Goal Is to Develop New Reagents, Tests, Vaccines and Treatments
By Andy Fell
Clinical pathologists, infectious disease physicians and scientists at the UC Davis Medical Center, California National Primate Research Center and Center for Immunology and Infectious Diseases are collaborating on new reagents, diagnostic tests and a vaccine for the COVID-19 coronavirus. Their goal is to unravel the biology and infectious pathology of this new virus, and to develop means for prevention and ultimately treatment.
The team began by isolating, characterizing and culturing coronavirus from a patient treated at UC Davis, the first community-acquired case in the U.S., with the goal of making diagnostic tests in-house. These tests will make use of UC Davis’ existing infrastructure for high-capacity clinical laboratory testing. Widespread testing is crucial to unravel the true prevalence, lethality and contagiousness of COVID-19. Genetic differences between the UC Davis coronavirus isolate and those from other countries or parts of the U.S. may give clues about how the virus has spread.
Culturing the virus in the laboratory will allow researchers to investigate the basic biology of coronavirus — how it attacks and invades cells, and what treatments might work against it.
The UC Davis researchers were able to quickly launch their coronavirus research program because of the existing strong relationships between the School of Medicine, the CIID and the primate center, where researchers study HIV/AIDS, Zika and other infectious diseases.
“We knew who to call when the time came — it was our colleagues and partners at the CIID and CNPRC,” said Nam Tran, associate professor of pathology and laboratory medicine and senior director of clinical pathology, in charge of the SARS-CoV-2 testing at UC Davis Health. The UC Davis Clinical Laboratory will be deploying such tests soon, while at the same time developing high-throughput assays to meet the growing demand in the community. The high-throughput tests can perform up to 1,400 tests per day. Collaboration with the CIID and primate center is crucial to accelerate test 
validation required by the United States Food and Drug Administration, Tran said.
Nonhuman primate model
The UC Davis researchers also plan to develop a model of coronavirus infection in nonhuman primates. Researchers in China have already shown that COVID-19 will infect rhesus macaques, said Chris Miller, an infectious disease scientist at the primate center and professor of pathology, microbiology and immunology at the UC Davis School of Veterinary Medicine and CIID. This animal model could be used to develop and test potential treatments and vaccines, Miller said.
Among other objectives, the researchers plan to use the nonhuman primate model to look at how age influences the course of COVID-19 disease. So far, it appears that the infection is generally mild in children and younger people and most serious in people over 60, but it is not clear why.
Nonhuman primates are a uniquely powerful model for investigating human disease, said Professor John Morrison, director of the primate center. The coronavirus pandemic shows the need for significant investment in the national primate research centers so that they can build collaborations and be ready for such outbreaks, he said.
Teamwork essential
All work with coronaviruses has to be conducted in biosafety level 3 (BSL3) facilities, requiring special precautions. The investigators obtained regulatory approvals from the institutional ethical and biosafety committees, a complex and sometimes lengthy procedure.
“Given the clinical significance and global importance of these projects, emergency committee meetings were called and experts worked over time to assure safety and full compliance with CDC guidelines and all regulatory requirements in a record turnaround time,” said Angela Haczku, associate dean for translational research at the UC Davis School of Medicine.
The researchers have applied for supplemental grant funding from the NIH to support their work. But they are not waiting for federal funds to be awarded. UC Davis is using internal campus and primate center funds to get the work underway.
Originally published in the UC Davis news…
What happens if you mix the samples from five people and run that through the test?
Would the test end up randomly testing just one of them?
Or would the test return positive as long as it finds the virus in the mixture?
The answer is behind door # 3. Question #1 is theoretic, unimportant. Given #1, question #2’s answer is false.
If the samples are mixed, though, you’d have to assume a “presumptive yes” on all 5 and quarantine them all if there is a positive result. Hoping that #1 is never done… too little info, too much impact… IMO…
Focusing only on #3:
If the test would return a positive from a mixture, and you want more details, you could run the test for the individuals (not a mixture). If a negative result is reliable, then running it once would clear five people instead of running five tests.
Suppose there are 8 people and 1 is infected. The test would go like this:
1) divide the 8 people into 2 groups of 4 each. Test result: Group A is positive, Group B is negative.
2) divide Group A into A1 and A2 of 2 people each. Test result: A1 is positive, A2 is negative.
3) test one of the persons (A11, and A12) in group A1. Test result: A11 positive means A11 is infected. A11 negative means the other person A12 is infected.
4) If A11 was positive, you need to test A12 also, because they could both be infected.
Together the test was only run 3.5 times but tested 8 people, and identified the single person who was infected.
I explained it wrong.
1) divide the 8 people into 2 groups of 4 each. Test both. Result: Group A is positive, Group B is negative. -> 2 tests
2) divide Group A into A1 and A2 of 2 people each. Test only A1. Result: Negative (meaning someone in A2 is infected) -> 1 test
3) Test the first person in A2. If the result is negative, then the other person is infected. -> 1 test.
Total 4 tests ran for 8 people.
But this way of testing doesn’t save anything unless very few people are infected. It might still be useful to survey how many households are infected or similar.
This ridiculous exercise is more suited to a philosophy course than scientific method.