What is Karius?

- About Karius

Karius is a life sciences company located in Redwood City, California focusing on transforming infectious disease diagnostics with genomics. Our next-generation sequencing test for microbial cell-free DNA provides clinicians with a comprehensive test capable of identifying more than 1,000 pathogens directly from blood. Karius was founded in 2014 based on years of research conducted at the Quake lab at Stanford.

The Karius test has been commercially available since December 2016.

The KariusTM Test uses next-generation sequencing (NGS) and analytics for the broad and rapid detection of microbial cell-free DNA through a standard blood draw. Unlike conventional culture and panel testing methods that identify a narrow range of pathogens, the Karius Test can detect more than 1,000 pathogens. Our pathogen database is curated for sequence quality and clinical relevance. The test is broad-based, looking for all pathogen signals, which means that co-infections can be detected.

Pathogens we can detect are: Bacteria, Fungi, DNA Viruses, and Eukaryotes (including protozoa). The complete list can be found here: kariusdx.com/pathogenlist

The Karius Test is an unbiased, non-targeted enrichment of pathogen signals. It involves 3 processes: 1) sample processing, 2) next-generation sequencing, and 3) sequence analysis.

During sample processing, cell-free DNA fragments from the plasma sample are extracted. Next, the DNA undergoes whole genome sequencing using Illumina NextSeq technology. Finally, during analysis, the relative abundance of pathogen sequences is calculated.

Karius reports organisms that are present in the specimen in statistically significant amounts. One or multiple microorganisms may be on the report if they are detected at statistically significant levels.

Why cell-free DNA?

- Clinical Questions

By sequencing cell-free DNA, biopsies may be avoided, and dead or dying pathogens from deep infections sites can be detected.

Cell-free DNA technology has successfully been used in noninvasive prenatal testing (NIPT) and liquid biopsies in oncology.

The Karius Test has widespread applications such as:

  • Detecting pathogens in culture-negative infections including sepsis, endocarditis and infections with fastidious organisms, as well as for patients pre-treated with antibiotics
  • Identifying deep-seated infections such as invasive fungal infections that would otherwise require invasive biopsies
  • Enabling targeted antimicrobial therapy and promoting stewardship
  • Monitoring immunocompromised patients susceptible to a broad range of pathogens, including stem-cell transplant recipients and patients with febrile neutropenia

What is your test performance?

- Clinical Questions

The performance of the Karius Test was determined based on adjudication from an independent clinician panel in the SEP-SEQ study, which compared the performance of the Karius Test to blood culture and also to a clinical composite reference standard of all microbiologic testing and clinical diagnosis. Specimens were obtained from 350 patients with suspected sepsis.
Based on this study:

  • The Karius Test has a diagnostic sensitivity of 92.9%.
  • The test was found to detect a potentially sepsis-causing pathogen three times more often than initial blood culture alone in patients with suspected sepsis.
  • The analytical specificity of the test is 99.4%.

Our limit of detection is established in terms of microbial cell-free DNA (cfDNA) fragments and is 0.7 pg/mL microbial cfDNA. Because this LoD is based on detection of fragments of DNA in cell-free plasma, the value is not comparable to the LoD of other diagnostic assays. There is currently no other validated test that detects pathogen DNA in a small sample of cell-free plasma like the Karius Test.

There is no established relationship yet between the concentration of cfDNA in plasma and the number of viable microbes in blood. Numerous factors, including, antimicrobial treatment, location of the infection, type of microorganism, can change the relationship between viable microbes and cfDNA from these microbes.

The Karius Test can detect cell-free DNA (cfDNA) from dead and dying pathogens released into the bloodstream. Therefore, the cfDNA signal of a pathogen may still be detected even when a patient has been pre-treated with antibiotics.

Currently, the Karius Test is only validated for blood plasma samples. However, this does not mean that we can only detect bloodstream infections. We have found that even when an infection is localized in the CSF, in the lung, or in a deep abscess, pathogen cfDNA from that infection can be detected in the plasma.

At this time, the Karius Test does not provide information about antimicrobial resistance. However, we are continually working to improve our test. If there is a specific resistance gene that you are interested in, please let us know by writing to help@kariusdx.com.

Package the specimen along with a printed Karius Test Requisition Form using packaging and transportation supplies provided by Karius. Specimens should be shipped at ambient temperature and should arrive at Karius within 4 days (96 hours) of draw.

We recommend that specimens are shipped via FedEx First Overnight to ensure that the specimens are received at Karius before 8:30 am. Karius covers FedEx First Overnight fees. You can use FedEx pre-printed airbills included in our kits or select the option to print a FedEx label when you submit the requisition online.

You can reach us by phone at 1-866-452-7487 or by email at help@kariusdx.com

Karius is CLIA-certified and CAP-accredited. We are licensed in CA, PA, FL, MD, and RI, and our test is available in all US states except NY. Please see https://www.kariusdx.com/licensure for more details.

Typically, samples received at our laboratory by 8:30 AM Monday through Friday are reported the next day (Monday-Saturday).

Our laboratory process requires that a specimen being tested passes all of our stringent quality control (QC) metrics before its result is reported. If a specimen fails to meet any of the internal QC standards, it is re-processed. This means the reporting of the result will be delayed.

Please contact Karius for information on pricing.

Please contact Karius at help@kariusdx.com to create an account. To onboard your institution, we will need the following information:

  • Institution Name
  • Address
  • Phone Number
  • Fax Number
  • Billing Contact
  • Email Address for login credentials

Our preferred method of specimen collection is in a BD Vacutainer™ Plasma Preparation Tube (PPT).

  1. Collect 5 mL whole blood in PPT tube. and invert 8-10 times.
  2. Within 6 hours of the draw, spin PPT tube at 1,100 RCF for 10 mins at room temperature. (Separated plasma in PPT tube is stable at room temperature for up to 96 hours after draw).
  3. Ship specimen at ambient temperature via FedEx First Overnight service to Karius.

You can find more information about specimen collection here: https://www.kariusdx.com/order/lab

If the gel plug in the PPT tube does not move to separate the cells from the plasma, the tube should be re-centrifuged at a higher speed. Check to make sure that the setting on your centrifuge is set at RCF or g, and not RPM before re-centrifuging at 1,100 RCF (g). In most centrifuges, a speed between 2,500-4,500 RPM should move the gel plug.

If the specimen is collected in a PPT tube, after centrifugation, the tube can be frozen as is without transferring the plasma into a separate tube. If the specimen is collected in a K2-EDTA tube, transfer the plasma into a sterile polypropylene tube after centrifugation before freezing.

If the specimen is frozen and shipped on dry ice, the specimen can be received at Karius anytime after the draw.  

Samples are rejected if:

  • They do not meet our minimum volume criteria (600 uL of plasma)
  • Plasma was separated from whole blood >6 hours after draw
  • Plasma was received at Karius at ambient temperature  >4 days after draw
  • Specimen has fewer than 2 patient identifiers on the tube
  • Specimen was collected in a tube beyond its expiration date
  • Specimen has incomplete or improper separation of plasma

If you already have login credentials given to you by Karius, please login using those credentials here: https://online.kariusdx.com.

If you don’t have a login, please contact Karius at help@kariusdx.com.

On the Karius Test report, the results include the name of any microorganism(s) detected at statistically significant levels, the DNA molecules per microliter (MPM), and the reference MPM range. MPM refers to the number of microorganism DNA fragments present in one microliter of plasma. The reference range represents the 97.5th percentile MPM concentration detected in plasma samples from asymptomatic individuals for each microorganism present. 

A positive result will list the MPM detected for each microorganism in the patient specimen received at Karius. MPM values that are lower than the corresponding reference range suggest that the microorganism may not be the cause of an infection, or that the value was decreased due to antibiotic pre-treatment. A negative result means that no cell-free DNA of any microorganisms in our database was detected in statistically significant amounts. This does not mean that the patient is infection-free.

As with any test, the results must be interpreted given the patient's clinical context.

Karius does not provide recommendations on the management or treatment of specific patients. As with any diagnostic test, the Karius Test should be interpreted in the context of your patient’s clinical picture to determine clinical significance.

Our Medical Affairs team is always available for consultation and happy to provide you with references to literature that describe the pathogen, its spectrum of disease, and treatment options. This information might help you determine how best to use the Karius Test result to guide the care of your patient.

Please contact Medical Affairs at medical@kariusdx.com or 866-452-7487.

There are two reasons why a “No call” is reported.

  1. The specimen did not meet the our minimal acceptance criteria and was rejected upon receipt
  2. The specimen did not meet our internal quality control standards during its testing