At-Home COVID-19 Tests: How They Perform, And What Clinicians Should Know

Editor’s note: The FDA granted emergency authorization to a fourth at-home COVID-19 test on March 5, following the publication of the Curbside Consults article and, as such, is not summarized here. According to a press release issued by the Food & Drug Administration, the Cue COVID-19 Test for Home and Over The Counter (OTC) Use is the first molecular nucleic acid amplification test intended to detect genetic material from SARS-CoV-2 virus present in the nostrils. It is also the first molecular test authorized for at-home use without a prescription.

The Food and Drug Administration’s emergency use authorization of at-home COVID-19 tests will undeniably change the diagnostic paradigm for COVID-19, enabling greater access to tests and results. A team of Cleveland Clinic experts considers the clinical implications of this in an article published in the Cleveland Clinic Journal of Medicine’s Curbside Consults.

At the time of publication, three at-home COVID-19 tests have been authorized — one that uses an isothermal amplification assay, while the other two use antigen detection. The authors review the advantages and disadvantages of these tests based on the submission data that was reported to the FDA.

Making the distinction: Isothermal amplification tests versus antigen detection tests

At present, the Lucira COVID-19 All-In-One Test Kit® is the only isothermal amplification assay with FDA emergency use authorization for home use. The authors explain that isothermal amplification methods use helicase or other enzymes to separate the two strands of DNA. This is in contrast to reverse transcription-polymerase chain reaction (RT-PCR) tests, which use thermal cycling equipment for this amplification. The Lucira test requires a prescription and, is currently only cleared for use on symptomatic individuals at home or in a clinical setting.

How accurate is it? Data submitted to the FDA had results on 101 specimens from symptomatic individuals. Fifty-one of these individuals were infected with the SARS-CoV-2 virus as determined by RT-PCR testing. The data show a 94.1% positive percent agreement with an RT-PCR test across all cycle threshold values and a 98% negative percent agreement when compared with control testing. Notably, results showed 100% positive agreement after samples with low levels of virus, no longer reflecting active virus, were eliminated.

The Ellume COVID-19 home test is the first antigen detection test to receive FDA emergency use authorization. This assay, which detects the SARS-CoV-2 nucleocapsid antigen, will soon be available over-the-counter without a prescription. After the individual conducts a nasal swab, the results are transmitted to a smartphone app and also relays results to public health officials through a HIPAA compliant process.

How does it perform? Of the 198 specimens submitted, 37 were shown to contain SARS-CoV-2 by way of RT-PCR testing. The Ellume test detected 35 of the 37 positive specimens (94.6% positive percent agreement). The authors note that were five false-positive reactions, and all occurrences of such were in asymptomatic individuals.

BinaxNOW COVID-19 Ag card home test is the second antigen detection test authorized for home use. It integrates BinaxNOW COVID-19 Ag Card – used currently in healthcare settings – with a smartphone app and eMed, an internet electronic care delivery service that helps facilitate specimen collection and HIPAA compliant reporting.

The authors outline the submission data for this test’s performance, both at home and in a healthcare setting. For the at-home cohort, of 52 individuals — all within seven days of symptom onset – 24 individuals tested positive with RT-PCR testing. When all cycle threshold values were controlled, the test had an overall 91.7% positive percent agreement and a 100% negative percent agreement with the RT-PCR tests. However, performance increased to 100% positive percent agreement for those with cycle threshold values of 33 cycles or less. This indicates they were early in the progression of the disease, explain the authors.

As for the test card performance in a clinical setting, the data included 460 patients across 10 clinical sites. For those within a seven-day window from the onset of symptoms across all cycle threshold values, there was 84.6% positive percent agreement and 98.5% negative percent agreement. The authors say that performance improved to 95.6% positive percent agreement when controlling for individuals within seven days from the onset of symptoms and with cycle threshold values of 33 cycles.

Examining the advantages and disadvantages

There are obvious advantages associated with the ease and accessibility of these tests, the authors argue. Putting it into context, an individual can receive test results generally between 15 to 30 minutes from the safety of their own homes, as compared to traveling to a facility and waiting several days for results from a commercial reference lab. The reporting function, a feature of two of these tests, is also important from a public health perspective.

The chief disadvantage or limitation of at-home tests is ensuring a quality specimen, say the authors. Manufacturers have tried to simplify the specimen collection process, however, it’s ultimately up to consumers to follow collection guidelines. A poor quality specimen, regardless of test type, translates to poor quality test results, they say.

At-home COVID-19 tests: Are they accurate?

The authors argue that the sensitivity and specificity of the assays are significant issues for COVID-19 home tests. Isothermal amplification assays and antigen detection tests are not as sensitive as RT-PCR assays. And while they appear to perform well when tested on specimens from symptomatic individuals, they say a negative test from a symptomatic individual should be confirmed by another test.

Another issue – at-home tests tend to underperform in asymptomatic populations, with the potential to generate a false-positive reaction. Adding to this, the viral load of the disease usually peaks right before an individual is symptomatic. Therefore, a positive result from an asymptomatic individual could be a false-positive or a true-positive, either way, it warrants further testing.

To read the Curbside Consults article in its entirety, visit the Cleveland Clinic Journal of Medicine.