For coronavirus tests, the nose may not be the best place

Over the past two years, diagnosing a coronavirus infection has often required probing the nose. Healthcare professionals insert thin cotton swabs deep into people’s nasal cavities, while home tests ask us to master the shallow turn in both nostrils.

“The traditional approach to diagnosing respiratory infections has been through the nose,” said Dr. Donald Milton, an expert on respiratory viruses at the University of Maryland.

But the rapid spread of the omicron variant and questions about the sensitivity of home tests have reignited an argument over whether the best way to detect the virus would be to take the sample somewhere else: the mouth.

“The virus appears first in the mouth and throat,” Milton said. “That means the approach we’re taking to testing has issues.”

Taking saliva samples or rubbing the inside of the mouth can help identify people infected with the virus days earlier than nasal rods, some research suggests.

The science is still evolving, and the data paint a complex picture, suggesting that saliva-based tests have their limitations. Many laboratories are not currently equipped to process saliva, nor are the home antigen tests available in the United States authorized to do so.

But even saliva skeptics recognize that oral samples have some unique advantages. And with the micron on the march, some experts say testing companies, labs and federal officials must work more urgently to determine the best locations and sample types for the virus.

“We need to be adaptable,” said Anne Wyllie, a microbiologist at the Yale School of Public Health, who is one of the developers of SalivaDirect, a non-commercial polymerase chain reaction (or PCR) testing protocol. “I see so many labs or governments that are fixated on a certain type of sample or test that, even with changing data or testing preferences, they don’t make the necessary adaptations in their testing programs.”

The saliva thesis

Scientists began investigating saliva tests in the early months of the pandemic. They were eager to find a method that was more comfortable than the deep nasopharyngeal sticks that were the standard at the time and that didn’t require trained healthcare professionals or the nasal sticks, both of which were in short supply. With saliva, people could simply spit it into a tube and hand it over for processing.

Some lab professionals were skeptical that the saliva test would be a reliable way to detect the infection.

“Initially there were concerns that saliva was not the gold standard sample, that it was not the most sensitive sample,” said Glen Hansen of the Clinical Microbiology and Molecular Diagnostics Laboratory at Hennepin County Medical Center in Minnesota.

But in the fall of 2020 dozens of studies suggested that saliva was a suitable sample for testing.

“There has been a growing body of evidence that, at the very least, saliva works well — it’s as good as, or better, when collected and processed properly,” Wyllie said.

Evidence also emerged that the virus tended to appear in saliva before accumulating in the nose, suggesting that saliva samples could be the best way to detect infection early.

Milton and his colleagues recently found that in the three days before symptoms appeared and for the next two days, saliva samples contained about three times more virus than nasal samples and were 12 times more likely to produce a positive result. PCR After that, however, the viruses began to accumulate more in the nose, according to the study, which has not yet been published in a scientific journal.

The Food and Drug Administration (FDA) has already authorized several saliva-based PCR tests, which have proven popular for screening students in schools.

“Saliva has really become a valuable specimen type and one that has been increasingly advocated as a basic specimen for testing,” Hansen said.

The advantages of saliva can be accentuated with the omicron, which appears to replicate more rapidly in the upper respiratory tract and has a shorter incubation period than previous variants.

Any testing method that can reliably detect the virus earlier is particularly valuable, experts said.

The complications

Saliva also has negative sides. Although the virus appears to accumulate in saliva early on, the nose may be a better place to detect it later in the course of the infection.

Researchers at the California Institute of Technology found that while the virus usually reaches saliva first, it eventually rises to higher levels in the nose. Their results suggest that highly sensitive tests, such as PCR, can detect infections in saliva days earlier than with nasal rods, but less sensitive tests, such as antigen tests, cannot.

The data on saliva is still mixed, some experts note.

“There are these few studies that I found really interesting,” said Dr. Mary K. Hayden, an infectious disease physician and clinical microbiologist at Rush University Medical Center in Chicago.

But Hayden said he was interpreting the new studies with caution because “for years and years” research has suggested that nasopharyngeal samples are better at detecting respiratory viruses.

Some scientists also have practical concerns. The mouth is “a slightly more uncontrolled environment compared to the nasal passages,” said Joseph DeRisi, a biochemist at the University of California at San Francisco who is president of the Chan Zuckerberg Biohub and author of the paper on the cheek stick. “Did you drink a soda just before taking the test? The pH will be different. And those things matter.”

Saliva can be “sticky and difficult to work with,” especially when patients are sick and dehydrated, Marie-Louise Landry, director of the clinical virology laboratory at Yale New Haven Hospital, said in an email.

Ultimately, different approaches may be needed in different circumstances. For people who have had symptoms for several days, nasal sticks may be a good option, while saliva may be better suited for large-scale screening of asymptomatic people, suggested Hansen. “We need to put the right test in the right places,” he said.

In Britain, some home tests require swabbing swabs in both the throat and nose, an approach that may be worthwhile, experts said.

“Sampling from multiple places will always give you an advantage,” Hayden said.

But if test makers want to add saliva samples or throat swabs, they will need to validate their tests with those samples and submit the data to regulatory bodies. At a US Senate hearing Tuesday, FDA commissioner Dr Janet Woodcock noted that manufacturers may also have to reconfigure their tests to accommodate larger swabs that are designed for the throat.

It remains unclear whether any of the major home testing companies have plans to do so.

“We continue to monitor and evaluate,” said John M. Koval, a spokesman for Abbott Laboratories, which does rapid antigen testing. “Our test is currently indicated for nasal use only.”

_{Translated by Luiz Roberto M. Gonçalves}