Antibody testing will be key—once we understand what the results mean

Antibody testing will be a key tool for answering those questions, according to senior government officials, pharmaceutical industry veterans, and academic experts who spoke with Fortune. But, as with everything linked to this insidious scourge, it’s complicated. It will take time to parse the information and develop the appropriate regulatory guidance we need to figure out which tests work best—and what, exactly, they’re telling us about the nature of the coronavirus and immunity to this pathogen.

The ‘Wild West’ of antibody testing gets a checkup

The key question for any diagnostic is fairly straightforward: Does this thing actually work? But answering it is, frustratingly, trickier than you might think. And in the midst of a pandemic, regulators have to balance the need to rush experimental tests to patients while also gauging their efficacy.

The Food and Drug Administration (FDA) has granted emergency authorization to a dozen COVID-19 antibody blood tests to date. The initial carte blanche approach has elicited criticism from the medical community, with some warning of a “Wild West” scenario that may galvanize snake oil salesmen and leave the public with inaccurate information.

More than 70 companies have flocked to the gold rush that is developing experimental COVID-19 antibody tests, which can be conducted more easily than other types of coronavirus diagnostics. Emergency authorizations come with a lower scrutiny level than full approvals or clearances under regulatory guidelines, two senior FDA officials explained.

Other kinds of coronavirus tests, including so-called polymerase chain reaction (PCR) technology, often require a nasal or throat swab (or both) and take longer to conduct. They may require very specific equipment at specialized labs. These tests can tell medical professionals if someone has an “acute infection”—if the virus is actively circulating in their system.

But antibody tests are serological tests that can be done with a simple blood draw and help determine if someone has had a previous COVID-19 infection they’ve recovered from. Someone who has recovered could, theoretically, safely return to work or go out in public without risking spreading the coronavirus to more vulnerable people.

The trouble is we’re still not sure just what the presence of coronavirus antibodies means. Would they suggest immunity for up to two years, as was the case with most patients who contracted SARS, a different type of coronavirus? Or might it be a shorter immunity period? There have been reports that some patients have re-tested positive after initial infection, though it’s unclear whether that’s due to an initial false positive result. And which companies’ tests, specifically, will provide the most accurate information?

“One of the challenges is that it’s a new virus,” says Natalie Dean, an assistant professor of biostatistics at the University of Florida and expert in epidemiology. “What’s probably going to happen is there’s going to be some level of immunity, but we don’t know for how long. We’re going to have to do followups of patients over time for antibodies.”

In the case of antibody tests, this presents a chicken-and-egg dilemma, according to the senior FDA officials. The agency’s initial focus in March was on providing widespread access to antibody tests. The officials emphasized that far more data would be required for diagnostics in a non-emergency situation.

The FDA updated its initial March guidance for antibody testing earlier this month in an effort to crack down on companies making misleading claims and to clarify its quality control responsibilities.

“At the time we issued our March 16 policy, a higher level of flexibility was appropriate for antibody tests than for molecular tests that detect the presence of the virus that causes COVID-19, since antibody tests are not meant for use to diagnose active SARS-CoV-2 infection,” wrote regulators in a public statement in May, adding that more than 200 antibody tests are going through the pre-emergency authorization or authorization process. They also stated that the FDA is working with the National Institutes of Health (NIH) and Centers for Disease Control (CDC) to determine how effective certain tests are.

Back in April, many of the antibody tests hitting the market hadn’t even received FDA authorization, much less a wider accounting of their accuracy.

What are the most promising antibody tests?

New York City, the epicenter of the pandemic, has launched a free and widespread antibody testing effort that could reach up to 140,000 residents. The trouble is that even if coronavirus antibodies ultimately confer immunity for some time, testing can’t become a reliable tool for getting people back to work unless there’s a baseline of how effective such tests are.

There are two key metrics to determining the accuracy of an antibody test. The first is something called “sensitivity”—this is a measure that tells you how accurate a test is in identifying people who actually have antibodies and thus have been exposed to infection (otherwise known as the the true positive rate). The second is “specificity,” which provides the flip side of the data—who doesn’t have antibodies.

“Sensitivity is sensing those who have been sick, specificity is spotting the lack of past or recent infection,” says Alan Wright, the chief medical officer at Roche Diagnostics, which claims to have one of the most accurate COVID-19 antibody tests cleared for emergency use.

Roche has said that its diagnostic has a staggering 100% sensitivity rate and a more than 99.8% specificity rate. Rival Abbott Laboratories has received two emergency authorizations with similar accuracy claims for its own antibody test.

FDA officials and Roche’s Wright underscored the importance of using a combination of tests—and sharing data across agencies—to truly understand the scope of immunity and the infection rate across the public. In the past few months, a team of researchers from UC Berkeley, UCSF, and other academic institutes have been working to validate the accuracy of tests on the market with decidedly mixed results.

“This is part of a suite of tests,” says Wright. “We don’t approach diagnostics in isolation.” For instance, the sensitivity and specificity of an antibody test such as Roche’s may have to be done several weeks after an initial coronavirus PCR test which confirms an active infection.

The accuracy of these tests will also help inform drug makers of the best approaches to COVID-19 drug and vaccine development. Longer-term data about immunity and the staying power of COVID-19 antibodies may spell the difference between a one-time vaccine like with measles or a seasonal one such as influenza. But that process will take even longer to play out.

“There are two components to approval for a diagnostic,” says Wright. “One is analytical evidence, or just general data-gathering. The other is clinical evidence that can fuel the drug development process and tell us more about immunity and the virus’ long-term effects on the health system.”

Those are fundamental aspects of understanding a new pathogen. “Antibody tests give us a bigger picture of the range of disease,” says Dean, the biostatistician. “They’re especially useful for identifying high-risk groups. [They] let us see at the highest-risk occupations such as factories where people are in close quarters. But you have to piece these things together from a bunch of different sources.”