Skip to main content
Premium Trial:

Request an Annual Quote

Mount Sinai Leveraging T-Cell-Based Technology to Determine Immune Response to SARS-CoV-2


NEW YORK – An international and multidisciplinary team led by researchers from Mount Sinai has developed a test to measure the functionality of a patient's T cells, which can indicate their immunity to SARS-CoV-2. 

To date, most tests that have been developed to determine a patient's immune status for SARS-CoV-2 have been antibody based. However, there is much skepticism about the clinical use of such serology-based tests.

Ernesto Guccione, an associate professor of oncological sciences at Mount Sinai's Icahn School of Medicine, who helped lead the development of the test with partners from Duke-NUS Medical School in Singapore, said that one of the downsides of using antibodies to determine immunity is that they are short-lived — antibodies against SARS-CoV-2 may be present in a person's blood only for a few months.

He added that antibodies are easy to quantify and are useful to protect from infection, but once the SARS-CoV-2 virus makes it past the antibodies, T cells are the key line of defense to protect from severe disease.

The researchers began developing the test because there are "no easy ways to quantify the functionality of T cells" to see how well they're protecting a patient from severe disease, Guccione said. But by using a proxy to quantify the functionality of T cells that were present in a patient's blood, they created a method to assess that person's immune status. Guccione and his colleagues describe their method in a paper published last week in Nature Biotechnology that compiled data on the test across multiple cohorts.

The test they developed, called qTACT, relies on quantifying CXCL10 messenger RNA. CXCL10 is a chemokine that, when expressed, linearly correlates with the activation of T cells. When a patient is exposed to SARS-CoV-2 antigens, the T cells release interferon gamma, which stimulates monocytes in the blood to produce CXCL10. Measuring the expression of CXCL10 can then be used to quantify immunity. The researchers determined the CXCL10 gene produced the most accurate results through sequencing the whole-blood samples of both patients who had recovered from COVID-19 and patients who had been vaccinated and then by identifying "the gene that was the most correlating and could act as a proxy for the presence of antigen-specific T cells," Guccione said.

When running the test, the sample is incubated with synthetic peptides that cover different proteins of the SARS-CoV-2 virus and left overnight, then run through a qPCR machine with a two-color system: one normalizer and one primer and probe set for CXCL10. Traditionally, T-cell tests have utilized flow cytometry or ELISpot methods, which look at protein production rather than RNA, so the researchers had to tweak the buffers and dilution used in the test to remove PCR inhibitors and adapt it for qPCR, Guccione said.

"We're not directly measuring the T cells, we're using a trick," he said. "We're measuring an internal amplification."

He added that, while the test could be run in six hours instead of 24, the assay is intended for "more long-term" use, where turnaround time matters less and there's "no urgency," such as for immunocompromised patients who are looking to figure out how protected they are. The team used 24 hours for the Nature study because it was easier to collect large numbers of samples and run them all at the same time — it was a "choice of practicality," Guccione said. 

The limitations of the test include the longer processing time, the need to purify RNA, the moderate price, and the necessity of a medium level of technical skill, the researchers wrote in the paper. However, the team developed another assay using the same method, called the dqTACT assay, that eliminates the sample preparation and lowers the processing time, cost, and skill required.

The team is also using their method to develop assays for measuring T-cell response to different SARS-CoV-2 variants, as well as determining how the T-cell test could be used in clinical applications, Guccione said.

On the commercial front, both tests have been exclusively licensed by Hyris, a UK-based diagnostic company that will be commercializing and distributing it.

Stefano Lo Priore, Hyris' managing director, said that the company is "always on the lookout" for new technologies and that the Mount Sinai test "hits many of the sweet spots" the firm is interested in. It provides "an opportunity to radically simplify the traditional T-cell test" and replace it with PCR, which makes it "very attractive in terms of the mechanics of the test," since it is simpler to use than other methods.

One of those methods, used by Adaptive Biotechnologies in its T-Detect COVID test, which received Emergency Use Authorization from the US Food and Drug Administration last year, is sequencing — a method that Guccione called costly and labor-intensive.

Adaptive's Senior Director of Corporate Communications Laura Cooper noted via email that "there is clearly a large, unmet need to better understand cellular immunity to SARS-CoV-2, particularly in underserved populations, and we’re glad to see more innovation in this space." She added that its "[T-cell receptor] sequencing technology for quantitative, high-throughput measurement of cellular immunity is one of the few technologies that can be done at scale, using DNA extracted from whole blood."

Adaptive's test is the only T-cell based assay authorized by the FDA to determine an individual's immune response to SARS-CoV-2.

"Notably, TCR sequencing is one of the few approaches that can address the important questions about cellular immunity in COVID-19 at scale without needing live cells (no need for special handling) which is a factor for many technologies, including the assay being developed by Hyris," Cooper said.

Lo Priore said that the test is being offered for research use in Singapore thanks to the company's existing presence there, and it intends to seek regulatory approval for the assay in Canada as well. The test received CE marking about a month ago. New standards for CE marking went into effect at the end of May under Europe's In Vitro Diagnostic Regulation rules, which are more stringent than previous regulations that governed CE marking. Lo Priore said that the company already conformed as much as possible to the new rules and at some point plans to submit future test upgrades or improvements to a notified body for certification.

Hyris is also reviewing materials for a submission to the US Food and Drug Administration for Emergency Use Authorization, Lo Priore said, and is looking at Southeast Asia and China as other possible markets. Clinical trials of the test have been completed in Europe, and the firm is planning US-based clinical trials. The "main goal" is to "make sure everything works very well," and the company has planned conversations with clinicians to help figure out how the assay could best be used in clinical applications, he said.

There is an "obvious use" for the test in the development of vaccines, where it could be used to evaluate the effects of a vaccine over time, as well as by health authorities to supplement booster management and help determine whether a new booster is needed. In segments of the population that require extra care, such as oncological, pre-operative, or transplant patients, the test could be utilized to gauge immune status and protection from the virus, Lo Priore said.

Guccione echoed these thoughts, saying that although the assay could be used by anyone who wants to know their immunity status, he sees it being used for immunocompromised patients or for people who want to know their vaccine response.

While Hyris hasn't come up with a price for the test just yet, Lo Priore said the firm intends to make it affordable to the general population. It could be sold either as an individual test or in combination with the Hyris System, which includes a miniature multiplex PCR instrument and associated software. The system costs about $5,000 in North America, although the price varies based on the software configuration used. To date, Hyris has sold several hundred of its systems and has "several thousands of users."

Lo Priore said he views the T-cell test as the first in a "family" of tests for a variety of diseases, but the immediate next step is engaging clinical practitioners to see where the assay could best be utilized and "fine-tune the real-world application."

It's a "very flexible tool" that "could be used in many ways," he said.