Investigation of the Delve Detect Cerebrospinal Fluid (CSF) Metagenomic Next-generation Sequencing (mNGS) Test When Used for the Initial Diagnostic Workup of Patients With Suspected Central Nervous System (CNS) Infection

Inclusion Criteria:

1. Must be willing and able to provide informed consent or have a legally authorized representative (LAR) willing and able to provide informed consent for participation in the study:
   1. Adults, 18 years of age or older, must provide informed consent, or if unable to provide consent, must have voluntary informed consent provided by a LAR b. Children < 18 years of age must have informed consent provided by a parent, guardian, or LAR, and: i. If 7 years of age or older, must provide voluntary assent for participation, unless unable to do so If less than 7 years of age, assent should also be obtained, if feasible.
2. Individuals presenting with, or admitted or transferred with, suspected CNS infection with at least 2 of the following clinical signs and symptoms:
   1. Headache
   2. Photophobia
   3. Neck stiffness
   4. Nausea/vomiting
   5. Documented fever ≥ 38°C (100.4°F)
   6. Altered mental status (defined as decreased or altered level of consciousness, lethargy, or personality change) lasting ≥ 24 h with no alternative cause identified
   7. Generalized or partial seizures not fully attributable to a preexisting seizure disorder, identified toxic-metabolic derangement, or alcohol withdrawal
   8. Abnormality of brain parenchyma on neuroimaging suggestive of CNS infection that is either new from prior studies or appears acute in onset
   9. Abnormal spinal cord imaging suggestive of myelitis

Note: The clinical signs and symptoms list above applies to non-infant participants (≥ 1 year old). Infants (< 1 year old) who are suspected of CNS infection may be enrolled if they present with fever ≥ 38°C (100.4°F) OR hypothermia < 36.5°C (97.7°F) AND at least 1 of the following clinical signs and symptoms:

1. Bulging fontanel (soft spot)
2. Lethargy or irritability
3. Refusing to feed or poor feeding
4. Apnea
5. Hypotonia or Hypertonia

Exclusionary participant characteristics:

1. Unable to obtain consent (or assent, as applicable) from potential participant or legally authorized representative (LAR)
2. Established diagnosis of non-infectious etiology responsible for symptoms of meningitis/encephalitis/myelitis, with confirmation prior to lumbar puncture (LP) being performed
3. Established diagnosis of infectious etiology responsible for symptoms with microbiologic confirmation prior to LP being performed

4. Established diagnosis of infectious etiology responsible for symptoms prior to CSF sample being sent for testing with Delve Detect CSF

   Note: participants already consented and enrolled in the study who obtain a positive test result from SOC testing prior to the CSF sample being sent for testing with Delve Detect CSF will be withdrawn from the study and excluded from analysis.

5. Low clinical suspicion for infection with one of the following known diagnoses related to the patient admission prior to LP being performed. Remote history of these diagnoses does not exclude the patient from eligibility:
   1. Trauma
   2. Ischemic or hemorrhagic stroke unless suspected to be due to infectious etiology
   3. Postictal or metabolic encephalopathy
   4. Malignancy without present infection symptoms
   5. Demyelinating disease

   Exclusionary CSF sample characteristics:

6. No evidence of CSF pleocytosis (defined as CSF white blood cell count (WBC) ≥ 5 cells per μL) in the first LP collected.

   Note: Exclusion criterion 4 applies to participants who are immunocompetent or otherwise not known to have a current immunodeficiency or immunocompromised status. Individuals with a current immunodeficiency or immunocompromised status (as defined in Section 9.3) may be enrolled with or without the presence of CSF pleocytosis and continue to final analysis.

7. Insufficient residual CSF volume available for Delve Detect testing (< 500 μL)
8. The residual CSF sample available for testing with Delve Detect CSF was not the first diagnostic LP for the participant's current admission
9. Residual CSF was stored at room temperature for ≥ 6 hours
10. Residual CSF was stored refrigerated (2-8 °C) for ≥ 7 days
11. Residual CSF was stored frozen (≤ -70 °C) for ≥ 90 days
12. Residual CSF experienced more than a cumulative two freeze-thaw cycles