Despite their best efforts at convincing the population of its safety, there is much discomfort and fear around the nasal swab test. Not only is repeated testing difficult for patients, it is also laborious for medical staff, who are required to wear protective equipment and process the samples using expensive reagents. There needed to be an alternative.
In comes the COVID-19 saliva test: a non-invasive RT-PCR-based alternative offered at half the price but with the same sensitivity as the nasal swab test — whose origins can be traced back to a Filipina scientist working over 13,000 kilometers away.
“We’ve held classes since fall last year and it’s because of this.”
Diana Ranoa, a postdoctoral research fellow at the University of Illinois Urbana-Champaign, is talking from Illinois about their path to securing the safety of in-person classes again through the development of a comprehensive campus COVID surveillance system — one that could be adopted in campuses elsewhere and expanded to the rest of Illinois as well.
It was a three-pronged solution dubbed SHIELD T3: test, tell, and target. Based on an initial assessment, the entire campus population had to be tested at least twice a week. Test results had to be given in 24 hours or less to minimize potential spread of the virus. If a positive case had been identified, they needed to be informed within 30 minutes post-validation of their results. Once informed, they would be housed in a quarantine facility or in their dormitories, where they’d be monitored. Most importantly, all of this needed to be done for free.
To do this, first, they established a diagnostics laboratory on campus and began scaling up to roughly 10,000 tests/per day in preparation for the onsite classes. In targeting delivery of results within 24 hours, SHIELD Illinois, as the system was called, hoped to provide real-time information to control the spread even in pre-symptomatic and asymptomatic carriers.
Prior to the pandemic, Ranoa was primarily focused on cancer research — looking at how synthetic drugs elicited immune responses in mammals such as mice, dogs, and cats in the hopes of translating those results to humans. Ranoa had been accustomed to a scientific routine of close contact: big collaborations, training lab mates in new techniques, long hours filled with experiments, and meetings in small rooms.
However, when the pandemic hit, she used her background in immunology and molecular biology to develop a saliva test that would end the pandemic, at least within their campus.
"We had six weeks," said Ranoa. “The chancellor wanted to announce a plan by mid-June.”
Passing ideas around with her principal investigator Paul Hergenrother, Ranoa was sent into an initial team of four people, all of whom understood the urgency of the request. “For us to get back to our normal lives, we have to test everyone on campus,” says Ranoa. “You can’t just do that with a nasopharyngeal swab because compliance would be an issue.” Apprehensions around swab tests stem, in part, from exaggerated tales of discomfort that are only reinforced by media coverage.
Saliva was the clear specimen of choice. Previous studies had shown that other viruses such as Zika virus could be detected in saliva through direct PCR and ongoing research at other universities had demonstrated that SARS-CoV-2 could be too. The presence of this mountain of evidence gave them the direction and momentum to move forward.
They got to work immediately. They discussed objectives at the beginning of the day, rotated the tasks, and worked beyond normal working hours to come up with replicable results necessary in a good protocol. Direct PCR, which removes the need for an additional RNA extraction step, was the way they wanted to go — as these minimized sample loss, cut time constraints, and decreased costs by eliminating the need for purchasing kits that were expensive and limited in supply.
Their principal investigators expedited several processes associated with research safety and the ethical clearance for the acquisition of clinical samples needed to make sure that the test functioned in patients. On the side of funding, there was no need to write a grant. Ranoa says: “It helped that the university said we could buy anything we needed for this project.”
Describing the pre-print of their protocol (a full draft of the research published online for the benefits of transparency, open data, and communication), “It wasn’t peer-reviewed, I acknowledge that,” Ranoa continues. “But we know the technique works so we put it out there so that whoever sees that paper can do the validation studies themselves.”
Apart from the difficulties bringing the test [to the Philippines], the way the media has discussed the test still worries Ranoa. “They’re comparing it to a rapid antigen test,” says Ranoa. Many antigen tests have been shown to be lacking in sensitivity, with a major antigen test used in the UK being recalled by the U.S. FDA recently.
Starting January 2021, Rako Science — a biotechnology firm in New Zealand — had already adopted the saliva-testing protocol and surveillance system the team had developed and has been using these at international terminals.
However, the process of transferring the technology to the Philippines was a different story.
Philippine adoption via Red Cross
During the latter half of 2020, Senator Dick Gordon contacted Diana Ranoa, just at the peak of her work as the COVID lab’s supervisor. He wanted to see if the technology could be transferred to the Philippines, especially considering the incoming typhoon season when evacuation centers were likely to be filled. The high density in these small spaces provided the perfect opportunity for superspreader events.
Within three weeks of the call with Senator Gordon, doctors from University of the Philippines - Manila got the Institutional Review Board (IRB) approval and had collected over a hundred paired samples for the validation study. However, bottlenecks occurred in early October 2020 while the team waited for approval from the Department of Health (DOH).
“I didn’t feel a sense of urgency.” she says. The DOH required that the validation studies up their sample sizes from a hundred to a thousand patients, even when the initial sample size met existing criteria of U.S. FDA-approved technologies. In compliance with these requests, the costs of these tests were shouldered by the Philippine Red Cross. She says: “It wasn’t a very transparent review process either. We were only allowed into the Zoom meeting if it’s our turn to present.”
After roughly four months of waiting, the saliva test was successfully approved in January 2021 following the urging of President Rodrigo Duterte. In April 2021, saliva-based RT-PCR testing was both validated by the Research Institute of Tropical Medicine (RITM) and was declared covered by PhilHealth. Through the Philippine Red Cross, different malls like SM Supermalls, Ayala Malls, and Robinsons Malls now function as drive-thru testing sites. After scanning a QR code and filling up a form, people can just fill a tube with saliva (making sure they haven’t eaten or smoked in the past 30 minutes), screw the cap on, drop it off at the collection center, and get their results within 48 hours or so.
But apart from the difficulties bringing the test into the country, the way the media has discussed the test still worries Ranoa. “They’re comparing it to a rapid antigen test,” says Ranoa. Many antigen tests have been shown to be lacking in sensitivity, with a major antigen test used in the UK being recalled by the U.S. FDA recently. Sensitivity is important in catching positive cases and as more variants emerge in the population. But Ranoa assures the public that the saliva test is just as sensitive as the gold standard. “They’ve shown that they’re pretty much the same.” In fact, it successfully acquired an Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) late last year.
But Ranoa warns that testing is only a small part of the larger picture.
In mid-August 2020, when school began, their testing facility encountered roadblocks. The mandate of testing the entire population twice a week resulted in over 20,000 tests needing to be processed per day — way above their capacity of 10,000 tests/day. Consequently, their turnaround time suffered.
Epidemiologists and bioinformaticians looked at their data real-time and saw that the hotspots were often undergraduates. The team changed the mandate, adjusting to test undergraduates more frequently and decreasing testing frequency for everyone else. This brought down the number of tests needed and it became easier to deliver results within the allotted time-frame. “You have to combine it with everything else to have a very effective surveillance system.”
The university’s investment in the equipment and training has created a model for restoring campus activity around the U.S. and the world. With the capacity building and infrastructure in place, Ranoa foresees that the same technology and protocols for processing saliva can be used for the diagnosis of other diseases such as cancer. “The university already invested in all of these PCR machines.” says Ranoa. “What are you gonna do with those after COVID?”
In addition to the vaccine rollouts continuing around the world, constant, reliable information, through testing, will be key to developing plans to re-open campuses, and with it, the experiences that have been lost — like onsite graduations and other social gatherings.
“I take the bus from when I go home to work and back,” says Ranoa. “The bus route takes me through the soccer fields, the football fields, the volleyball fields and everytime I see students that are able to get out and play. To be able to see the students enjoy a 'normal life' during the height of the pandemic, that was a very rewarding feeling for me. The saliva test helped make that happen.”
***Erratum: An earlier version of the article erroneously stated that Ranoa is a fellow at University of California Urbana Champaign instead of University of Illinois Urbana Champaign. We apologize for this oversight.