Testing Needs for COVID-19 and Beyond

Chairperson: Bryan Bothwell, Director, Strategy and Business Development, Qorvo Biotechnologies

11:00 Status, Issues, and Unmet Needs for SARS-CoV-2 RNA and Serology Tests

Mickey Urdea, PhD, Founder and Partner, Halteres Associates

The presentation will focus upon the status and issues associated with SARS-CoV-2 RNA and antibody testing. The development of diagnostics tests for SARS-CoV-2 infections has moved at an astonishing and unprecedented pace, with nearly one thousand COVID-19 tests now on the international market. In many cases, manufacturers weren’t completely clear what the use cases for these tests would be because the medical community wasn’t clear either and in some cases it still isn’t. We simply don’t know as much as we would like to about the natural history of the virus, but the picture is coming into focus.

Viral RNA testing is the current mainstay of SARS-CoV-2 infection diagnosis, but there are problems with many of the tests. There are reports of 20% or more false negative results in routine testing. Manufacturers made their best guesses for the segments of the viral genome that would be best suited for PCR and other amplification technology primer/probe design, but there is little consensus. Commercial tests range in limits of detection by nearly 100-fold. Manufacturers are responding with test redesigns. Sample collection with nasopharyngeal swabs poses problems for proper sample collection due to occasional improper sampling technique and the pain inflicted on patients during swabbing. There are trends to alter sample types and collection methods that are improving the situation.

Many serology tests have been introduced, but recently the FDA removed 28 of them from the US market. Most of the immunoassay products are designed to detect anti-SARS-CoV-2 IgG; however, there are also assays for IgM and IgA. These tests are used to help stage the infection, determine previous exposure, and conduct surveillance in sentinel populations. IgG tests are applicable to all three applications, whereas IgM and IgA are probably most useful in staging disease. Commercial tests vary in their sensitivity and specificity. Automated central lab tests tend to have better performance than decentralized tests, but there is no fundamental reason that this must persist. Since viral RNA can persist for some time after IgG appears and symptoms disappear, confirmation of viral clearance with an RNA test in IgG positive patients is warranted.

A major issue with serology tests is that there are often false positive results. In low prevalence settings, when used for previous exposure or surveillance it is possible to find more false positive results than true positive results. It is difficult to assess whether a result is one or the other. Algorithms using repeat testing or two separate serology tests for each person tested are fraught with issues due to our lack of knowledge of test design. We need better designed tests to increase performance.

The presence of IgG could be an indication of at least temporary immunity to reinfection, although it is not likely that all IgG positive persons are immune. Antigen specificity (e.g., spike versus nucleocapsid) and antibody titer are likely to be useful additions to simple qualitative detection of IgG, although these measures will need to be correlated with antibody neutralization assays in vitro.

11:20 COVID-19: Laboratory Medicine’s Response to Assist in Diagnostics, Patient Management, and Outcomes Assessment

Fred S. Apple, PhD, DABCC, FACSM, Co-Director, Clinical & Forensic Toxicology Laboratory, Hennepin Healthcare/Hennepin County Medical Center; Principal Investigator, Cardiac Biomarkers Trials Laboratory (CBTL), Hennepin Healthcare Research Institute (HHRI); Professor, Laboratory Medicine & Pathology, University of Minnesota

The presentation will address the role of the Clinical Laboratory in providing COVID-19 laboratory testing and education to providers and patients for: a) appropriate specimen collection and PCR diagnostic testing, b) implementation of serology antibody screening with the multitude of testing options available, c) role of serology biomarkers such as cardiac troponin and IL-6 in the management of hospitalized patients to assess risk and improve outcomes.

11:40 The Future of Near Patient Testing in a COVID-19 World

Bryan Bothwell, Director, Strategy and Business Development, Qorvo Biotechnologies

The global COVID-19 pandemic has highlighted significant gaps in the availability of high-quality testing at the point-of-care (POC). Users need a minimal number of platforms that offer high assay range across the clinical spectrum, not just covering the suite of COVID-19 testing needs, but in associated cardiac, infectious disease, and hormone testing areas as well. These solutions need to offer similar performance to central labs to give clinicians confidence in the data for patient diagnosis and treatment. For COVID-19 specifically, there is a need to enable semi-quantitative results for antibody testing as levels matter. This presentation will address the suite of tests needed to address the COVID-19 timelines and disease spectrum. It will then highlight the performance observed on the Qorvo Biotechnologies platform and describe how that performance translates to closing the market need gaps identified for ubiquitous POC testing.

12:00 Q&A

Speaker Biographies

Fred S. Apple, PhD
DABCC, FACSM, Co-Director, Clinical & Forensic Toxicology Laboratory, Hennepin Healthcare/Hennepin County Medical Center; Principal Investigator, Cardiac Biomarkers Trials Laboratory (CBTL), Hennepin Healthcare Research Institute (HHRI); Professor, Laboratory Medicine & Pathology, University of Minnesota

Dr. Apple’s applied research has focused in the area of cardiac biomarkers involving acute coronary syndrome, heart failure, and most recently COVID-19 and forensic toxicology. His CLIA-certified research laboratory is the “Cardiac Biomarkers Trials Lab” at the Hennepin Healthcare Research Institute of Hennepin County Medical Center/Hennepin Healthcare. Dr. Apple has served as Associate Editor of Clinical Chemistry for the past 25 years; Member since 2000 of the ‘Universal Definition of Myocardial Infarction and Myocardial Injury’ Global Task Force; Chair of the IFCC Committee on Clinical Application of Cardiac Biomarkers; Member of the AACC Academy Laboratory Medicine Practice Guidelines for Myocardial Infarction and Heart Failure; Member of the Steering Committee of the British Heart Foundation HighSTEACS trial; PI of the UTROPIA and CONTRAST clinicaltrials.gov studies; Member of the Institute of Medicine’s Committee on Qualification of Biomarkers as Surrogate Endpoints of Chronic Disease Risk; Member of the NHLBI Working Group for Onsite Tools and Technologies for Clinical Cardiovascular Research and Point-of-Care; and Program Co-Director of the Clinical Chemistry COMACC Fellowship at Hennepin County Medical Center.

Bryan Bothwell
Director, Strategy and Business Development, Qorvo Biotechnologies

Bryan Bothwell is Qorvo Biotechnologies’ Director of Strategy and Business Development – with responsibility for new market, technology, and customer development worldwide. Prior to Qorvo Biotechnologies, he held various senior marketing and business development roles at Intel, TriQuint, and then Qorvo (TriQuint and RFMD merger), with a primary focus on identifying differentiated technology cores and translating those into product ventures in areas like 5G. He received undergraduate degrees in Biology/Biochemistry from the University of Portland, and master’s degrees in Electrical Engineering and Business Administration from Oregon Health Sciences University and Babson College respectively.

Mickey Urdea, PhD
Founder and Partner, Halteres Associates

Dr. Urdea is Founder and Partner for Halteres Associates. He also founded and served as Chief Executive Officer of Tethys Bioscience, a proteomics-based diagnostics company that has been involved in the prevention of type-2 diabetes (assets acquired by HDL), and was CEO of Quantum Dots Corporation (assets acquired by Life Technologies). Additionally, Dr. Urdea is a founder and the Chairman of Catalysis Foundation for Health (CFH), a non-profit organization addressing gaps in global healthcare caused by inefficiencies in disease diagnosis and monitoring; CFH is developing potential biomarkers for tuberculosis bacterial load with a grant for the Bill & Melinda Gates Foundation. Dr. Urdea is a member of the University of California at San Francisco Leadership Council for Global Health. He serves as a consultant to the life sciences industry and is on the scientific advisory boards and boards of directors of a number of biotechnology and diagnostics companies. Prior to his current activities, Dr. Urdea founded the Nucleic Acid Diagnostics business at Chiron Corporation, where he pioneered viral load assays for the human hepatitis B, hepatitis C, and immunodeficiency viruses; his team introduced the first commercial viral load assays for all three viruses. Dr. Urdea also headed the Oncology Diagnostics business unit at Chiron. He then became business head of the Molecular Diagnostics group and Chief Scientific Officer at Bayer Diagnostics. He has served as an advisor to the Bill & Melinda Gates Foundation for over ten years. Dr. Urdea is an author on over 200 peer-reviewed scientific publications and has more than 125 issued and pending patents. He received his BS in Biology and Chemistry from Northern Arizona University, his PhD in Biochemistry from Washington State University, and had an NIH postdoctoral fellowship at the University of California at San Francisco.