BioPatch MC100®
September 1, 2022
1969
September 1, 2022KARIUS
Karius is a company focused on generating genomic insights for infectious diseases with a non-invasive test that helps clinicians make rapid treatment decisions. They are a team of clinicians, molecular biologists, data scientists, software engineers, and commercial experts with a shared commitment to improving patients’ health. By using genomics and artificial intelligence (AI) to map a patient’s microbial landscape from a single blood draw, Karius aims for a world where infectious diseases are no longer a threat to the health of humans.
Karius A.I Aspects
Infectious diseases are the second leading cause of death worldwide, and many cases go undiagnosed due to limitations with the current diagnostic methods. Karius pioneered the discovery and application of microbial cell-free DNA (mcfDNA), enabling the non-invasive detection of pathogens throughout the body with its Karius Test. By sequencing cfDNA circulating in the plasma, biopsies and other invasive procedures may be avoided.
Novel genomics and AI are used by the Karius Test from a single blood draw to identify and measure the mcfDNA of more than 1000 clinically relevant pathogens (including bacteria, fungi, DNA viruses, and parasites). CfDNA from pathogens can be found in blood regardless of the site of infection. This test will give the health providers relevant information about the likely types and quantities of infectious microorganisms that could be affecting their patients. The results are typically delivered the day after sample receipt, allowing doctors to better diagnose and treat their patients in a timely manner. Applications include diagnosing invasive fungal and other opportunistic infections in immunocompromised patients and diagnosing infections when invasive procedures are contraindicated or undesired.
The Karius laboratory is CLIA-certified and CAP-accredited to perform high-complexity clinical laboratory testing. Karius maintains high-quality standards and certifications that align with its mission of delivering unprecedented insight to enable physicians to make rapid, life-saving treatment decisions.
Karius’s Solutions
- Higher diagnostic yield: the Karius test has demonstrated superior results compared to blood culture and other microbiological tests.
- Faster time to diagnosis: it can identify etiologies of infections faster than the standard of care diagnostic workup.
- Non-invasive: helps to diagnose deep-seated infections such as invasive fungal infections from a single blood draw.
Understanding How the Test works
Infectious pathogens leave traces of their genetic material in the blood as cell-free DNA (cfDNA). The Karius Test isolates, identifies, and quantifies the previously mentioned genetic material signals in the blood. The testing procedure consists of processing the specimen, sequencing the material with next-generation technology, analyzing the sequencing results, and creating a report.
During specimen processing, cfDNA fragments from the plasma specimen are extracted and converted to shotgun DNA sequencing libraries. Afterward, Illumina NextSeq technology is used to sequence the DNA. Lastly, the extracted data is analyzed, and each pathogen’s absolute concentration of cfDNA is calculated. This data is used to compare against control samples and determine the degree of the pathogen’s contribution to the cfDNA specimen and its relevancy. The report only includes the specimens detected to have a relevant amount of genetic material in the cfDNA sample. Relevancy is determined by controls that are run alongside every sample batch analysis. Reporting entails confirming adherence to quality control indicators during the processing and analysis of the specimen. After quality is verified to an acceptable performance standard, the results are faxed to the ordering institution, usually within one day of specimen receipt.
Infectious pathogens leave traces of their genetic material in the blood as cell-free DNA (cfDNA). The Karius Test isolates, identifies, and quantifies the previously mentioned genetic material signals in the blood. The testing procedure consists of processing the specimen, sequencing the material with next-generation technology, analyzing the sequencing results, and creating a report.
During specimen processing, cfDNA fragments from the plasma specimen are extracted and converted to shotgun DNA sequencing libraries. Afterward, Illumina NextSeq technology is used to sequence the DNA. Lastly, the extracted data is analyzed, and each pathogen’s absolute concentration of cfDNA is calculated. This data is used to compare against control samples and determine the degree of the pathogen’s contribution to the cfDNA specimen and its relevancy. The report only includes the specimens detected to have a relevant amount of genetic material in the cfDNA sample. Relevancy is determined by controls that are run alongside every sample batch analysis. Reporting entails confirming adherence to quality control indicators during the processing and analysis of the specimen. After quality is verified to an acceptable performance standard, the results are faxed to the ordering institution, usually within one day of specimen receipt.
Applications of the Karius Test
CfDNA technology has been used successfully in non-invasive prenatal testing, organ transplant rejection screening, and oncology liquid biopsies. The Karius Test has been beneficial in diagnosing and treating immunocompromised patients, cases of complicated pneumonia, and endocarditis.
Financials Aspects of Karius
SoftBank’s second Vision Fund has led a new $165 million funding round for Karius. According to a filing made by the company to the state of Delaware, the Karius Test is already being used in more than 100 U.S hospitals, contributing to the funding rounds that recently valued the company at over $700 million.
The company reports that the price list for the test was $2000 for hospitals. Karius hopes to expand the commercial outreach of the test with existing investors Khosla Ventures and LightSpeed Venture Partners, as well as the added participants from the series B funding. Through the funding, the company will also focus on further clinical testing to build on previous studies of the Karius test.
Karius Test-imonials
Rapid, Non-invasive Diagnosis of Balamuthia mandrillaris encephalitis by a Plasma-Based Next-Generation Sequencing Test
Balamuthia mandrillaris is a free-living organism found mainly in soil and water. The amoeba can infect the body through open wounds or by inhalation. Infected patients develop encephalitis months to years after having cutaneous Balamuthia. Specific diagnosis of Balamuthia encephalitis can be challenging because it usually requires a brain biopsy.
A patient who presented to the hospital with complaints of left-sided weakness, persistent seizures, headaches, confusion, and no improvement with empiric treatment,
Rapid, Non-invasive Diagnosis of Balamuthia mandrillaris encephalitis by a Plasma-Based Next-Generation Sequencing Test
Balamuthia mandrillaris is a free-living organism found mainly in soil and water. The amoeba can infect the body through open wounds or by inhalation. Infected patients develop encephalitis months to years after having cutaneous Balamuthia. Specific diagnosis of Balamuthia encephalitis can be challenging because it usually requires a brain biopsy.
A patient who presented to the hospital with complaints of left-sided weakness, persistent seizures, headaches, confusion, and no improvement with empiric treatment,
had a sample of peripheral blood plasma taken and sent to Karius Clinical Laboratory Improvement Amendments for NGS. McfDNA was extracted from plasma, and sequencing was performed. The samples were positive for B. mandrillaris.
With poor outcomes, early diagnosis of cases like this one could improve patient outcomes by allowing the initiation of definitive treatment.
Identification of Bartonella vinsonii using Next-Generation Sequencing in a Patient With Culture-Negative Endocarditis
Bartonella is a gram-negative bacteria species that infects mammals and can spread through various arthropod vectors, including fleas and ticks. Bartonella species are difficult to grow under standard conditions for bacterial culture.
The case reported was a 20-year-old man with primary concerns of shortness of breath and tea-colored urine. Recent symptoms included chest pain, worsening fatigue, dyspnea, and nighttime cough.
Laboratory tests for infectious etiologies and cultures were taken from blood, urine, and stool. A blood sample was sent to Karius Laboratory for NGS on the fourth day of hospitalization. The test detects pathogenic species by identifying cell-free DNA and aligning the sequences to a pathogen dataset. On day 6 of hospitalization, the initial NGS test resulted positive for B. vinsonii species. Serial NGS tests were performed to quantitate the DNA signal to monitor response to antibiotic treatment. Bartonella vinsonii species were undetectable within six weeks of treatment.
Rickettsia Typhi Detection Using Cell-Free Next-Generation Sequencing
Murine typhus is a bacterial infection caused by Rickettsia typhi, which is transported by infected fleas that spread the infection from rodents to humans. Symptoms are frequently fever, rash, and headache, but they are often nonspecific.
Rickettsia typhi is diagnosed by the identification of IgM antibodies by indirect immunofluorescence assay (IFA); however, during the first days of infection, IgM is positive in only half of infected patients.
The Karius Test utilizes NGS to detect circulating mcfDNA in plasma. The organism was identified in 121 out of 125 tests with a sensitivity of 97.5% and a corresponding positive predictive value of 99% (121 of 122).
Rickettsia Typhi Detection Using Cell-Free Next-Generation Sequencing
Murine typhus is a bacterial infection caused by Rickettsia typhi, which is transported by infected fleas that spread the infection from rodents to humans. Symptoms are frequently fever, rash, and headache, but they are often nonspecific.
Rickettsia typhi is diagnosed by the identification of IgM antibodies by indirect immunofluorescence assay (IFA); however, during the first days of infection, IgM is positive in only half of infected patients.
The Karius Test utilizes NGS to detect circulating mcfDNA in plasma. The organism was identified in 121 out of 125 tests with a sensitivity of 97.5% and a corresponding positive predictive value of 99% (121 of 122).
had a sample of peripheral blood plasma taken and sent to Karius Clinical Laboratory Improvement Amendments for NGS. McfDNA was extracted from plasma, and sequencing was performed. The samples were positive for B. mandrillaris.
With poor outcomes, early diagnosis of cases like this one could improve patient outcomes by allowing the initiation of definitive treatment.