Karius, a leader in metagenomic sequencing for infectious disease diagnostics, unveiled its latest breakthrough: the “Karius Focus | BAL” microbial cell-free DNA (cfDNA) test. This diagnostic tool uses bronchoalveolar lavage (BAL) samples to support clinical identification of pathogens causing pneumonia and other lung infections, particularly in immunocompromised patients.
“Immunocompromised individuals represent a large and growing population in the United States, and they’re poorly served by current diagnostic tools for infectious diseases,” Bradley Perkins, MD, Chief Medical Officer at Karius, told Inside Precision Medicine. “Traditional diagnostics target specific diseases, but these patients are vulnerable to a broad range of infections, including opportunistic pathogens. This unmet need drives our mission.”
For the immunocompromised
For individuals with compromised immune systems, such as those undergoing cancer treatment or organ transplantation, the stakes are incredibly high. “The mortality rate for immunocompromised patients admitted with suspected pneumonia is about 25%,” Perkins emphasized. “This is not just about improving diagnostics; it’s about saving lives.”
The diagnostic challenge lies in the atypical presentation of diseases in these patients. Unlike immunocompetent individuals, who exhibit clear symptoms like cough, fever, and chest pain, immunocompromised patients often lack these hallmark signs due to their weakened immune responses. This makes it difficult for physicians to pinpoint the cause of infection, leading to a diagnostic odyssey of repeated testing with limited success.
“If your immune system is competent, you tend to present to doctors with very well-defined syndromic illnesses,” Perkins noted. “For example, if you have pneumonia, you’ll typically have a cough, fever, and sputum production, along with other signs that guide doctors to a diagnosis. Unfortunately, immunocompromised patients don’t present with these clear symptoms, making it harder to diagnose and treat them effectively.”
Karius has already made significant strides in this field with its plasma-based test, which uses a routine blood sample to identify infections throughout the body. This test demonstrated its potential in the 2023 PICKUP study, where it increased diagnostic yield by 40% compared to traditional methods.
“In the PICKUP study, we compared the Karius plasma test to all other diagnostic tools available over a two-week period,” Perkins noted. “Our non-invasive plasma test alone significantly improved diagnostic accuracy. This was a breakthrough, but we asked ourselves how we could do even better in specific clinical scenarios.”
The plasma-based test’s ability to detect infections throughout the body makes it particularly valuable in cases where the source of infection is uncertain. “The plasma test covers over 1,000 DNA-based pathogens, which allows us to identify infections that might not be limited to one location,” Perkins added. “This is especially critical for immunocompromised patients, where infections can occur anywhere and often simultaneously.”
From blood to BAL
The answer came in the form of the “Karius Focus | BAL” test, which involves introducing saline into the lungs, collecting the fluid, and analyzing it for microbial DNA. While the plasma test scans for over 1,000 pathogens affecting the entire body, the BAL test narrows its focus to more than 500 pathogens known to cause pneumonia and other lung infections.
With just 1 mL of BAL fluid, the diagnostic can detect and classify over 500 pathogens associated with lung infections—all within a single day of sample receipt. This revolutionary test leverages the same microbial cfDNA technology as Karius Spectrum™ but is specifically tailored for diagnosing lung infections. It is designed to rapidly identify the cause of lung infections and improve diagnostic yield compared to standard-of-care testing.
“BAL has long been a widely used procedure for evaluating patients with suspected lung infections, particularly in immunocompromised populations,” Perkins explained. “But standard-of-care testing frequently fails to identify the causative pathogen, often requiring multiple tests and leading to delays in care. Karius Focus | BAL addresses these gaps by providing clinicians with a single, comprehensive answer—delivered quickly and conveniently.”
Perkins elaborated on the technological synergy between the plasma and BAL tests. “What’s exciting is that both tests run on the same technological platform,” he said. “In the lab, the wet lab processes and sequencing are identical. It’s only during the bioinformatics analysis that they diverge, with the BAL test focusing specifically on lung pathogens. This efficiency highlights the robustness of our approach.”
Behind the scenes, the technology powering these tests is nothing short of revolutionary. Karius employs advanced metagenomic sequencing to analyze up to 20 million fragments of microbial DNA from a single sample. These short DNA reads are computationally reconstructed to identify the pathogens present.
“This process is a stunning human achievement,” Perkins remarked. “It’s powered by advancements in computational processing and artificial intelligence. With 20 million fragments of DNA to analyze, the ability to identify the microorganisms causing disease is truly a testament to the power of modern technology.”
The BAL test’s unparalleled pathogen coverage sets it apart from traditional diagnostic tools. “The largest multiplex PCR tests on the market cover about 20 organisms,” Perkins said. “Our BAL test identifies over 500 pathogens that cause pneumonia and other lung infections. This breadth is unprecedented and addresses a critical need in diagnostics.”
Empowering clinical decision-making
The complementary nature of the plasma and BAL tests provides clinicians with a versatile toolkit. The plasma test’s broad coverage across the body makes it invaluable for identifying infections beyond the lungs, while the BAL test excels in pinpointing lung-specific infections. “Depending on the clinical severity and the availability of bronchoscopy, doctors can choose between the plasma test, the BAL test, or both,” Perkins said. “This flexibility ensures that the right diagnostic tool is used for the right patient at the right time.”
The availability of both tests has the potential to impact clinicians significantly. “It’s going to be fascinating to see how doctors decide to use these tools in practice,” Perkins remarked. “Plasma covers the entire body but isn’t as precise for lung-specific infections. BAL, on the other hand, focuses intensely on the lungs and delivers unparalleled diagnostic accuracy for those cases.”
The implications of this innovation extend far beyond the laboratory. By addressing the diagnostic gaps for immunocompromised patients, the microbial cfDNA test could significantly reduce mortality rates and improve patient outcomes. “For patients admitted with suspected pneumonia, timely and accurate diagnosis can mean the difference between life and death,” Perkins stated. “This is a new world for infectious disease diagnostics, and we’re proud to be at the forefront of this transformation.”
The new lung pathogen diagnostic also represents a shift in how clinicians approach lung infections. “Your best chance of getting an infection is through the lungs and the gastrointestinal tract,” Perkins explained. “By directly sampling the lungs with BAL, we’re not just increasing the chances of identifying pathogens—we’re redefining what’s possible in infectious disease care.”
As the new test from Karius becomes available nationwide, it could mark a pivotal moment in the fight against lung infections. With its combination of cutting-edge technology, expansive pathogen coverage, and a focus on patient-centered care, this test may be poised to redefine standards in infectious disease diagnostics.
