People trying to do the mental gymnastics to keep track of Alabama’s evolving COVID-19 statistics had another hurdle thrown at them this week with the number of “probable” cases spiking from less than 5,000 to more than 11,000 in about 10 days.
Much of that increase is being attributed to new rapid response or antigen testing that is becoming more widely available across the state.
Alabama State Health Officer Dr. Scott Harris, head of the Alabama Department of Public Health, said that probable cases in the dashboard should be considered cases as well.
“When someone says ’how many cases do we have in Alabama?’ the total of confirmed and probable is the right answer to that question,” Harris said. “We consider those all to be cases.”
Harris said those test results have the benefit of being fast and cheap, but may miss some cases that a traditional COVID test would catch. But Harris said the Alabama Department of Public Health has a high level of confidence that people who test positive with an antigen test really have the disease, and should be counted when evaluating the status of the disease.
“We believe in almost all [probable] cases that that person has COVID-19,” Harris said. “We still count them in our total and rightfully so.”
How is an antigen test different?
The “gold standard” test that has been the norm since the outbreak began is called a PCR test. The samples for antigen tests are still collected via a nasal swab, like the PCR tests. The difference is in how the lab processes these tests.
PCR stands for polymerase chain reaction, a laboratory process that amplifies the amount of virus present in a sample. That means that if a person is infected, it’s almost certain that the test will catch it. But the PCR process takes time and expensive laboratory equipment, even though it can be done on multiple samples at a time.
The antigen tests forego that process, providing results in about 15 minutes and are less expensive than the PCR tests. They can also be done just about anywhere, in any doctor’s office or urgent care facility, and potentially soon even at home, available in kits similar to home pregnancy tests.
“Antigen testing is a way to get a really rapid result using sort of very simple techniques,” Harris said.
And those rapid results, when positive, can be trusted. The U.S. Centers for Disease Control and Prevention says in its guidance on antigen testing that the antigen tests have the same level of specificity as the PCR tests. That means antigen tests are no more likely to return false positives than the PCR tests.
The drawback is that because these rapid antigen tests don’t amplify the amount of virus in a sample in a lab, people who actually have the virus might test negative.
According to the CDC, this is especially a problem later in the infection, as the patient’s viral levels may have dropped.
“Studies have shown that antigen levels in some patients who have been symptomatic for more than five days may drop below the limit of detection of the test,” the CDC said. “This may result in a negative test result, while a more sensitive test, such as RT-PCR, may return a positive result.”
The measure of how many false negatives a test produces is called sensitivity. The PCR test has very high sensitivity, meaning it’s unlikely the test will miss any cases. The first two antigen tests that were granted an emergency use authorization by the U.S. Food and Drug Administration had sensitivity of 84% and 97% compared to the PCR test.
“With every kind of test there is, there’s always some kind of trade off,” Harris said. “And so this test is less expensive and it’s a lot quicker, but it’s a little bit less sensitive than the PCR test.”
Tests could miss people who have COVID
Dr. Jeanne Marrazzo, director of the Division of Infectious Diseases at the University of Alabama at Birmingham said the positive results from antigen tests could be trusted, but said the tests may miss people who have the virus but are not displaying symptoms.
“If you have a probable test by one of these antigen tests, by and large, I think you can believe it,” Marrazzo said. “There could be a new antigen test that comes out tomorrow that makes me a liar, but in general, I think you can believe it.”
Marrazzo also said she would like to see more data on how well the antigen tests performed on people who were not displaying symptoms.
“We don’t have any data on how that test performs in somebody without symptoms, and yet it’s being used widely for screening,” Marrazzo said. “Do I think it’s good? Yeah, I do think it’s good because you can probably believe a negative test, but we don’t know.”
Marrazzo also said that the U.S. Food and Drug Administration has granted emergency use authorizations for several antigen tests, so it’s hard to keep track of the effectiveness of them all.
“It’s really complex, because first of all, not all of these tests are created equal,” Marrazzo said. “One of the challenges with the FDA’s recent behavior has been they’ve granted emergency use authorizations to so many tests that we really don’t have a clear handle on what their performance characteristics are.”
Why positive tests are counted as ’Probable’
So why are Alabama’s positive antigen tests reported as probable and not confirmed, when they’re as accurate as the standard PCR tests?
Harris said that’s due to guidance from the CDC and the Council of State and Territorial Epidemiologists to keep data standardized across states even as testing for the disease has evolved.
“This has caused a tremendous amount of confusion and unfortunately, it really just has to do with the technical language used by epidemiologists,” Harris said. “A probable case is not a case that we have less confidence in the diagnosis. It’s simply a way that we count cases and make sure we’re comparing apples to apples from one state to the next.”
The original idea was that people who test positive on the antigen test would get a PCR test to confirm, but with PCR tests still subject to limitations, that’s not always possible or the best use of limited supplies.
“Technically right now, if you get a non-PCR test, you’re supposed to confirm it with PCR to actually make sure that it’s a confirmed case,” Marrazzo said. “Now, that’s not feasible number one, and number two, it defeats the purpose [of having a rapid test].”
Antigen testing is different from antibody testing
Though they may sound similar, antigen testing is very different from antibody testing. Antigen testing uses a nasal swab and looks for antigens, which are found on the virus itself.
Antibody tests are blood tests, which look for antibodies, substances made by our immune system to fight the virus. Antibodies can still be found in the bloodstream for some time after the virus has already cleared (though it’s not clear how long yet in the case of COVID-19), so a person can test positive on an antibody test long after they have recovered from the disease.
In short, a positive antigen test says you have COVID-19 now and could potentially spread it to others. A positive antibody test means you had COVID-19 in the past and may or may not have already recovered from it.
Antigen testing to increase
Alabama State Epidemiologist Sherri Davidson said the because more different facilities are administering these antigen tests, data reporting has been a challenge. Facilities like urgent care centers or nursing home that aren’t used to running lab tests have not always reported results to the department in a timely manner. That makes it harder to keep a timely and accurate count of how many people have tested positive, she said.
And the number of antigen tests in Alabama is almost certain to increase in the coming weeks. Harris said the federal government is working to provide these rapid response tests to states and that Gov. Kay Ivey will determine how Alabama will use those tests once they arrive.
Harris said that could further change the data flowing into ADPH’s dashboard to measure the outbreak.
“What it will tend to cause, as more and more people use these antigen tests, like the ones being shipped to schools or shipped to nursing homes, is that you’ll see the decrease in the number of PCR results, which can be confirmed cases, and a higher number of probable cases which comes from using the antigen tests,” Harris said.