the flu and don’t make large changes. We have to have that conversation now to decide at what level are we comfortable? If it’s at zero deaths, we have to prepare to make significant changes. But if .001% is acceptable, maybe we’ll be just fine.

The point is that the virus isn’t going away entirely. It is shifting dramatically in our favor as a result of vaccines, but we could have a new variant tomorrow that really does break through our immunity.

We have done a bad job, except in developing the vaccines, of looking 6 to 8 months out and asking what will we do then? We have the capacity to do that and we can start preparing the playbook now so we’ll know how we’ll want to respond given different scenarios.