As the global scientific community races to create tests for COVID-19 and end the public-health shutdown, Stanford University is trying to speed up the production of a newly developed antibody test, which was made available to its health care workers last week.
Launched on April 6, the test produces results in two or three days, according to a news release from Stanford University School of Medicine. Stanford Health Care is able to test 500 samples per day and it is hoping to "scale up quickly."
Stanford is one of many institutions, academic and commercial, that are working to develop and scale up COVID-19 tests (the Food and Drug Administration has approved 34 emergency use authorizations for COVID-19 diagnostic tests as of Tuesday, according to the agency). Rutgers University on Tuesday received approval from the FDA for a COVID-19 test based on saliva. And Stanford last month developed its first COVID-19 test, which uses a technique called polymerase chain reaction (PCR) to multiply, amplify and analyze DNA samples extracted through nasal swabs (the virology lab has since doubled its testing capacity from 1,000 to 2,000 tests daily).
Commercial companies such as Abbott Laboratories and Cepheid also have developed PCR tests, for which they received FDA approval.
Stanford's newly unveiled serological test detects two types of antibody molecules: immunoglobulin M (IgM), which helps disable the virus and then vanishes from the bloodstream several weeks later, and immunoglobulin G (IgG), which develops later in the infection process and remains in the body for far longer, providing immunity. Unlike the PCR test, which measures whether someone has the virus, the antibody test also determines whether someone has had COVID-19 in the past.
The serological test that Stanford is providing for its health care workers is different from the test that Stanford researchers administered to thousands of volunteers earlier this month at three sites in different parts of Santa Clara County. That study, which aims to gauge the prevalence of virus infections in the county, is led by Eran Bendavid, an associate professor of medicine at Stanford.
Bendavid said the tests that his project was using came from the Premier Biotech, a Minnesota-based drug testing company. The tests, he said, can return results very quickly.
"The upside of these is that they're very inexpensive and very easy to use and you get results within 15 minutes," Bendavid said. "The downside is that they are maybe somewhat less precise than the laboratory-based tests. For the purposes of what we have done — for trying to get a sense of prevalence of antibodies to coronavirus in our community — they are perfect."
Bendavid said the tests somewhat understate the number of cases, a factor that the team is adjusting for in the research project.
While rapid tests such as the one used in the Bendavid study are suitable for research projects, Stanford believes the new serological test developed by its own pathologists is accurate enough for clinical settings. Dr. Yvonne Maldonado, a Stanford professor of pediatric infectious diseases and health research and policy, said during the April 9 virtual town hall that she believes the negative predictive value of the Stanford test is between 95% and 99%.
"If you get a negative test, you can be 95% to 99% certain that the test is accurate," Maldonado said.
The ability to ramp up accurate testing is widely seen as a necessary precondition for ending the economic shutdown and relaxing social-distancing orders. On Tuesday afternoon, California Gov. Gavin Newsom released a list of six critical indicators for getting out of the stay-at-home order. The first indicator is the "ability to monitor and protect our communities through testing, contact tracing, isolating and supporting those who are positive or exposed."
Dr. Mark Ghaly, the state's Health and Human Services secretary, expressed confidence on Tuesday that testing is ramping up and said the numbers are "encouraging." Though he said he doesn't have a specific target for how many tests should be available before the shelter-at-home order is lifted, Ghaly said that with serological tests now gaining approval, California will be able to test "tens of thousands" of people daily. He also said the state is planning to greatly expand the number of community testing sites, as well the range of people who can request tests.
"We are beginning to move beyond just having tests available for the sickest people within hospitals, for health care workers as well as front line workers … (we're) looking to open a number of sites across the state to have community testing, for those who may be early with their symptoms or may have been exposed to somebody who is either asymptomatic or tested positive," Ghaly said.
The state's COVID-19 Testing Task Force credits Stanford Medicine on its website for launching the first serology test invented in California. But even despite efforts by Stanford and others, testing remains a source of frustration in Santa Clara County, where a total of 15,529 patients have been tested for COVID-19 as of April 13, according to county data, with 1,666 testing positive. It still takes more than two days, on average, to get a result, according to the county.
Both locally and statewide, labs have reported huge backups of tests, though Newsom cited some progress on that front Tuesday, noting that the backlog of tests in California has dropped from 59,500 in the beginning of April to about 13,200 as of April 13. The state has conducted about 215,400 tests as of April 13, with 23,338 people testing positive, according to state data.
In addition to boosting the number of tests, researchers at Stanford are also trying to improve reliability. While commercial tests are being developed around the world, Dr. Thomas Montine, chair of the pathology department at Stanford, described existing tests in the news release as "uncertain and variable."
"We thought this was an urgent medical need, and the usual supply chains were unreliable, so we decided to build our own," Montine said.
According to Stanford Medicine, the university's team had been working on the test since March 22. The team, led by Dr. Scott Boyd, associate professor of pathology, validated the new test using samples from patients who tested positive for the virus through Stanford's initial test, which relies on DNA analysis, and plasma samples that were known to be negative because they were collected more than two years ago.
Montine said in the news release that the university has sufficient inventory to run tests for at least six months, though it is currently limited by a number of robots it has to process the test. He said Stanford aspires to ultimately "provide serological testing to as many people in Northern California as we can."
Lloyd Minor, dean of Stanford University School of Medicine, underscored the importance of the new serological test at the April 9 virtual town hall, calling it "very important in terms of looking at the prevalence of antibodies in the community."
"As we move toward thinking about how to come out of shelter-in-place, it will be very important to determine what proportion of the population has developed an antibody response to the virus," Minor said. "That doesn't necessarily mean that those who have antibodies will be immune, but the presence of the immune response is the first step toward evaluating when it's safe to have more social interaction."
Find comprehensive coverage on the Midpeninsula's response to the new coronavirus by Palo Alto Online, the Mountain View Voice and the Almanac here.