Read our COVID-19 research and news.

A woman spits into a tube so that her saliva can be tested for the presence of the novel coronavirus.

University of Illinois, Urbana-Champaign

New drool-based tests are replacing the dreaded coronavirus nasal swab

Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

First, a technician pushes a pencil-length swab to the very back of your nasal passages. Then you pay $100 or more, and wait days for an answer. But faster, cheaper, more pleasant ways to test for the novel coronavirus are coming online. This month, the U.S. Food and Drug Administration granted emergency use authorization for two tests that sample saliva instead of nasal fluid, and more innovations are likely after FDA relaxed rules to allow new tests to be adopted more quickly. One candidate was announced last week: an experimental test, potentially faster and cheaper, that analyzes saliva in a new way.

“There is real promise here,” says Anne Wyllie, a microbiologist at Yale University who helped develop one of the new tests authorized this month. Takanori Teshima, chief of laboratory medicine at Hokkaido University, who also reported successful results testing saliva, agrees. “It will have a big impact worldwide.”

When SARS-CoV-2, the respiratory virus that causes COVID-19, emerged in December 2019, researchers scrambled to develop tests to detect the virus. Initially, they turned to a long-trusted technique for diagnosing respiratory infections: looking for viral genetic material in mucosal fluid, thought to be the best hunting ground for a respiratory virus, collected from deep in a patient’s nasal passages. That’s where the 15-centimeter swab comes in. The swab goes into a plastic tube with a chemical mixture that stabilizes the virus during transport to a diagnostics lab. There, technicians extract its genetic material and load it into a machine to carry out the polymerase chain reaction (PCR), which amplifies snippets of genetic material unique to the virus.

The procedure accurately identifies infections about 95% of the time. But the test is uncomfortable and, because collecting the swab requires close contact with patients, it puts medical personnel at risk of contracting the virus. “Nobody wants to do that job,” Teshima says.

Testing saliva for SARS-CoV-2 was no sure thing. Studies with other respiratory diseases showed saliva tests identified only about 90% of people for whom swab tests indicated an infection. But the appeal of an easier and safer test for the new coronavirus led researchers to try. People being tested simply drool into a bar-coded plastic tube, seal it, and drop it in a pouch that’s shipped to a lab for PCR analysis. Because the procedure directly tests the fluid responsible for transmitting the virus between people, it may give a better indication of who is most contagious, says Paul Hergenrother, a chemist at the University of Illinois, Urbana-Champaign (UIUC), who led his university’s saliva test development.

As early as 12 February, researchers in Hong Kong and China reported in Clinical Infectious Diseases that they could identify SARS-CoV-2 from saliva in 11 of 12 patients whose swabs showed virus. Since then, groups in the United States, Singapore, and Japan have confirmed and further simplified the procedures, cutting out costly steps such as adding specialized reagents to stabilize the virus during transport and extract the genetic material.

In May, Wyllie and Yale colleagues teamed up with the National Basketball Association, which provided $500,000 to develop Yale’s saliva test; the test is now used for frequently testing players. On 4 August, the Yale team posted a preprint on medRxiv that said its saliva test agreed with swab results 94% of the time, at a cost of as little as $1.29 per sample, roughly 1/100 as much as commercial swab-based tests. On 15 August, FDA granted emergency approval for the SalivaDirect test, so that other FDA-approved labs can use the protocol. Last week, the agency extended approval to the UIUC test given its similarity to the Yale test. UIUC is now using its saliva test to test all 60,000 students, faculty, and staff twice a week, so they can isolate infected individuals as quickly as possible. “Testing saliva makes sense scientifically, and it makes sense logistically,” Hergenrother says.

new saliva test for RNA viruses, such as Zika and SARS-CoV-2, was reported last week in Science Advances by researchers at the University at Albany. It could be even faster and cheaper because it does not need expensive lab equipment such as PCR machines. Rather than amplifying RNA to identify the virus, the approach uses snippets of DNA that bind to short, unique sections of RNA and change them from linear strands to loops. That alters how the RNA behaves in a common lab procedure known as gel electrophoresis, making it easy to detect. “This is innovative,” Wyllie says.

A relaxation of FDA rules announced last week could lead to still more variants. The new rules allow approved clinical labs to use tests they have developed without any additional approval step. In a tweet, Michael Mina, an epidemiologist at Harvard University’s T.H. Chan School of Public Health, called FDA’s decision “Huge news!!” because it would encourage labs to develop novel tests. It may also help speed development of rapid tests that look for viral proteins rather than genetic material—an efficient way to screen large numbers of asymptomatic people.

“We don’t need one test to be the end all and be all,” Wyllie says. “We just want options.”