The COVID-19 pandemic, caused by SARS-CoV-2, has severely impacted the world and our home country with upwards of 26 million cases and over 460,000 deaths to date in the United States.1 Luckily— and, in record time—two vaccines, one by Pfizer and the other Moderna, have been authorized for emergency use by the Food and Drug Administration (FDA). As of February 8, 2021, the Centers For Disease Control (CDC) reported that about 41.2 million Americans have received the first dose of a vaccine.
Research and development teams at pharmaceutical and biotechnology companies across the globe have responded quickly, producing both innovative treatments and solutions to help curb the effects of the virus on the population. As the virus continues its rampage, it is critical that both novel discoveries and ongoing clinical development initiatives continue with the support of SARS-CoV-2 diagnostic and prognostic testing. Here we will discuss several testing and discovery solutions for SARS-CoV-2 and the ways in which diagnostic companies, like ourselves, can support these efforts with retrospective clinical trial analyses, prospective clinical trial enrollment, and longitudinal monitoring for disease evolution.
Ongoing clinical trial efforts will continue to lead to breakthrough results for future virus prevention and improve standard of care for symptom management. To this end, we offer several diagnostic testing solutions, which could positively impact clinical trials involving SARS-CoV-2 and aid in patient monitoring over time.
The FDA Emergency Use Authorization (EUA) allows medical countermeasures, such as in vitro diagnostic devices, to be used in public health emergencies.3 Several diagnostic devices have received FDA EUA designation to test both symptomatic and asymptomatic individuals. Currently, there are three types of in vitro diagnostic devices useful in SARS-CoV-2 testing:
Molecular diagnostic tests are highly accurate and considered the “gold standard” in SARS-CoV-2 testing for determining active infection status.
Many of these tests use some version of polymerase chain reaction (PCR), which allows for sensitive detection of the genetic material. Molecular tests are run on nasopharyngeal, mid-nasal, throat swabs or saliva samples, and typically deliver results in days to weeks, depending on location and testing infrastructure. Benefits of molecular testing also include being able to measure the relative viral load, i.e., the amount of virus present in a person’s body.
The majority of molecular tests for SARS-CoV-2 operate on quantitative PCR or qPCR; however, low viral loads in patient nasal and oral passages have led to a significant number of false negative reports. In partnership with Bio-Rad Laboratories, our team has commercialized a different type of PCR-based SARS-CoV-2 molecular assay, which has been demonstrated to be more sensitive than qPCR, specifically in the reduction of false negatives.4,5
The Bio-Rad SARS-CoV-2 Droplet DigitalTM PCR (ddPCRTM) Test is an absolute measurement technology, detects two regions of the SARS-CoV-2 N gene, and has demonstrated 100% concordance with the CDC authorized assays.6,7 Recently, the FDA created a SARS-CoV-2 Reference Panel to allow for direct analytical comparison of molecular diagnostic tests. The Bio-Rad SARS-CoV-2 ddPCR Test ranks 4th out of 117 assays based on sensitivity.8
A respiratory specimen collection kit for the Bio-Rad SARS-CoV-2 ddPCR Test is sent to our Colorado-based laboratory for processing and results are available 97% of the time within 48 hours. The high sensitivity and absolute quantitation of our ddPCR-based test enables highly sensitive viral load determination with reduced false negatives, qualities that are ideal for pharmaceutical researchers involved in clinical trial analyses. Additionally, ease of use, accuracy, and a fast turnaround time make our test an ideal choice for serial monitoring prior to, during and after infection with the SARS-CoV-2 virus.
Antibody tests use a blood or serum sample to detect past infection with the SARS-CoV-2 virus, which can be detectable for weeks to months post-infection. We offer multiple antibody-based testing methods to assist researchers.
In one instance, we offer the Bio-Rad Platelia SARS-CoV-2 Total Antibody Test, which is based on enzyme-linked immunosorbent assay (ELISA) technology and detects the presence of total immunoglobulins (IgA/IgM/IgG) to SARS-CoV-2.9,10 The assay is based on the SARS nucleocapsid glycoprotein in a one-step antigen capture ELISA. This test has very high sensitivity and specificity, has received FDA EUA authorization, and is available for both clinical and research use.10
Additionally, we recently began offering the cPass™ SARS-CoV-2 Neutralizing Antibody Test as a service, which uses ELISA technology to qualitatively detect neutralizing antibodies to the receptor binding domain (RDB) in the spike protein of SARS-CoV-2. This FDA EUA authorized test is intended to aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection in blood with a high sensitivity and specificity. (FDA) This assay is currently highly applicable for research use to further assess the level of protection that novel vaccines offer between individuals as well as the appropriate timing required between doses.12
Finally, in collaboration with Rush University Medical Center, we offer a research use bead-based immunoassay built on the Luminex bead platform.13 This multiplexed assay can simultaneously evaluate four SARS-CoV-2 antigens in a fully automated workflow. Validation studies, conducted by the team at Rush, demonstrate exceptional sensitivity and overall accuracy (100% and 99.62%, relative to PCR-based tests).13 This multiplex approach is cost-effective, can be run on dried blood samples, and is most suited for use in research studies or pharmaceutical clinical trials.
Antigen tests use nasal or nasopharyngeal swabs to detect specific viral antigens, which imply current infection. Antigen tests are relatively inexpensive and deliver rapid results, often in 15 minutes or less, but are much less sensitive than molecular tests, and antigen tests have a higher potential of missing active infections.
The CDC states that the clinical performance of rapid antigen tests seems circumstance-dependent, but they are relevant for use in large-scale screening and surveillance studies when rapid turn-around time and repeated testing can be used to inform infection prevention and control measures, or to direct additional confirmatory testing be done. We can support studies to cross-validate antigen tests with more sensitive molecular diagnostic testing.
We are excited to pair data with machine learning techniques to offer predictive insight into patient outcomes. Our researchers have been developing machine learning methods to analyze molecular and clinical data using artificial intelligence (AI) for over 15 years. We use our propriety AI platform, the Diagnostic Cortex® system, to aid with data interpretation and make predictions based on the clinical question at hand.
For instance, our team recently discovered and validated three AI-based algorithms for predicting a patient’s risk of adverse events during a COVID-19-related hospitalization. Each test, which incorporates patient demographics, vital signs, and laboratory results, assigns patients into categories of increasing risk (lowest, low, high, and highest) for an individual adverse event: admission to the intensive care unit, diagnosis of acute respiratory distress syndrome (ARDS), and need for intubation. In a blinded, independent validation study, 11% of patients classified as lowest risk for being admitted to the ICU (Intensive Care Unit) ended up being admitted compared to 51% of those classified as highest risk out of a cohort of 330 patients of which 26% were admitted to the ICU.14
We leverage the Diagnostic Cortex system to provide meaningful, predictive information about your ongoing clinical trials and study participants.
We are actively looking for ways we can aid researchers and patients as everyone faces this ongoing COVID-19 pandemic. Biodesix offers multiple diagnostic solutions, including a molecular test and three antibody-testing options, that can be paired with top notch data collection for AI-powered analysis. We can aid in retrospective diagnostic testing and analyses for patient outcome prediction, facilitate prospective clinical trial enrollment, and our solutions can help with longitudinal monitoring as the study proceeds. We continue to develop additional solutions for covid and other diseases and look forward to collaborating with you.
United States COVID-19 Cases and Deaths by State.
Covid Data Tracker
Emergency Use Authorizations for Medical Devices
ddPCR: A more sensitive and accurate tool for SARS-CoV-2 detection in low viral load specimens
Highly accurate and sensitive diagnostic detection of SARS-CoV-2 by digital PCR
Bio-Rad SARS-CoV-2 ddPCR Test Instruction for Use
Emergency Use Authorization (EUA) Letter of Authorization for Bio-Rad SARS-CoV-2 ddPCR Test
SARS-CoV-2 Reference Panel Comparative Data
EUA Letter of Authorization for Platelia SARS-CoV-2 Total Ab Test
Platelia SARS-CoV-2 Total Ab Test Instruction for Use
EUA Letter of Authorization for cPass SARS-CoV-2 Neutralization Antibody Detection Kit
A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2–spike protein–protein interaction
Novel serological test for immune response to SARS-CoV-2 Virus
Predicting Prognosis in COVID-19 Patients using Machine Learning and Readily Available Clinical Data