IDSA Re-examines Role of Antigen Testing for SARS-CoV-2 at This Point in Pandemic

Damian McNamara

June 03, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Dr Kimberly E. Hanson

The need for speed led to widespread adoption of antigen testing for SARS-CoV-2 last year. However, now that the COVID-19 pandemic has evolved, the role for such testing is changing as well, new guidelines from the Infectious Diseases Society of America (IDSA) suggest.

Not to be confused with antibody testing — or the body's immune response to SARS-CoV-2 infection — antigen testing detects proteins from the actual virus. Ideally, in an infected person a nasal swab collects enough of these proteins to yield a positive result.

"The benefit of point-of-care rapid antigen testing is it's it'll generate results potentially while an individual is present and in front of you. You can make informed decisions about how you want to manage them or the situation," Kimberly E. Hanson, MD, MHS, said during an IDSA media briefing on June 2.

In general, point of care rapid antigen assays are easier to use and less expensive than the "gold standard" nucleic acid amplification tests (NAATs), added Hanson, who is associate professor of medicine and adjunct associate professor of pathology at the University of Utah School of Medicine in Salt Lake City. NAATs are laboratory-based tests that detect viral RNA.

Hanson chaired the expert panel that created the IDSA Guidelines on the Diagnosis of COVID-19: Antigen Testing.

Dr Angela M. Caliendo

The experts conducted a systematic literature review to compare antigen testing with NAATs. "When we looked at the studies overall, what we found was that antigen tests have a sensitivity of 81% compared to NAAT in symptomatic individuals. It's even lower when you start testing asymptomatic individuals, around 50%," Angela M. Caliendo, MD, PhD, professor and executive vice chair, Department of Medicine, Alpert Medical School, Brown University, Providence, Rhode Island, said during the briefing.

For this reason, IDSA recommends using a single standard NAAT over a single rapid antigen test for asymptomatic individuals with risk for exposure.

On a positive note, antigen testing has nearly 100% specificity for detecting SARS-CoV-2.

Antigen tests perform best within 7 days of symptom onset when the amount of virus is highest in the respiratory tract, Caliendo said. The timing could explain the 50% or so sensitivity of antigen testing for detecting SARS-CoV-2 in asymptomatic people.

"By definition asymptomatic individuals don't have symptoms, so we don't really know where along the spectrum of the course of their infection that we're testing them," Hanson explained.

Testing After Vaccination

A common question concerns the role of antigen testing among people already vaccinated against COVID-19, including breakthrough cases.

For this reason, if you have a high clinical suspicion of SARS-CoV-2 infection, even in a vaccinated individual, and you get a negative antigen test result, "you should back it up with a standard NAAT test," Hanson said.

'It gets a little more complicated in asymptomatic individuals who've been vaccinated," she added.

One caveat is the panel developed the IDSA guidance at a time when highly effective vaccines were not yet available, Hanson said. "So it's likely that the role of testing will change as we see more vaccination coverage in the population."

Look at the Local Community

The local level of circulating virus is an important consideration, Caliendo said. "If you're testing someone who is symptomatic or has a high-risk exposure and the virus is circulating in the community, the likelihood that you're going to get a false-positive result is actually quite low." In this scenario, an antigen test might be more appropriate.

In contrast, when testing people without high-risk exposures in a community where the circulating virus levels are low — below 1%, for example — "then you're much more likely to see false-positive results," Caliendo said. In this case, any positive antigen test should be confirmed through NAAT.  

"Taking all of this into consideration, the panel suggested using NAAT testing over rapid antigen tests for symptomatic individuals," added Caliendo, who is also a member of the IDSA expert panel that drafted the updated guidance.

The IDSA panel also recommends NAAT when community prevalence of COVID-19 is 5% or higher.

The experts noted that antigen testing can still help identify people with SARS-CoV-2 infection when NAAT is not readily available or feasible.

Unanswered Questions

The experts considered if repeated or serial testing, even with a less sensitive assay, would boost detection of asymptomatic infection. However, they did not find enough evidence in the literature to make a call either way.

Another question is whether or not antigen tests can identify an infectious person.

"There are a couple of things to consider here," Caliendo said. For example, NAAT tests can remain positive over an extended period of time. Even though people do not have symptoms, "the RNA just hangs out there for a long time."

Building on this, the panel discussed whether a positive NAAT test coupled with a negative antigen test might be a way to determine if someone is infectious. But based on the evidence to date, Caliendo said, "you cannot determine whether a person is infectious based on antigen results."

The FDA has granted emergency use authorization to a number of at-home antigen tests. However, how well these test kits perform has not been fully studied, Hanson said.

What's Worthwhile in the Workplace

Does antigen testing make sense scientifically and economically for employers bringing people back to an office? When local vaccination rates are low and circulating virus levels are high, antigen testing could play a role in screening for positive cases.

However, when a population is highly vaccinated and the prevalence of virus in a community is low, that's an ideal situation, Caliendo said. But it's also one where antigen testing "isn't going to add a lot."

Considering the logistics and the costs involved, she added, "the juice isn't worth the squeeze."

Instead, promote vaccination in the workplace and remind people not interested in vaccination to keep their masks on at work. "I think those practices will be more helpful, more practical, and easier to implement than trying to implement testing."

Home Is Where the Test Is?

Testing technology is likely to continue to evolve as well, Hanson said. There is still a lot of interest in faster, less expensive, and sensitive testing that can be done at point of care. "Folks are working on that," Hanson said.

"The other hot topic has been testing or screening for variants," she added. Beyond identifying variants of concern that may be more transmissible, evolving strains can alter the effectiveness of monoclonal antibody therapy for people with COVID-19. She said there is a lot of interest in tracking variants for such clinical decision-making.

Advances in testing accelerated by the COVID-19 pandemic will likely lead to new diagnostic capabilities overall, including expansion of at-home diagnostics.

"You're going to see more home testing for things beyond a respiratory virus," Caliendo said. "It's amazing how quickly companies were able to figure out technically how to get that test into a little cartridge that you could purchase and bring home."

"I think the pandemic has brought out the creativity for diagnostic companies, and you're going to see more and more testing being done in the home," she added.

IDSA COVID-19 Guidelines. Published online May 27, 2021. Full text

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.

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