493. Incidence and Characterization of Chronic Active COVID Among Patients Infected with the Novel Coronavirus (COVID-19) Receiving B-cell Depleting Therapies (BCDTs)

BACKGROUND: There have been reports of COVID-19 infection characterized by prolonged viral replication [chronic active COVID-19 (CAC)] among immunocompromised patients, including those receiving B-cell depleting therapies (BCDTs). We aimed to characterize the severity and incidence of CAC among patients on BCDTs with COVID-19, and to identify associated risk factors. METHODS: We retrospectively reviewed all patients who received an anti-CD20 BCDT within 1 year of a positive COVID test at University of Utah Health. Demographics, comorbidities, indications, and timing of BCDT were documented. Chart review was performed to characterize the clinical course, including need for hospitalization, COVID-specific therapies, need for ICU and ventilatory support, and mortality. We defined CAC as: (1) despite initial clinical improvement, progression of illness extending beyond 14 days, characterized by ongoing fevers or progressive respiratory failure; or (2) ongoing symptoms with demonstration of absent seroconversion ≥ 14 days into illness. In some patients the diagnosis of CAC was supported by low viral PCR crossing thresholds that occurred ≥ 14 days into illness. Logistic models were used to identify risk factors for CAC among the cohort of patients who survived through the initial period of infection. RESULTS: We identified 66 individuals who received a BCDT within 1 year of a positive COVID test; 29 (44%) were hospitalized, 4 (6%) required ventilation, and 7 (11%) died within 60 days. Among 63 patients who survived their initial COVID course, 16 (25%) had courses compatible with CAC. Nine (56%) who received a BCDT within 1 month before or 2 weeks after their COVID diagnosis developed CAC; OR 7.4 (95% CI 1.7, 31.6, p=0.002). [Image: see text] [Image: see text] CONCLUSION: We clinically observed COVID-19 infection lasting longer than the typical course and propose a definition for CAC. Incidence of CAC was highest among patients who received BCDT within 30 days before or 2 weeks after COVID-19 diagnosis. High suspicion for CAC is warranted among patients receiving these therapies. Additional study is needed to better define risk for CAC among varying immunosuppressed populations and determine whether COVID-specific treatments early in disease may benefit these patients. DISCLOSURES: Hannah Imlay, MD, MS, Gilead Sciences, Inc. (Scientific Research Study Investigator

Positivity of repeat nasal MRSA PCR screening: a single-center experience

Repeating nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reactions (PCRs) within 14 days may increase healthcare costs and inform anti-MRSA antibiotic therapy without known benefit. Within an inpatient admission, our retrospective, single-center evaluation found that conversion from negative to positive on repeat nasal MRSA PCR screen was uncommon (2%)

The Epistemology of the Question of Authenticity, in Place of Strategic Essentialism

The question of authenticity centers in the lives of women of color to invite and restrict their representative roles. For this reason, Gayatri Chakravorty Spivak and Uma Narayan advocate responding with strategic essentialism. This paper argues against such a strategy and proposes an epistemic understanding of the question of authentic- ity. The question stems from a kernel of truth—the connection between experience and knowledge. But a coherence theory of knowledge better captures the sociality and the holism of experience and knowledge

Neutralization assay with SARS-CoV-1 and SARS-CoV-2 spike pseudotyped murine leukemia virions.

Virus neutralization by antibodies is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal murine leukemia virus genome encoding firefly luciferase. This assay design is intended for use in laboratories with biocontainment level 2 and therefore circumvents the need for the biocontainment level 3 that would be required for replication-competent SARS-CoV-2 virus. To validate the pseudovirion assay, we set up comparisons with other available antibody tests including those from Abbott, Euroimmun and Siemens, using archived, known samples. 11 out of 12 SARS-CoV-2-infected patient serum samples showed neutralizing activity against SARS-CoV-2-spike pseudotyped MLV viruses, with neutralizing titers-50 (NT50) that ranged from 1:25 to 1:1,417. Five historical samples from patients hospitalized for severe influenza infection in 2016 tested negative in the neutralization assay (NT50 < 25). Three serum samples with high neutralizing activity against SARS-CoV-2/MLV pseudoviruses showed no detectable neutralizing activity (NT50 < 25) against SARS-CoV-1/MLV pseudovirions. We also compared the semiquantitative Siemens SARS-CoV-2 IgG test, which measures binding of IgG to recombinantly expressed receptor binding domain of SARS-CoV-2 spike glycoprotein with the neutralization titers obtained in the pseudovirion assay and the results show high concordance between the two tests (R2 = 0.9344). SARS-CoV-2 spike/MLV pseudovirions provide a practical means of assessing neutralizing activity of antibodies in serum or plasma from infected patients under laboratory conditions consistent with biocontainment level 2. This assay offers promise also in evaluating immunogenicity of spike glycoprotein-based candidate vaccines in the near future.This research was supported by a seed grant from the University of Utah Vice President for Research and the Immunology, Inflammation, and Infectious Disease Initiative. V.P. and M.C. were supported by NIH grant AI143567-01.S

Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process

Abstract Background Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions. Methods Panelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds. Results Thirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable. Conclusions In the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario

Impact of Implementation of the Core Elements of Outpatient Antibiotic Stewardship Within Veterans Health Administration Emergency Departments and Primary Care Clinics on Antibiotic Prescribing and Patient Outcomes.

BackgroundThe Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use. We report the impact of core elements implementation within Veterans Health Administration sites.MethodsIn this quasiexperimental controlled study, effects of an intervention targeting antibiotic prescription for uncomplicated acute respiratory tract infections (ARIs) were assessed. Outcomes included per-visit antibiotic prescribing, treatment appropriateness, ARI revisits, hospitalization, and ARI diagnostic changes over a 3-year pre-implementation period and 1-year post-implementation period. Logistic regression adjusted for covariates (odds ratio [OR], 95% confidence interval [CI]) and a difference-in-differences analysis compared outcomes between intervention and control sites.ResultsFrom 2014-2019, there were 16 712 and 51 275 patient visits within 10 intervention and 40 control sites, respectively. Antibiotic prescribing rates pre- and post-implementation within intervention sites were 59.7% and 41.5%, compared to 73.5% and 67.2% within control sites, respectively (difference-in-differences, P &lt; .001). Intervention site pre- and post-implementation OR to receive appropriate therapy increased (OR, 1.67; 95% CI, 1.31-2.14), which remained unchanged within control sites (OR,1.04; 95% CI, .91-1.19). ARI-related return visits post-implementation (-1.3% vs -2.0%; difference-in-differences P = .76) were not different, but all-cause hospitalization was lower within intervention sites (-0.5% vs -0.2%; difference-in-differences P = .02). The OR to diagnose non-specific ARI compared with non-ARI diagnoses increased post-implementation forintervention (OR, 1.27; 95% CI, 1.21 -1.34) but not control (OR, 0.97; 95% CI, .94-1.01) sites.ConclusionsImplementation of the core elements was associated with reduced antibiotic prescribing for RIs and a reduction in hospitalizations. Diagnostic coding changes were observed