When COVID-19 spread across the U.S. in early March, Mayo Clinic’s Advanced Diagnostic Laboratory (ADL) urgently responded. Lab spaces were transitioned, staff reassigned and funding approvals were fast-tracked. Its goals were to accelerate research, development, translation and implementation of novel tests in order to discover life-saving treatments and diagnostics.
“ADL houses a lab structure for clinical investigators to evaluate new technologies, advance analytics and to foster collaboration between outside companies and Mayo investigators to support the clinical practice,” says Benjamin Kipp, Ph.D., director of the Advanced Diagnostics Laboratory.
The nimble structure of the laboratory, which is jointly supported by Mayo Clinic’s Department of Laboratory Medicine and Pathology and the Center for Individualized Medicine, allows the researchers to be flexible and quickly respond to the emergent pandemic.
Six months in, teams of Mayo scientists are at the forefront of innovative COVID-19 diagnostics, working to unravel the complexities of the novel virus and diagnose it quickly. Some of the teams’ innovations include antibody (blood) and viral antigen testing, patient immune response stratification, point-of-care diagnostic testing, tissue diagnostics, self-collection kits and data analytics/bioinformatics, to name a few.
“I am pleased that many of our Mayo colleagues have utilized the lab to evaluate many unique COVID-related tests and I am grateful that a few of these tests have recently been transferred to the clinical laboratories to help patients,” Dr. Kipp says.
Combatting Covid-19 with innovative tests
COVID-19 test developments are transpiring inside the state-of-the-art laboratory in One Discovery Square, located in the heart of downtown Rochester, Minn., where highly specialized teams of pathologists, clinical laboratory scientists, technologists, project managers and other experts, focus on specific clinical applications.
Tracking neutralizing antibodies
In one major milestone, ADL scientists have developed a SARS-CoV-2 neutralizing antibody test in support of nationwide efforts to find treatments and vaccines for COVID-19. The new test measures the level of neutralizing antibodies against SARS-CoV-2. Neutralizing antibodies represent those antibodies that can inactivate viruses and have been demonstrated to provide immunity against reinfection in other infectious pathogens. Studies to understand protective immunity in SARS-CoV-2 are ongoing. Plans are underway to develop a second version of the assay to improve performance and throughput.
John Mills, Ph.D., co-director of the Neuroimmunology Lab, was brought in to lead the team, with support from Elitza Theel, Ph.D., director of the Infectious Diseases Serology lab, and in collaboration with Stephen Russell, M.D., Ph.D., a Mayo Clinic colleague and entrepreneur at Vyriad, Inc.
"The neutralizing antibody test is a critical addition to our COVID-19 testing, expanding on the capabilities of the molecular tests used to diagnose active infection and the serology test, which indicates previous infection by identifying antibodies for the SARS-CoV-2 virus," says William Morice, II, M.D., Ph.D., chair of the Department of Laboratory Medicine and Pathology and president of Mayo Clinic Laboratories.
Detecting SARS-CoV-2 exposure with dried blood spots
Another approach for large scale testing involves validating dried blood spots (DBS) as a specimen source for self-collection. DBS have been used in newborn screening since the 1960s, intermittently also to detect antibodies (e.g. HIV). A laboratory group involved in innovation has validated the use of this material for serology testing to determine if a patient has been exposed to SARS-CoV-2. This was launched in June and was used to provide testing for more than 30,000 Mayo employees as part of a seroprevalence study.
“The validation of the use of DBS with serology testing was an overall team effort including people of different backgrounds, and most of whom still have never met in person but are united in our commitment to meet the need of patients here, there and everywhere, including their own homes,” says Dietrich Matern, M.D. Ph.D., co-director of the Biochemical Genetics Laboratory, Division of Laboratory Genetics and Genomics.
Repurposing existing technology
In another test project, ADL researchers are using existing technology, digital droplet PCR (ddPCR), to see if it would be more sensitive than current qPCR technologies for the detection of SARS-CoV-2 and whether having a quantitative viral measurement would monitor patients’ natural progression of COVID-19 and response to therapy. ADL used different reagents to avoid supply chain challenges.
With the support of Joseph Yao, M.D., director of the Hepatitis/HIV Serology Laboratory, and Ann M. Moyer, M.D., Ph.D., co-director of the Personalized Genomics Laboratory, the quantitative SAR-CoV-2 RNA test by ddPCR has now been developed and offered for research use with strong interest from the biopharmaceutical market to help in drug development.
Launching at-home self-collection tests
Another innovation project is focused on self-collection devices for molecular and serologic testing . These validated collection procedures would make testing more accessible to patients and open up opportunities for direct-to-consumer and consumer-initiated channels for Mayo Clinic Laboratories.
“The team is evaluating the use of a mid-turbinate nasal swab, which is 3D printed at Mayo,” says Bobbie Pritt, M.D., division chair of Clinical Microbiology. “The 3D printed swabs serve to mitigate the risk from future supply chain shortages of the commercially available swabs.”
Redefining innovation to combat COVID-19
ADL seeks to provide an understanding of COVID-19 and minimize its impacts on the needs of the patients when it comes to laboratory testing. The neutralizing antibody test was its first to go through the lab from inception to test implementation. The test serves as a “how to” guide in developing new tests in a safe, innovative and timely manner. These advances are possible through the collaborative team effort within the Advanced Diagnostic Laboratory.
“I have been thoroughly impressed with the teamwork displayed by all the different COVID innovation teams during this pandemic and expect continued success moving forward,” Dr. Kipp says.
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