Antigen rapid test vs RT-PCR for COVID-19: What you need to know

While RT-PCR* is the current gold standard to confirm a SARS-CoV-2 infection, antigen rapid test (ART) for COVID-19 allows for quick detection of SARS-CoV-2 and thus fast triaging of infected patients requiring isolation at the population level, according to studies presented at ECCMID 2021.  

“[RT-PCR does not have a] fast enough turnaround time and [places] high demands on personnel, equipment, and consumables. Therefore, its use for the purpose of population-wide testing is limited,” researchers said.  

“[On the other hand,] antigen-based detection is inexpensive, rapid, and easy to use,” they pointed out. ART can provide results in approximately 15 minutes, which is faster and at a lower cost than the standard RT-PCR.

ART also presents a point-of-care testing, without the need for specialised equipment or personnel, which according to the researchers, is useful “in situations with limited access to molecular methods or no staff expertise.”

Population screening: ART as a complement to RT-PCR

As early and reliable detection of new COVID-19 cases is crucial to containing the spread of the virus, researchers compared the utility of ART vs RT-PCR in the context of population-wide screening involving 11,142 individuals (age ranging from 7 months to 98 years) who attended a hospital collection site for preventive testing in Czech Republic. [ECCMID 2021, abstract 1391]

A total of 13,130 nasopharyngeal swab samples were subjected to the Panbio COVID-19 Ag Rapid Test on-site. Those who tested negative on the ART but reported COVID-19-related symptoms, such as fever, loss of smell or taste, sneezing, nausea or vomiting had additional samples collected for further testing with RT-PCR.

Overall, 679 people tested positive on the ART — of which 401 showed symptoms of COVID-19 (representing the true positive population for ART) and the remaining were asymptomatic. 

Among the 12,451 individuals who tested negative on the ART, 1,423 people had reported symptoms and thus subjected to further testing by RT-PCR. A total of 259 turned out to be positive based on the RT-PCR test, representing the false negative population.

Combining these data yields a sensitivity rate of 60.8 percent for antigen testing in symptomatic persons.

“To minimize the risk of false-negative results, strategies based on the combination of antigen and PCR testing or repeated antigen testing with high enough frequency are advised,” said the researchers.

Rapid triaging

“Despite a lower sensitivity to detect infection [compared with RT-PCR], ART can be an important tool for screening because of quick turnaround time, lower costs and resource needs, high specificity, and high positive predictive value (PPV) in settings of high pretest probability,” pointed out another group of researchers led by Dr Charalampos Zarras from Hippokrateion Hospital of Thessaloniki in Thessaloniki, Greece.

The researchers compared the Panbio ART against RT-PCR in 195 symptomatic patients who presented to the emergency department in a hospital.

“It is important that the fastest time from screening to reporting results can accelerate the isolation of infectious individuals and is especially important in an area with high prevalence,” highlighted Zarras and colleagues.

A total of 113 samples turned out to be positive based on RT-PCT testing, of which 57 were also initially detected as positive by the ART. This yields a sensitivity rate of 50.4 percent. [ECCMID 2021, abstract 530]

As all the 57 samples tested positive on ART were validated to also be true positive by RT-PCR testing — this corresponds to a PPV of 100 percent. Specificity was 100 percent.

Another 56 samples which initially tested negative on the ART eventually turned out to be positive by RT-PCR (ie, false negative for ART).

“RT-PCR should be performed to confirm a negative antigen test result,” said Zarras and co-authors.

Of note, the 57 true positive samples showed RT-PCR mean cycle threshold (Ct) value that was lower than the ART false negative samples (ranging from 16.8–17.1 vs 26.5–26.9 for the S, N, and ORF1ab genes tested). This indicates that ART performs better for samples with high viral load (reflected by lower Ct values), for instance during the acute phase of COVID-19.

High impact within 1^st week of illness

When tested  within 7 days of symptom onset — a  period when patients are likely to have a high viral load, ART in general can reach a high sensitivity rate of >90 percent, according to Dr Claudia Denkinger of Heidelberg University Hospital, Heidelberg, Germany, who spoke during a session on ART for COVID-19. [ECCMID 2021, 9^th Jul Integrated Sessions]

As patients with a high viral load are more infectious (ie, transmission-relevant) than those with a low viral load, ART presents a valuable tool that allows for large screening programme to contain transmission.

The key thing about ART is it is “fast” and you don’t have to wait for days from PCR results to know who has been infected and should isolate themselves, said Denkinger.

However, tested at any point of infection, the sensitivity of ART in general is about 40–50 percent, she pointed out. “Hence, this cannot be a rule-out test … and this is especially critical for asymptomatic [cases] because we don't know when the exposure happened or when the onset of infection was, so we might be testing at any time at any point of the infection [beyond the first week.]”

Explaining how ART supports public health interventions overall, Denkinger said testing is not sufficient on its own and should be used in combination with other containment and mitigation measures to control the spread of the disease.

ART is useful to increase the capacity of testing and particularly, to identify those that are transmission-relevant and to inform population-wide distancing measures, she explained.

What to do with ART results? 

Individuals who have a positive result from ART should get a confirmatory PCR test immediately and isolate themselves until they tested negative on PCR, according to guidance from the Singapore Health Ministry.

Meanwhile, those with negative ART test should continue to be vigilant and observe the prevailing precautionary measures.

 

   

*RT-PCR: Reverse transcription polymerase chain reaction