Microbial Cell-free Metagenomic Sequencing for Suspected Infections in Adult Immunocompromised Outpatients

Inclusion criteria

• Basket Protocol\
• All participants must meet inclusion
• Included in one of the following immunocompromised groups: Solid organ transplant recipient (SOT) on chronic immunosuppression; Diagnosed with hematologic malignancy (HM) and/or recipient of a hematopoietic cell transplant (HCT); Diagnosed with a solid tumor and on specific types of active treatment; Recipient of drugs or novel biologics causing chronic immunosuppression; Diagnosed with an HIV infection; Diagnosed with inborn errors of immunity
• Treating provider suspects infection and plans to obtain usual care diagnostic testing for the suspected infection (i.e., microbiologic testing)
• Willing to provide research samples via blood draw
• Willing and able to provide informed consent
• Presenting for evaluation in the outpatient setting (includes telehealth) \*For Participants enrolled in Sub-Protocol A- Solid Organ Transplant\
• All Sub-Protocol A subjects must meet the following: <!-- -->
• Solid organ transplant recipient on transplant immunosuppression Non-lung recipients must meet one or more of the following characteristics: \<1 year from transplant; Augmented immunosuppression for suspected or confirmed rejection within the last 6 months; Confirmed systemic infection in last 6 months
• Suspected infection defined by one or more of the syndromes: Cardiac; Lower Respiratory; Gastrointestinal / Hepatobiliary; Genitourinary; Neurologic / Ophthalmologic; Skin / Soft tissue / musculoskeletal; Not Otherwise Specified
• For Participants enrolled in Sub-Protocol B- Hematological Malignancies and Transplant\
• All Sub-Protocol B subjects must meet the following:
• Is included in at least one of the following groups: Hematologic malignancy (leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma) and at least one of the following: Received chemotherapy or other systemic anti-cancer therapy associated with immunosuppressive effects within 90 days (e.g., monoclonal antibodies associated with B-cell or plasma cell depletion, bi-specific t-cell engagers, BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors) within the last 90 days Note: Checkpoint inhibitors are not included unless given in combination with an immunosuppressive agent; Relapsed disease with chemotherapy anticipated in 60 days; ANC \<500 within the last 72 hours; Hypogammaglobulinemia IgG \<400 within the last 30 days; Allogeneic stem cell transplant for any clinical indication and at least one of the following: Within 1-year post-transplant; On systemic immunosuppressive therapy for GVHD treatment or prophylaxis; Autologous stem cell transplant for hematologic malignancy and at least one of the following: Within 6 months post-transplant; ANC \<500 within the last 72 hours; B cell and plasma cell targeted CAR-T therapy for hematologic malignancy and at least one of the following: Within 6 months of CAR-T cell infusion; CD4 T-cell \<200 within the last 30 days; IgG \< 400 within the last 30 days; ANC \<500 within the last 72 hours; On systemic immunosuppressive therapy for CRS/ICANS
• Suspected infection defined by one or more of the syndromes: Cardiac; Lower Respiratory; Gastrointestinal / Hepatobiliary; Genitourinary; Neurologic / Ophthalmologic; Skin / Soft tissue / musculoskeletal; Not Otherwise Specified

Exclusion criteria

• Basket Protocol\
• All participants must not meet the following:
• Active symptoms are likely attributed to non-infectious causes.
• Any other clinically significant medical condition that, in the opinion of the treating provider, makes participation undesirable, including but not limited to severe psychiatric illness, etc. \*For Participants enrolled in Sub-Protocol A- Solid Organ Transplant\
• All Sub-Protocol A subjects must not meet the following: <!-- -->
• Patients who have been previously evaluated (including via telehealth) for the same clinical signs and symptoms at this institution and pathogen-directed usual care (UC), diagnostic testing was ordered during that prior encounter, with one or more diagnostic test results still pending.
• Patients with a suspected or confirmed primary upper respiratory infection (e.g., viral pharyngitis, sinusitis, or uncomplicated bronchitis) unless there is clinical suspicion of a concurrent lower respiratory or systemic infection requiring further diagnostic evaluation.
• For Participants enrolled in Sub-Protocol B- Hematological Malignancies and Transplant\
• All Sub-Protocol B subjects must not meet the following:
• Patients that have been previously evaluated (including via telehealth) for the same clinical signs and symptoms at this institution and pathogen-directed usual care (UC) diagnostic testing was ordered during that prior encounter with one or more diagnostic tests results still pending.
• Patients with a suspected or confirmed primary upper respiratory infection (e.g., viral pharyngitis, sinusitis, or uncomplicated bronchitis) unless there is clinical suspicion of a concurrent lower respiratory or systemic infection requiring further diagnostic evaluation.