On November 10, 2021, the US Food and Drug Administration (FDA) announced a class I recall, “Potential for false positive results with certain lots of Ellume coronavirus disease-19 (COVID-19) home tests due to a manufacturing issue.”1  False-positive results indicate coronavirus 2019 (COVID-19) infection when there is none. The recall affected 2 212 335 tests sent to retailers April through September 2021. One can identify affected lots by visiting the Ellume Web site.2 

False positives can precipitate unnecessary treatments; place healthy persons in confinement with those infected, increasing the risk of contracting COVID-19; distract health care providers from life-threatening conditions and delay critical therapies; activate public health restrictions; discourage families from visiting the elderly; cause disregard for vaccinations; and force quarantine on workers, teachers, performers, and others who miss the opportunity to serve the public and earn their living.

The performance of the Ellume rapid antigen self-test was illustrated in Figure 8, “First Over-the-Counter Fully at Home Antigen Diagnostic Test for COVID-19,” published online March 8.3  That figure compared asymptomatic versus symptomatic individuals and illustrated striking statistical uncertainty (large 95% CIs) in low and high prevalence. The test displays a range of relatively good performance from 30% to 50% prevalence, notwithstanding manufacturing issues revealed by the FDA in the recall.1 

There are several lessons to learn from this experience. Firstly, the FDA issued the recall not because of direct harm by the test itself, but because of the potential consequences of false-positive results, a valuable general principle. The FDA cited 35 false positives, no reported deaths, and stated, “The reliability of negative test results is not affected.”1  Nonetheless, that does not mean there are no false negatives.

A negative antigen test is not license to gather, mingle, or work without precautions that prevent COVID-19 contagion. Figure 6 from the same paper3  shows striking fall-off in the performance of antigen tests caused by low sensitivity as prevalence increases.

The FDA database of nonprescription home COVID-19 antigen tests4  shows a median positive percent agreement (PPA) of 86.6% (range, 83.5%–95.3%) and a median negative percent agreement (NPA) of 99.25% (range, 97%–100%). Home tests granted Emergency Use Authorization (EUA) from October through December had PPAs and NPAs of 85.7% to 94.3% and 98.1% to 100%, respectively, whereas most had PPAs <90%. The FDA announced November 15 that it intends to focus more on at-home tests to increase their accessibility, but performance must be improved. The FDA should but has not tightened PPA EUA thresholds.

Dubbed the “contagiousness test,” an antigen test works best when the viral load is high and now is recommended right before an event rather than the day or night before. However, variant viral dynamics increase diagnostic uncertainty. Emerging research will reveal when Omicron peaks, show how high infectious viral titers rise, and explain increased transmissibility.

In view of the rapid spread of the Omicron variant, the White House promised 1 billion free home tests distributed directly to the public by mail through the COVIDTests.gov Web site, reimbursement of purchased at-home tests by insurance, and new federal testing sites around the country.

With vaccinations unable to stop infections and prevalence increasing, one must be vigilant for false negatives, especially if the patient is symptomatic, in which case a confirmatory molecular diagnostics test is indicated. Some home kits include 2 tests. Mathematic analysis of positive and negative predictive values as continuous functions of prevalence shows repeat antigen testing can improve performance significantly.5 

A single negative antigen test can gateway return to the United States from foreign travel, but 2 sequential negative tests would decrease risk and false omission rates while improving predictive values.5  Schools, universities, and other organizations recognize the value of testing twice. They are requesting repeat antigen testing 1 and 3 days before returning from holidays, and if a positive test result or symptoms are present, then the patient should quarantine rather than return, and possibly undergo retesting to leave quarantine.

Precautions are necessary going forward, because the United States intends to fund billions of dollars for rapid antigen tests and accelerate FDA authorization. Home testing encourages empowerment, and self-testing should be accompanied by education. Health care providers and those using home tests should consider the likelihood and impact of both false-positive and false-negative results by confirming clinically suspicious findings with high-sensitivity molecular diagnostic tests that can both rule out (high sensitivity) and rule in (high specificity) COVID-19.

1.
Ellume recalls COVID-19 home test for potential false positive SARS-CoV-2 test results.
US Food and Drug Administration Web site
.
December
20,
2021
.
2.
Ellume COVID-19 home test voluntary recall.
Ellume Web site
.
December
20,
2021
.
3.
Kost
GJ.
The impact of increasing prevalence, false omissions, and diagnostic uncertainty on coronavirus disease 2019 (COVID-19) test performance
.
Arch Pathol Lab Med. 2021;
145
(7)
:
797
813
.
4.
In vito diagnostics EUAs–antigen diagnostics tests for SARS-CoV-2 (home tests).
US Food and Drug Administration Web site
.
December
20,
2021
.
5.
Kost
GJ.
Diagnostic strategies for endemic coronavirus disease 2019 (COVID-19): rapid antigen tests, repeat testing, and prevalence boundaries
.
Arch Pathol Lab Med.
2022
;
146
:
16
25
.

Author notes

The author has no relevant financial interest in the products or companies described in this article.