For coronavirus testing, the nose may not always be best

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

But the rapid spread
of the omicron variant, and questions about the sensitivity of at-home tests,
have rekindled a debate over whether the best way to detect the virus is to
sample a different site: the mouth.

“The virus shows up
first in your mouth and throat,” Milton said. “That means that the approach
we’re taking to testing has problems.”

Collecting samples of
saliva, or swabbing the inside of the mouth, could help identify people who are
infected with the virus days earlier than nasal swabs do, some research

The science is still
evolving, and the data paint a complex picture, suggesting that saliva-based
tests have limitations of their own. Many labs are not currently set up to
process saliva, nor are the at-home antigen tests available in the United
States authorised for it.

But even the saliva
sceptics acknowledge that oral specimens have some unique advantages. And with
omicron on the march, some experts say that testing companies, labs and federal
officials should be working more urgently to determine the best sample sites
and 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 noncommercial
polymerase chain reaction (or PCR) testing protocol. “I see so many either labs
or governments who are so fixated on a certain sample type or a certain test that
even with changing data or test preferences, they don’t make the necessary
adaptations to their testing programs.”


Scientists began
investigating saliva testing in the early months of the pandemic. They were
eager to find a testing method that would be more comfortable than the deep
nasopharyngeal swabs that were the standard at the time and that would not
require trained health care workers or nasal swabs, both of which were in short
supply. With saliva, people could simply spit into a tube and hand it over for

Some laboratory
professionals were sceptical that saliva testing would be a reliable way to
detect infection.

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“There were concerns
initially that saliva was not the gold standard sample, that it wasn’t the most
sensitive sample,” said Glen Hansen of the clinical microbiology and molecular
diagnostics laboratory at Hennepin County Medical Center in Minnesota.

But by fall 2020,
dozens of studies had suggested that saliva was a suitable sample for testing.

“There’s been a
growing body of evidence that at the very least, saliva performs well — it’s as
good as, if not better, when it’s collected properly, when it’s processed
properly,” Wyllie said.

Evidence also emerged
that the virus tended to appear in saliva before it built up in the nose,
suggesting that saliva samples might be the best way to detect infections

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

The Food and Drug
Administration has now authorised numerous saliva-based PCR tests, which have
proved popular for screening students in schools.

“Saliva really has
turned out to be a valuable specimen type and one that has increasingly been
advocated as a primary testing sample,” Hansen said.

Saliva’s advantages
may be more pronounced with omicron, which appears to replicate more quickly in
the upper respiratory tract and have a shorter incubation period than earlier
variants. Any testing method that can reliably detect the virus earlier is
particularly valuable, experts said.

“I think omicron has
really changed the testing game because of how quickly the virus replicates and
how quickly it spreads,” said Dr Robby Sikka, who chairs the COVID-19 Sports
and Society Working Group and who helped bring saliva testing to the NBA in
2020. (Both Sikka and Wyllie serve as unpaid board members for SalivaDirect.)

Some experts have
also theorised that omicron may be better at replicating in the cells of the
mouth and throat than other variants have been.

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A team of South
African researchers recently found that while nasal swabs performed better than
saliva swabs when detecting the delta variant, the opposite was true for
omicron. (The study, which used PCR tests, has not yet been reviewed by

More research is
needed, and another small new study, conducted at a San Francisco testing site
during an omicron surge, was less encouraging. Of the 22 people who tested
positive on a rapid antigen test using standard nasal swabs, only two tested
positive when their inner cheeks were swabbed. The scientists are currently
studying whether throat swabs perform better.


Saliva also has
trade-offs. While the virus appears to build up in saliva early, the nose may
be a better place to detect it later in the course of infection.

Researchers at the
California Institute of Technology found that while the virus often spiked
first in saliva, it ultimately rose to higher levels in the nose. Their results
suggest that highly sensitive tests, like PCR tests, may be able to pick up
infections in saliva days earlier than they do in nasal swabs, but that
less-sensitive tests, like antigen tests, might not.

The data on saliva
are still mixed, some experts noted.

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

But Hayden said she
was interpreting the new studies cautiously because “for years and years and
years,” research has suggested that nasopharyngeal specimens are best for
detecting respiratory viruses.

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

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

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Ultimately, different
approaches may be required in different circumstances. For people who have had
symptoms for several days, nasal swabs might be a good choice, while saliva
might be best suited for the large-scale surveillance screening of asymptomatic
people, Hansen suggested. “We need to get the right test into the right
places,” he said.

In Britain, some
at-home tests require swabbing both the throat and the nose, an approach that
may be worth pursuing, experts said.

“Sampling multiple
sites is always going to give you an edge,” Hayden said.

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

It is not yet clear
whether any of the major at-home testing companies have plans to do so. “We
continue to monitor and evaluate,” said John M Koval, a spokesperson for Abbott
Laboratories, which makes rapid antigen tests. “Our test is currently indicated
for nasal use only.”

Even scientists who
were convinced of saliva’s potential were reluctant to recommend that people
swab their mouths or throats with tests that are not authorised for that
purpose. (The FDA has also warned against this.) The biochemistry of the mouth
is different from that of the nose and may affect the test results, potentially
yielding false positives, scientists said.

“It’s not as easy as
just saying, ‘Hey, just use a rapid antigen for saliva,’ ” Hansen said.

But experts said they
hoped that laboratories, test manufacturers and regulators would move swiftly
to evaluate whether any currently available tests might perform better on other
sample types.

Ultimately, the
country will be well-served by having a wide variety of testing options and the
ability to switch between them as circumstances warrant, scientists said.

“For future
pandemics, and even maybe as omicron evolves,” Hayden said, “we need
flexibility in our testing systems.”

© 2022 The New York
Times Company

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