Antigen rapid tests: Moving toward more efficient COVID-19 testing | Multidisciplinary

At the time of writing, there have been 175,306,598 confirmed infections and 3,792,777 deaths attributed to the COVID-19 pandemic globally. [https://covid19.who.int/, accessed 14 June 2021] Real-time reverse transcription polymerase chain reaction (RT-PCR) has been instrumental in detecting the infection and preventing more widespread transmission of the disease.

However, as COVID-19 moves toward becoming an endemic disease, widespread RT-PCR testing may no longer be a feasible and cost-effective option. A combination of different test types will be needed to expand testing capacity for COVID-19 in all settings.

When RT-PCR testing is not feasible

The RT-PCR test is the current gold standard to detect SARS-CoV-2 due to its reliability and accuracy. [https://my.clevelandclinic.org/health/diagnostics/21462-covid-19-and-pcr-testing, accessed 11 June 2021] While it is the recommended diagnostic tool to identify acute SARS-CoV-2 infection, its use is hampered by the need for specialized equipment and a skilled workforce. This technique is also time consuming and costly. [J Clin Virol 2020;133:104659] As such, there is a need for a diagnostic method that can overcome these limitations.

SARS-CoV-2 antigen rapid tests (ARTs) can be incorporated into testing strategies when nucleic acid amplification test methods such as RT-PCR tests are not available, turnaround time is too long to inform clinical decision-making, and for public health measures such as contact tracing.

Faster results, frequent testing with ARTs

The turnaround time for PCR tests is 4–6 hours (or approximately 1 hour in the case of point-of-care testing PCR) as compared with 15–30 minutes with ARTs. [https://www.moh.gov.sg/docs/librariesprovider5/default-document-library/appendix-i47e4ee9f78bc41d0a 14c14d70143467c.pdf, accessed 11 June 2021]

According to infectious diseases specialist Dr Leong Hoe Nam from the Mount Elizabeth Novena Specialist Centre, Singapore, this shorter turnover time is one of the greatest advantages of ARTs.

ARTs are also excellent at detecting infection within the first 5 days of illness, at a time when the virus is most infectious and when the risk of transmission is at its height. At this point, the sensitivity of ARTs is similar to that of PCR tests, though it decreases after 5 days.

Another benefit of ART is that due to the quick turnaround time, repeat testing is possible. For instance, testing every 3–5 days allows for a greater chance of early identification of a patient with SARS-CoV-2 before they transmit the infection to a wider population, said Leong. “In this way, the value of ART approaches that of PCR,” he said.

“We have learnt that the more you test, the greater the likelihood of identifying infected individuals. Once you can identify an infected individual, that person has access to healthcare and treatment and in turn, further spread of the infection can be prevented. This is an excellent way of controlling the epidemic,” Leong added.

ARTs: From clinics to homes

It also does not seem practical to build more resource-intensive PCR laboratories, as opposed to attempting to find more cost-effective testing methods. ARTs can and should be used in the general practice setting as results will be available instantly, said Leong. In the future, instead of testing at clinics or designated areas, testing can be conducted at home, he said. Only once rapid testing is accepted and popularized can we move into the endemic preparation phase.

With several types of ARTs available, how does one go about choosing an ART? The main factors for selecting an ART include sensitivity, price, and ease of use or convenience, said Leong.

The Health Sciences Authority, Singapore, has authorized the use of several ARTs, one of which is the Abbott PanBio^TM COVID-19 Antigen Self-Test. [HSA; https://www.hsa.gov. sg/consumer-safety/articles/details/covid19_ARTselftests, accessed 14 June 2021]

“Personally, I find the PanBio test easy to use,” noted Leong.

ART usability in large-scale events or travel

R0 is the reproductive index, or the average number of people who will catch the disease from a single infected person. For COVID-19, the R0 estimate is 2–3, with each case expected to transmit to two to three other individuals. However, in a potential “super spreader” event such as a concert, one infected case could transmit the infection to 5–10 or more people. During these large-scale events, ARTs may be the preferred testing strategy over others, said Leong.

Evidence of this benefit was shown in a recent trial where 1,047 individuals aged 18–59 years with a negative result following ART just prior to a live, indoor concert in Barcelona, Spain, were randomized to attend the 5-hour concert (with compulsory mask use) or go home. [Lancet Infect Dis 2021;doi:10.1016/S1473-3099(21)00268-1]

Eight days post-concert, the participants underwent nasopharyngeal swab tests which were analysed by ART, RT-PCR, and a transcription-mediated amplification test. Two (<1 percent) individuals who went home had positive ART and PCR results, while none of the attendees had a positive ART or RT-PCR result.

Although there is currently no precedence for pre-flight testing, ART should also become a useful testing strategy prior to travelling, said Leong.

Dispelling misconceptions

In general, ARTs are known to be less accurate than RT-PCR tests, occasionally producing false negative results. [https://www.who.int/images/default-source/wpro/health-topic/covid-19/slide4ab28166601e24e-2aaef2c7aca9501907.jpg, accessed 14 June 2021] However, Leong stressed that false positive rates with ARTs are extremely low at <1 percent. A positive result is most likely indicative of an infection, he pointed out.

RT-PCR testing is the gold standard, so why choose ARTs if they are not the best option? According to Leong, every bit of testing can help prevent transmission which is the end goal.

While ARTs can be uncomfortable, a well-done test by a proficient tester can help reduce any discomfort, he added.

When is PCR or serology testing recommended?

“PCR should be used as a confirmatory test and it would be a great complement to ARTs in clinics and hospitals,” Leong said.

In contrast, serology testing is less helpful as individuals can be infected repeatedly. Quantified antibody tests may be a better alternative with current indications suggesting that higher antibodies equate to better protection. However, the optimal antibody level is yet undetermined. “Perhaps this test could help identify who is at risk, who needs a booster dose of the COVID-19 vaccine, and who is safe,” Leong suggested.

Vaccination + ART: Hand-in-hand

Despite it being vital in reducing COVID-19 transmission, vaccination alone is not going to be the panacea, noted Leong. We must be aware that breakthrough infections may occur due to vaccine failures. As such, ARTs will help prevent widespread transmission by quickly identifying COVID-19 infections so that precautionary measures can be taken.