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

Inclusion Criteria: * Basket Protocol\* All participants must meet inclusion 1. Age ≥18 2. 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 3. Treating provider suspects infection and plans to obtain usual care diagnostic testing for the suspected infection (i.e., microbiologic testing) 4. Willing to provide research samples via blood draw 5. Willing and able to provide informed consent 6. 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: <!-- --> 1. 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 2. 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: 1. 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 2. 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: 1. Active symptoms are likely attributed to non-infectious causes. 2. 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: <!-- --> 1. 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. 2. 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: 1. 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. 2. 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.