Clarity at Speed
With the ebb and flow of COVID-19, the threat of infectious diseases is more pronounced than ever, especially for highly vulnerable immunocompromised patients. Embedded in a world struck by the pandemic, infections remain the main source of morbidity and mortality in patients with cancer (Elfaituri M.K. et al. J. Clin. Oncol., 2019). Karius pioneered a liquid biopsy test for infectious diseases at a time when acquiring a sample from infected tissue is more challenging than ever before. The Karius Test utilizes genomics and AI to detect over 1,000 pathogens from a single blood draw. It is the only diagnostic test that can non-invasively enable clinicians to diagnose both bloodstream and deep-seated infections anywhere in the body. In contrast, many traditional tests require knowing where the infection is in the body, and samples of infected tissue — neither of which are needed for the Karius Test. This novel test can help overcome the challenges stemming from the diagnosis odyssey, and at the same time have the potential to reduce complications from invasive diagnostic procedures by as much as 63% (Rossoff J. et al. Open Forum Infect Dis. 2019). Clinical evidence shows the Karius Test’s ability to provide a faster time to diagnosis compared to conventional methods. Timing is critical when patients with severe infections may only have hours left to live if the right treatment isn’t given. With this test, physicians have another option to arrive at an accurate diagnosis besides the trial-and-error method of empirical treatment for infectious diseases.
The Karius Test is designed to be fast, accurate, and most importantly, non-invasive. The test only requires 5 mL of blood to detect a pathogen likely causing an infection. This is because it’s based on microbial cell-free DNA (mcfDNA) — fragments of DNA freely circulating in blood, left there by infectious agents. Even when an infection is localized (e.g., heart, lungs, brain), mcfDNA can be detected, albeit in very low concentrations. The power and uniqueness of the Karius test comes from its ability to clearly see and accurately measure mcfDNA in extremely low abundance compared to human DNA. To achieve this feat, The Karius team pioneered ways to remove the background “noise” in the form of human DNA and other contamination. Karius uses AI to make sense of massive amounts of deep DNA data, teasing out specific microbial signatures tied to an infection. The result is a clear, accurate picture of the infection, which could be caused by one or more pathogens from a long list of more than 1000. This list includes culprits of disease, including those pathogens that are very difficult to identify, and Karius continues to add to its database. Once shipped to the Karius lab, the blood sample is analyzed and results sent back to a clinician within a day, allowing patients to be rapidly treated with the optimal treatment for that specific infection. Comparatively, resolving via an accurate diagnosis through standard-of-care (SOC) methods may take weeks to complete.
The amounts of mcfDNA in the bloodstream are difficult to detect and very low. When dealing with detecting and quantifying minute amounts of DNA, Karius scientists had to overcome significant challenges related to high human background, environmental contamination, bias, inaccurate and incomplete genomic reference databases, and high biological homology which may drive false-positive detections. For this, Karius designed proprietary protocols for isolating/ preparing the DNA and controlling for background. They automated liquid handling processes and introduced computational methods to manage and analyze the large quantities of DNA data. Essentially, it was like building a system to put together a very complicated jigsaw puzzle, rapidly and reliably, without properly knowing what the final image is meant to be. At the core of that system is the application of machine learning (ML). Artificial intelligence (AI) and ML play a critical role in identifying which data are trustworthy, and which data should be discarded. Karius used ML to control for the uncertainties in the signal, in the noise, and in the data. Karius also developed ML algorithms to correct biases introduced when making biological measurements, because the act of ‘measuring biology’ distorts the end result. Largely thanks to the advanced ML method the company developed and optimized, Karius can extract value out of deep, complex DNA data to get a clear, accurate picture of an infection. Developing strong statistical tools helped Karius make the right calls in identifying an infection, whether it’s a common pathogen or one that’s rare and difficult to diagnose.
The Karius Test has been validated, both analytically and clinically, in 40+ publications, 70+ abstracts, and 10 clinical trials, including a landmark paper in Nature Microbiology. Clinical data showcasing the multiple applications of the Karius Test have appeared in publications including: Clinical Infectious Diseases, JAMA Oncology, Journal of Infectious Diseases and Epidemiology, Journal of the Pediatric Infectious Diseases Society, and Transplantation and Cellular Therapy. Peer reviewed publications can be found here: https://kariusdx.com/clinical-evidence. In August 2020, Karius announced a multicenter study evaluating the use of its test for pneumonia in immunocompromised patients. Organizations participating in the study include Duke University Health, University of Pittsburgh Medical Center, Fred Hutchinson Cancer Research Center, The University of Texas MD Anderson Cancer Center, City of Hope, the Tulane Cancer Center and Tulane Medical Center; and The University of California San Francisco Medical Center. Karius has several verified success stories -- one particular patient story is detailed in this video: https://vimeo.com/375600924. Another story, reported by AP News, explains the struggle faced by a healthy 40-year-old suddenly battling pneumonia and sepsis, and how he was given a new lease on life due to the Karius Test: https://apnews.com/article/health-science-ap-top-news-fungi-connecticut-4586ee13876d41048ffa9d095b53fd23 .
The Karius Test has transformed the paradigm of diagnosing infectious diseases. With a simple blood test, clinicians can now easily and non-invasively detect pathogens that would have otherwise gone undetected and mitigate patient risk from invasive diagnostic procedures. Karius is helping clinicians save lives, using genomics and AI.
