Are We Testing for Omicron Wrong?

If confirmed in follow-up research and if the diagnostics industry can pivot quickly enough, findings from a South African study could make COVID-19 testing a lot easier for patients and healthcare workers, as the SARS-CoV-2 Omicron variant becomes the dominant source of infection.

In a manuscript posted to the medRxiv preprint server on Friday, researchers from the University of Cape Town reported that saliva samples yielded more accurate results in PCR analyses when Omicron was involved compared with those collected via nasal swabs.

When patients carried the Delta variant, on the other hand, nasal swabs were more accurate, according to the group, led by Diana Hardie, MBChB, MMedPath, who also heads the diagnostic virology laboratory at Groote Schuur Hospital.

The findings came from an analysis of 382 patients tested at Groote Schuur from August through this month, with viral whole-genome sequencing performed on isolates from those with positive results. Just over 300 were tested prior to Omicron's emergence, with 31 testing positive for the Delta variant. Another 74 arrived at the hospital after Omicron became common, of whom 36 were positive for that variant.

All patients had both saliva and mid-turbinate nasal samples taken for RT-PCR analysis. The "gold standard" for positivity in the study was detection of SARS-CoV-2 RNA with either swab.

For the Delta variant, the positive percent agreement for each sampling method, in comparison with this "gold standard," was 71% for saliva and 100% for the nasal swabs. But this was reversed for Omicron, with 100% agreement between saliva samples and the gold standard, but only 86% for nasal swabs.

Nasal swabs have been the standard for COVID-19 screening and diagnosis ever since the virus was discovered, but that may no longer be appropriate in an Omicron-dominated pandemic landscape, the authors concluded.

"These findings suggest that the pattern of viral shedding during the course of infection is altered for Omicron with higher viral shedding in saliva relative to nasal samples resulting in improved diagnostic performance of saliva swabs," Hardie and colleagues wrote.

They noted, as have others, that Omicron is distinguished by "more than 50 distinct mutations." These seem to have resulted in increased infectivity, but they could also affect other aspects of the virus's behavior, including the tissues it may prefer to infect.

With that in mind, Hardie's group pointed to a recent lab study from Hong Kong (as yet unpublished but highlighted in a press release) indicating that Omicron is less likely to lodge in the lung compared with earlier variants. This not only suggests that Omicron is less lethal, but also that the many mutations confer "altered tissue tropism."

However, while saliva sampling may be easier to perform than nasal swabbing, the researchers noted that it's not as simple as spitting in a cup. At Groote Schuur, patients were instructed to swab the inside of the mouth -- both cheeks, above and below the tongue, the gums, and hard palate -- for a total of at least 30 seconds. They were also told not to eat, drink, smoke, or chew anything for at least 30 minutes beforehand.

Another point to consider is that, in the U.S. and most other countries, testing has been predicated primarily on nasal swabs. Although some saliva-based tests have been authorized and are commercially available, the vast majority of currently accessible kits for healthcare use and for at-home self-testing rely on nasal swabs. It would likely take months to retool the supply chain to prioritize saliva sampling -- by which time Omicron may have been supplanted by another variant with its own unique characteristics.

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