Background: Cell-free next-generation sequencing (cfNGS) may have a unique role in the diagnosis of infectious complications in immunocompromised hosts. The rapid turnaround time and non-invasive nature make it a promising supplement to standard of care.Methods: This retrospective, observational single-center study at a tertiary care medical center in Virginia investigated the use of cfNGS in clinical practice. Patients over age 18 years with cfNGS performed for any indication were included. The primary outcome was detection of bacteria and/or fungi on cfNGS. The secondary outcomes were concordance, and abundance of fungal and bacterial organism concentration detected over time from symptom onset, and clinical impact.Results: Thirty-six patients (92% immunosuppressed) were identified and included.Twenty-one (58%) tests detected one to five organisms (14/21 bacteria, 8/21 fungi, and 6/21 viruses). The clinical impact of cfNGS was positive in 52.8% of cases, negative in 2.8%, and negligible in 44.4%. Positive tests prompted therapy changes in 12 of 21 patients; six of 20 bacteria and seven of eight fungi identified were considered clinically pathogenic. Three bacteria identifications and six fungi identifications prompted targeted treatment. When fungal species were not identified by cNFGS, antifungal de-escalation occurred in seven patients.Conclusion: cfNGS assisted in critical management changes, including initiation of treatment for identified organisms and antimicrobial de-escalation. Its non-invasive nature and rapid turnaround time make this an important adjunct to standard of care testing that may assist in providing earlier, targeted therapy, especially when opportunistic pathogens remain high on the differential diagnosis.

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Introduction: ST elevation myocardial infarction (STEMI) and gastric perforation are emergencies with progressively higher mortality without emergent intervention. Here we present a case of gastric ulcer perforation presenting as an apparent inferoposterior STEMI. Case: A 63-year-old male with hypertension presented with two days of intermittent abdominal pain. While awaiting imaging, the patient developed acute inferoposterior STEMI (figure 1). In route to the cardiac catheterization lab, abdominal CT was emergently reported as gastric ulcer perforation (figure 2). Incorporating multidisciplinary discussions with the cardiac critical care attending, interventionalist, and surgeon, exploratory laparotomy was pursued instead of cardiac catheterization, and the perforation was repaired. Repeat EKG after surgery showed resolution of ST elevations (figure 3) and serial troponins were negative. With no evidence of coronary ischemia, further workup was deferred. Conclusion: The unique aspects of this case include how an acute intra-abdominal process can mimic an inferoposterior STEMI and a rapid multidisciplinary approach to decision-making facing two potential concurrent emergencies that was potentially life-saving.

Background Distinguishing COVID-19 Associated Pulmonary Aspergillosis (CAPA) and invasive mold infections (IMIs) from other causes of secondary pneumonia in COVID-19 can be challenging. 1,3-β-D-Glucan and galactomannan are commonly utilized biomarkers for the workup of IMIs but are limited by a lack of specificity and sensitivity respectively. Cell-free plasma next-generation sequencing (cfNGS) is a promising non-invasive approach that can provide direct detection of pathogens in patient's serum. This study explored its potential role in the evaluation of secondary pneumonia in patients with COVID-19. Methods We performed a retrospective single-center observational study from March 2020 to December 2021 at Virginia Commonwealth University Medical Center, a 811-bed tertiary care center, to evaluate patients with laboratory confirmed SARS-CoV-2 virus infection who underwent cfNGS for the evaluation of CAPA. CfNGS (Karius, Inc., Redwood City, CA) was performed at the discretion of the clinical provider and we evaluated the test indication, patient history, clinical impact, correlation with serum biomarkers, and 30 day all-cause mortality. Results Thirteen patients were evaluated and none had Aspergillus species detected. One patient had Pneumocystis jirovecii on cfNGS. There was a 76.9% (10/13) concordance rate with patients’ serum fungal biomarkers. CfNGS also detected concomitant organisms in 53.8% (7/13) of our cohort. These data assisted in changes of clinical management for 84.6% (11/13) of patients and lead to the change in antifungal usage in 69.2% (9/13). Conclusion In this study, both negative and positive cfNGS test results assisted in important clinical decision making. cfNGS may have a role in the evaluation of CAPA or other IMIs in patients with COVID-19. Disclosures Megan M. Morales, MD, Karius: Paid speaker.