Daily antigen tests hailed as game-changer by Big Ten

When the word “game-changer” comes out of a coach’s mouth, it’s usually about a gun-slinging quarterback or a terrorizing pass-rusher.

On Wednesday, Indiana football coach Tom Allen linked that term to something no one could have imagined before the COVID-19 pandemic.

“The rapid antigen testing that we’re now requiring, it was a game-changer,” Allen said. “It’s completely changed from where we were at five weeks ago. We didn’t have that in place.”

A month ago, the Big Ten’s fall football season was no more, because chancellors and presidents didn’t believe it could be played safely. Now, a capability powered by virus proteins and antibody detectors has saved the day.

In basic terms, an antigen test is appealing because it’s employed daily. The results appear in 15 minutes. In comparison to the polymerase chain reaction (PCR) tests the Big Ten utilized for twice-a-week testing, a daily test brings college athletics closer to a “bubble” environment.

Of course, there is more to it. A lot more. And Dr. William G. Morice, a professor of laboratory medicine and pathology at the Mayo Clinic, can help explain the makings of this game-changing application in more detail.

Although, he must add some realistic expectations.

“No. 1, the Big Ten’s approach is very thoughtful and it does seem to place the safety of the student-athletes as paramount. I think it’s well laid out,” Morice said. “But the second point is that no test is perfect, right? We’ll just have to wait and see. Unfortunately, there is nothing that’s going to be foolproof in guaranteeing that it’s going to keep athletes COVID-free.

“But I think what they’ve come up with as good of a plan as can be.”

Antigen vs. PCR

To examine how the antigen test changes the equation for Big Ten teams, let’s first start with where football programs were five weeks ago.

Why weren’t they using antigen tests?

Because PCR has been considered the “gold standard” test for COVID-19, as Morice put it. Unlike an antigen test, which uses antibodies to detect virus proteins, a PCR test searches for genetic material from the virus. So it’s much more precise.

It costs a pretty penny — about $100 a test — to send the sample off to a lab, initiating a heating and cooling process to “amplify” it. Essentially, a chain reaction makes the sample larger and its DNA more detectable. But it takes days, not minutes or hours, to finish that process.

On the plus side, the nucleic acids being studied in a PCR test are incredibly stable. That’s not always the case with the bits being studied with an antigen test.

“That’s how they carbon date people, they get DNA out of skeletons and bits of dirt and everything else,” Morice said. “The antigen test is much more prone to the specimen decaying or falling apart. … If someone gives you a nasal swab and they leave it on top of the bench for 10 minutes and someone runs a test, it may not perform as well, because, in those 10 minutes, you might have lost some of the antigen. Because it’s broken down.”

But running a result through a lab also has obvious disadvantages, mainly slow turnaround times. Especially in areas with high testing demand. That was too often the case early in the pandemic, making it impossible to immediately isolate virus-spreaders. Even in August, the Big Ten was worried about the ability of all 14 schools to uniformly test and contact trace with PCR tests.

Antigen tests were the obvious solution. They are less expensive, point-of-care tests — often compared to pregnancy tests. But they weren’t exactly trustworthy.

A person could be tested early in an infection, and there just isn’t enough virus in a person’s nasal cavity to easily detect it, producing a “false negative” result. An antigen test could also be designed to be more “sensitive” to lower levels of the virus but produce more false positives, because it’s reacting to non-COVID proteins.

A balance between sensitivity and specificity has troubled antigen test producers. Getting that right took time.

So what’s changed?

Investment. Lots of it.

“Billions of dollars were invested in trying to create and improve the antigen test at the onset of the pandemic, because of its potential to be widely deployed, and it gives you an answer right away,” Morice said. “So you can act right away if you have COVID.”

Morice, who works with the World Economic Forum, says antigen tests will be especially valuable in less wealthy countries where healthcare infrastructure isn’t as robust. It’s a point-of-care product. It just needs to be sensitive enough to identify asymptomatic COVID-19 carriers.

In late August, Abbott Technologies unveiled a $5 antigen test, approved by the Food and Drug Administration, purported to detect COVID-19 with a sensitivity of 97.1 percent and a specificity of 98.5 percent. The test managed that in the first seven days of patients’ onset of symptoms. Other companies were beginning to advertise similarly promising results, as well.

Morice calls such a high rate of accuracy in newly developed products “remarkable,” because the average antigen test usually has sensitivity percentages in the 80s rather than the 90s.

But these results are not out of the realm of possibility.

“There are tricks. There are ways you can try to make the protein more readily detected,” Morice said. “I’m sure they have something that’s propriety. You can try a similar type of chain reaction, but in a much different way than for the PCR. There are ways to try and amplify the signal, basically. Often times, those make it less specific, though.”

That’s where Morice drifts into words of caution.

While the results provided to the FDA for validation are promising, there is a chance these antigen tests will not perform as promised under real-world pressures. For instance, did Abbott truly test people who were early in an infection — people with minimal amounts of virus in their nasal cavity? And how well will Abbott’s equipment truly hold up in a non-controlled environment?

“Sometimes the thing they have creatively done to make the test work better in a controlled setting is a thing that may not work as well outside,” Morice said. “They don’t realize if the cartridge gets left out in the sun it breaks down. There are things like that that can happen.”

It’s just too early to tell. But that’s why Morice thinks it’s smart that the Big Ten is adding a PCR to confirm results for athletes who test positive via antigen.

Morice would also recommend the league have any athletes exhibiting symptoms skip straight to a PCR test because it’s still more trustworthy.

“I wouldn’t be surprised if that’s already in the Big Ten’s protocols, as well,” Morice said.

The potential

No test is perfect. Ohio State team physician Dr. Jim Borchers admitted as much during the Big Ten’s unveiling of a fall football plan, saying he couldn’t say with 100 percent certainty that COVID-19 won’t be transmitted during teams’ practices and games.

“But we feel confident with (daily testing) we can make our practice and competition environments as risk-free as we possibly can,” Borchers said.

In other words, as close to a game-changer as possible.

More sensitive antigen tests give the Big Ten a chance at identifying and isolating infected athletes before they spread the virus to others. Daily testing also provides more opportunities to root out asymptomatic spreaders. In theory, that could prevent the kind of outbreaks that sideline large chunks of teams from week to week.

Not long before the Big Ten’s announcement, IU athletic director Scott Dolson was expressing optimism about advancements in daily testing. The Pac-12 had already reached an agreement with Quidel Corporation to implement antigen testing for its athletic programs.

Dolson was characterizing fall sports in the Big Ten as a “when” proposition, not “if.”

“It’s amazing, just in testing alone, how in a relatively short time period, how quickly things advanced,” Dolson said last Friday. “I’m certainly optimistic and hopeful.”

Only a few days later, cautious optimism turned to reality. While the Big Ten hasn’t specified which companies are supplying its antigen tests, Iowa AD Gary Barta added Thursday that the conference has “handshake agreements” with multiple suppliers.

IU was ahead of the curve in securing its own antigen tests, allowing the football program to begin daily testing this week. Once the conference starts mandatory daily testing Sept. 30, IU will switch to the Big Ten’s tests.

“It creates somewhat of a bubble … and you’re going to know that you’ve got a clean practice area to be in, or watching film, or anything you do with your team,” Allen said. “The same thing, the teams you are going to play are going to be in the same boat.”

Everyone hopes there are enough guardrails in place. If a player tests positive, he will have to sit out 21 days. That’s two weeks to isolate but also a week for cardiac screening and getting the athlete back in shape.

The Big Ten will also maintain a cardiac registry to study the effects of COVID-19 in athletes’ hearts.

Morice, who earned his bachelor’s in biochemistry from IU in 1987, sees his alma mater and its fellow Big Ten teams as being on the front lines here. They will help determine how effective these antigen tests really are, especially considering the Big Ten intends to test all sports daily.

“There will actually be a big benefit to the medical community from the Big Ten’s approach,” Morice said. “They will be doing so much of it, we’ll get a real-world comparison of how this is working versus the PCR.”

One comment

  1. I have posted before that fast, accurate, quick results, and inexpensive testing would make football and other sports possible. The medical follow up will be key to completing a full 9 games. I hope the plan works!

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