SARS-CoV-2 antigen tests exhibit moderate-to-high sensitivity vs RT-PCR, cultures

Home antigen tests for SARS-CoV-2 infection were moderately sensitive compared with RT-PCR* test but highly sensitive compared with viral culture in adults and children with RT-PCR-confirmed infection, a prospective study suggests.

“[Our findings show that] antigen test sensitivity was 50 percent during the infectious period, 64 percent compared with same-day RT-PCR, and 84 percent compared with same-day cultures,” said the researchers.

The antigen test sensitivity was below the WHO target for point-of-care tests (80 percent), but the researchers noted that this was not negatively associated with self-collection. [www.who.int/publications/m/item/covid-19-target-product-profiles-for-priority-diagnostics-to-support-response-to-the-covid-19-pandemic-v.0.1, accessed May 25, 2022] “Although antigen test use errors were commonly observed, these were not associated with reduced test accuracy,” they said.

“The frequency and timing of home antigen testing affected the sensitivity to detect cases,” the researchers explained. In the first 3 days after illness onset, performing two antigen tests 2 days apart (protocol 3) was more sensitive than doing two tests on consecutive days (protocol 2) and a single test (protocol 1). Protocols 2 and 3 remained more sensitive than protocol 1 throughout the 14 days following illness onset, with the largest differences seen during the first 3 days. Protocol 3 saw the highest peak sensitivity (85 percent) vs protocols 1 and 2 (77 percent and 81 percent, respectively). [JAMA Intern Med 2022;doi:10.1001/jamainternmed.2022.1827]

The sensitivity of home antigen test peaked 4 days after illness onset (77 percent), which improved following a second test 1–2 days later (81–85 percent). “[This] suggests that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1–2 days later,” said the researchers.

This household transmission investigation comprised 225 participants (median age 29 years, 52 percent female, 91 percent symptomatic) from 107 households in San Diego County, California and metropolitan Denver, Colorado. Participants used home antigen tests for 15 days and had at least one nasopharyngeal (NP) swab for RT-PCR, viral culture, and sequencing. A total of 3,044 home antigen tests and 642 NP swabs were contributed.

Almost all participants reported no difficulties collecting nasal swabs (95 percent), and said that they would be more likely to get tested if the antigen tests were available over the counter (96 percent).

The findings however are not representative of the entire US population, as nearly 90 percent of participants had not received a COVID-19 vaccine. “[F]urther studies should better assess the performance of antigen tests in vaccinated persons and those with natural immunity,” said the researchers.

Most patients were symptomatic with mild disease and were household contacts of a known COVID-19 patient. As such, the findings may not be applicable to asymptomatic patients, those with severe disease, and those without a known exposure to SARS-CoV-2.

Also, the findings are limited to the SARS-CoV-2 lineages circulating at the time of study, the most common being Alpha (B.1.1.7; 56 percent), Epsilon (B.1.427/B.1.429; 16 percent), and Gamma (P.1; 4 percent). However, evidence shows that antigen tests do perform well with Omicron variants. [Ann Intern Med 2022;175:682-690]

It should also be noted that daily positivity for the home antigen test dropped at 6** days after illness onset (61 percent), and continued to decline at 11*** days after illness onset (16 percent). Daily positivity for RT-PCR was similarly high at both timepoints (86 percent).

“[Nonetheless,] with the widespread availability, ease of use, and rapid turnaround time, home antigen tests may increase testing in populations with barriers to testing in other settings and facilitate identification and isolation of cases,” said the researchers.