Antigen testing vs PCR: less haste, more speed please

Rapid antigen tests promise fast answers, but hospitals may pay a high price for missed diagnoses and false reassurance

In the fight against respiratory infections, a quick answer isn't always the right one. Rapid antigen tests (RATs) have become popular for their quick results and ease of use. These tests can detect specific proteins, known as antigens, on the surface of a virus, and can provide results within minutes. But, according to a recent review in Microorganisms,¹ this convenience comes at a cost: präzision. And in hospitals, that trade-off can have serious consequences.

Julio Garcia-Rodriguez and colleagues focused their search on SARS-CoV-2, influenza A and B, and RSV – all viruses with the potential to cause serious illnesses and, in the case of SARS-CoV-2 and influenza, high pandemic potential.

A headline statistic from the study was that at low viral loads, RATs show sensitivities below 30%. Or, in real terms, 7 out of 10 infections with low viral loads can be missed. This is an undoubted concern when 20–30% of patients presenting to emergency rooms with respiratory infections have low viral loads.¹

Critical Sensitivity

Detecting early, low-viral-load infections is where RATs underperform and where PCR shines. Viral loads vary with disease stage, vaccination status, sample quality, and viral variants that affect the number and type of antigens presented. Unlike RATs, multi-target PCR can detect multiple parts of the virus’s genetic code, maintaining performance even at low levels common in clinical care.

One large meta-analysis found point-of-care RATs detected SARS-CoV-2 with just 70,6% sensitivity, missing nearly a third of cases.² By contrast, molecular-based point-of-care tests achieved sensitivities of 92,8%.² For influenza, another study showed RATs detected only 54,4% of influenza A and 53,2% of influenza B cases³—barely better than a coin toss for a virus most infectious disease experts rank as a top pandemic risk.

Garcia-Rodriguez et al. cite data showing point-of-care PCR testing (using the GeneXpert® system) hits sensitivities of 97,2% for SARS-CoV-2 and above 95% for influenza A and B and RSV.¹

Ripple Effects

Findings from Garcia-Rodriguez and colleagues lend support to why European guidelines lean heavily on PCR—and not antigen testing—for respiratory infections in primary care settings. Missed infections mean missed treatment windows, poorer patient outcomes, and greater spread. Early identification is crucial to curb transmission, especially in hospitals where only one case can spread to cause a nosocomial cluster.

Beyond clinical risk, low-sensitivity testing can lead to an increased burden of repeat testing. Findings from a study of more than 263.000 patients tested for SARS-CoV-2 and influenza showed that those who initially took an antigen test were over four times more likely to undergo additional testing on the same day compared with those who started with molecular PCR tests.⁴ That’s more time, more staff effort, more equipment, and potential delays in effective care.

In respiratory diagnostics, speed without accuracy risks patient safety, fuels transmission, and squanders resources. For health systems to stand firm against looming pandemic threats, having robust, accurate diagnostic tools readily available is essential. In the fight against respiratory infections, a fast answer means little if it’s the wrong one.