Dive Brief:

• Harvard and Yale physicians have called for urgent assessment of the sensitivity of coronavirus diagnostics in asymptomatic people to stop false negatives hindering efforts to safely reopen the U.S. economy.

• In a paper published in the New England Journal of Medicine Friday, the authors call for development of a reference standard for measuring the sensitivity of COVID-19 tests in asymptomatic people who may not be isolated and can potentially infect others.

• NEJM posted the paper on the same day it published a separate report arguing the World Health Organization is “dead wrong” to wait for certainty before supporting the use of antibody tests to determine if an individual can return to work.

Dive Insight:

The NEJM papers illustrate the challenges facing organizations that develop and use COVID-19 tests. As many strategies for ending lockdown restrictions rely on some form of testing, there is pressure to move as quickly.

The paper authored by researchers at Harvard Medical School and Yale University makes the case for caution, noting concerns about reliability of products that test for active infections with the SARS-CoV-2 coronavirus.

Abbott’s rapid diagnostic test has been the subject of several studies raising concerns about its false negative rate, leading the company to issue new data last month. Abbott argued the data show its test is performing comparably to alternatives, although it acknowledged it performs better shortly after emergence of symptoms. 

The fear is that if a test erroneously delivers a negative result, an individual may continue interacting with people in the belief they are not infectious.

Taking a cautious approach to negative results in patients with symptoms consistent with COVID-19, for example by testing them again, could help. However, that approach will fail to stop asymptomatic spread. 

One study found 57% of people testing positive at a nursing facility had no symptoms at the time of testing. Frequent testing could identify such people before they spread the virus, but only if the rate of false negatives is low. As it stands, it is unclear how COVID-19 tests perform in asymptomatic patients. The NEJM authors want that to change.

“Designing a reference standard for measuring the sensitivity of SARS-CoV-2 tests in asymptomatic people is an unsolved problem that needs urgent attention to increase confidence in test results for contact-tracing or screening purposes. Simply following people for the subsequent development of symptoms may be inadequate, since they may remain asymptomatic yet be infectious,” the authors wrote.

The other NEJM paper looks at the pros and cons of antibody tests, which identify evidence that an individual has previously been infected with SARS-CoV-2. It is unclear if anti-SARS-CoV-2 antibodies confer immunity against the virus, leading organizations including WHO to argue there is insufficient evidence to use positive test results to support the lifting of restrictions on individuals.

While acknowledging the uncertainties, the NEJM authors, some of whom also work at Harvard and Yale, think the impact of the “raging pandemic” and actions taken to curtail its spread justify acting on incomplete information.

“The costs of delaying any reopening until we are certain that no one returning to work will transmit COVID-19 are also real. There is no such thing as a 100% safe bet. Let’s not permit an unattainable ideal to be the enemy of a very good option that we currently have,” the authors wrote.

One concern with antibody tests is, even if they do indicate immunity, their imperfect accuracy could cause them to do more harm than good, for example by delivering a false positive that emboldens someone to act as if they are protected against the virus. 

FDA is working with the National Institutes of Health to address that concern by supporting independent assessments of antibody tests. Having assessed five antibody tests, the agency has identified three kits from BioMedomics, Phamatech and Tianjin Beroni Biotechnology that should not be distributed. In populations in which 5% of people have antibodies, the positive predictive values of the withdrawn tests were as low as 42.4%.

A test promulgated by BD, developed and manufactured by partner BioMedomics, was available through the medtech starting in late March. However, BioMedomics has "voluntarily withdrawn" its test from the market, according to FDA.​