To the Editor—Judging effectiveness, managing positives, modifying quarantines, and advising regarding negatives1 require realistic expectations of COVID-19 rapid antigen tests (RAgTs) because their performance is limited. The government is supplying 1 billion of these tests to Americans (at COVIDtests.gov), empowering people to discover if they are infected by performing self-testing. Will schools and workplaces accept the results, perhaps by requiring photographic or telehealth proof? Hopefully officials will embrace this advance in point-of-care testing, including home molecular diagnostics (Table), and determine its impact for a world striving to mitigate the effects of an endemic disease, avoid lengthy quarantines, and limit lockdowns.
The authors of a recent commentary2 state, “For symptomatic patients, antigen testing achieves sensitivities ranging from 85% to 97%,” supported by 2 references. Further, “…for asymptomatic testing, sensitivity decreases to about 74%.” However, from the start of the pandemic through the end of 2021, thirty-four publications reveal a different story. For community settings, such as drive-ups, city plaza kiosks, walk-ups, and screening centers, testing symptomatic subjects generated median RAgT sensitivity of 81.0% (range, 47.7%–96.5%) and when asymptomatic, 55.75% (range, 37%–88%). Mixed asymptomatic/symptomatic populations had a median sensitivity of 69.85% (range, 30.6%–97.6%). These medians differ substantially from the sensitivities cited in the commentary,2 while specificity medians (symptomatic, 99.85%; asymptomatic, 99.70%; and mixed, 99.5%) were in line with it.
Collating manufacturer Emergency Use Authorization (EUA) claims for home RAgTs showed a median of 86.6% (range, 85.3%–95.3%) for positive percent agreement (PPA) and 99.25% (97%–100%) for negative percent agreement (NPA). While the US Food and Drug Administration (FDA) publishes EUA PPA and NPA performance metrics in “Information for Users,” manufacturer claims typically are based on small populations that may not reflect real-world results in homes across the nation. Receiving test kits at residences implies they are for home self-testing. Searches failed to uncover validations of home RAgTs in actual peoples' hands.
Since vaccination will not stop variant infections, episodic increases in local or regional prevalence will lead to RAgT false omissions. I3 demonstrated that as prevalence increases, repeated testing can compensate for the falloff in performance due to the poor sensitivity of RAgTs. Brands containing 2 tests enable repeats (>24 but <48 hours) that improve chances of detecting infectivity. My shipment from COVIDtests.gov contained 2 kits, that is, 4 tests, so repeated testing will not be practical for most families. Omicron vaccine-breakthrough infections do not show elevated infectious viral titers in nasopharyngeal swabs as compared to Delta,4 but persistent infectivity heightens Omicron transmission. COVID-19 tests should be validated for variants and labeled as such on packaging for consumers.
Since the performance of RAgTs generally is limited, we should consider alternatives during this national experiment. Manufacturers of reverse-transcription loop-mediated isothermal amplification (RT-LAMP) home tests boast PPAs ranging from 90.9% to 97.4%, with NPAs from 97.5% to 99.1% (Table). The commentary2 did not highlight these home molecular diagnostics or their better performance, which could obviate repeating RAgTs. However, the downside of home molecular diagnostics is their higher cost. Therefore, they should be part of the subsidized national distribution. Additionally, their performance in homes should be studied systematically and compared to the performance of RAgTs.
Multidisciplinary public health teams can collaborate in a “Grand Challenge” to study the impact and cost-effectiveness of RAgT, RT-LAMP, and other diagnostic technologies as they emerge for self-testing by partitioning part of the government supply of COVID-19 tests into studies of performance conducted in diversely populated geospatial regions.5 Fact-based point-of-care social innovations will bring higher diagnostic standards, so we can be guardians of our own health, as well as the well-being of our families, and the safety of communities where we live, now and in future public health crises.