Review Panel Member Research Articles

The Feeling Rules of Peer Review: Defining, Displaying, and Managing Emotions in Evaluation for Research Funding

Punctuated by joy, disappointments, and conflicts, research evaluation constitutes an intense, emotional moment in scientific life. Yet reviewers and research institutions often expect evaluations to be conducted objectively and dispassionately. Inspired by the scholarship describing the role of emotions in scientific practices, we argue instead, that reviewers actively define, display and manage their emotions in response to the structural organization of research evaluation. Our article examines reviewing practices used in the European Research Council’s (ERC) Starting and Consolidator grants and in the Marie Skłodowska-Curie Action’s (MSCA) Individual Fellowships. These two European funding mechanisms offer different perspectives on the organization of grant evaluation. We conducted interviews with review panel members and analyzed various institutional documents. By drawing on the sociological concepts of feeling rules and emotional work, we demonstrate that reviewers define rules concerning how emotions should be experienced and expressed to ensure the proper functioning of evaluation, and that reviewers experience the need to actively regulate their emotions to comply with these rules. We present four feeling rules concerning the experience and expression of: (1) excitement for novelty during individual evaluation; (2) respect for others’ opinions and the absence of anger in review panels; (3) attentiveness and interest, which are seen as missing in online evaluations. Reviewers also expect ERC candidates to (4) avoid pride and manifest modesty during interviews. These rules demonstrate that proposal peer review is governed by emotional norms, and show the influence of organizational settings and moral requirements on research evaluation.

Conceptualising ‘street-level’ urban design governance in Scotland

This article develops ‘street-level bureaucracy’ theory to conceptualise how policy implementation within urban design governance is shared among actors whose role transcends sectoral responsibilities and motivations. It presents case study research with a Scottish local authority which has made a strategic investment in a placemaking policy agenda, including the creation of an influential design review panel of volunteer experts which exemplifies the wider embrace of private capacity within public governance. The paper identifies the distinctive role of design review panel members in street-level implementation, and shows how their discretion is shaped simultaneously by public and private interests. It concludes that understanding and utilising these micro-level processes provides opportunities for conceptualising policy implementation within a neoliberalising urban governance context, and for addressing the implementation gap between the aims of public urban design policy and the realities of delivery.

Policy Studies Yearbook Annual Review 2022–23: Note from the editor and call for papers

<i>Policy Studies Yearbook Annual Review</i> 2022–23: Note from the editor and call for papers

Patient Reported Impact of Symptoms in Spinal Bulbar Muscular Atrophy (PRISM-SBMA) (S33.007)

Patient Reported Impact of Symptoms in Spinal Bulbar Muscular Atrophy (PRISM-SBMA) (S33.007)

P131 Time to Discontinuation and Effectiveness with Baricitinib in Rheumatoid Arthritis: 12-Month European Data from a Multinational, Prospective, Observational Study

Abstract Background/Aims RA-BE-REAL is a 3-year, multinational, prospective, observational study of adult patients with rheumatoid arthritis (RA) evaluating time-to-discontinuation of initial RA treatment. Baricitinib (BARI), an oral selective JAK1/2 inhibitor, is approved for the treatment of adults with moderate-to-severe active RA. This analysis reports time-to-discontinuation and effectiveness in patients with RA enrolled in Europe following 12M of either BARI, a biologic (b) disease-modifying anti-rheumatic drug (DMARD) or any other targeted synthetic (ts)DMARD, after starting that treatment for the first time. Methods Two cohorts were assessed: patients in cohort A initiated treatment with BARI (2-mg or 4-mg as monotherapy or in combination with any csDMARD) while patients in cohort B initiated any bDMARD (tumour necrosis factor inhibitors [TNFi] or non-TNFi bDMARD) or any other tsDMARD for the first time. Treatment initiation and changes were at the discretion of patient or physician. Time-to-discontinuation for patients in both cohorts were analysed in both bDMARD-naïve and -experienced patients. Response rates for remission and low disease activity (LDA) were determined using the Clinical Disease Activity Index at 12M. Steroid use was collected for both cohorts. This pre-specified interim analysis reports descriptive 12M data using summary statistics, without any inferential testing. Results At 12M, a similar percentage of patients discontinued 2-mg (25.4%) and 4-mg (26.9%) BARI whether as monotherapy (24.7%) or as combination therapy with any csDMARD (28.8%). In cohort B, 42.2%, 44.7%, and 52.3% of patients using TNFi, non-TNFi, and any other tsDMARD, respectively, discontinued treatment at 12M. In both cohorts, patients naïve to b/tsDMARD were least likely to discontinue treatment while those who had more than two previous b/tsDMARD treatments were most likely to discontinue. The most common reasons for discontinuation were primary non-response (Cohort A: 6.3%; Cohort B: TNFi: 8.3%, non-TNFi: 10.6%, any other tsDMARD: 10.6%) and adverse events (Cohort A: 6.3%; Cohort B: TNFi: 5.1%, non-TNFi: 7.5%, any other tsDMARD: 13.6%). At 12M, remission rates were 21.8%, 18.0%, 4.0%, and 18.2% for those on monotherapy treatment with BARI, TNFi, non-TNFi, and any other tsDMARD, respectively. For combination therapy, remission rates were 26.2%, 19.0%, 15.9%, and 13.6% for BARI, TNFi, non-TNFi, and any other tsDMARD treated patients, respectively. At 12M, 31.8% and 36.0% of patients in cohort A and B, respectively, reported ongoing steroid use, a reduction of 25.9% and 18.0%, respectively, from baseline. Conclusion Despite an older and more bDMARD experienced population, discontinuation rates were lower while remission was higher for those treated with BARI than those in cohort B. Discontinuation rate was consistent irrespective of BARI dose or if used in monotherapy or combination therapy. Discontinuation rates increased with number of previous b/tsDMARD in both cohorts, with numerically lower discontinuation rates at 12M for patients treated with BARI. Disclosure R. Alten: Grants/research support; R. A. has been a consultant for and/or received grant/research support from: AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB. G.R. Burmester: Consultancies; G. R. B. has been a consultant for and/or received honoraria as a speaker for: AbbVie, Eli Lilly and Company, Galapagos, Gilead, Janssen, MSD, Pfizer, Roche, and UCB. M. Matucci-Cerinic: Corporate appointments; M. M-C. has been an officer or board member for: Biogen. Consultancies; M. M-C. has been a consultant for: Behring, Chemomab, Janssen, and Pfizer. Honoraria; M. M-C. has received honoraria as a speaker for: Eli Lilly and Company, and Sandoz. Grants/research support; M. M-C. has received grant/research support from: Merck, and MSD. A. Ostor: Consultancies; A. O. has been an advisor, review panel member, and/or consultant for: Abbot, AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Gilead, Janssen, Novartis, Paradigm, Pfizer, Roche, and UCB. L. Zaremba-Pechmann: Other; L. Z-P. is a contractor for: HaaPACS GmbH. T. Treuer: Shareholder/stock ownership; T. T. is an employee and shareholder of: Eli Lilly and Company. K. Ng: Shareholder/stock ownership; K. J. N. is an employee and shareholder of: Eli Lilly and Company. J. Gerwien: Shareholder/stock ownership; J. G. is an employee and shareholder of: Eli Lilly and Company. K.A. Gibson: Consultancies; K. A. G. has been a consultant for: Janssen, and Novartis. Shareholder/stock ownership; K. A. G. is an employee and shareholder of: Eli Lilly and Company. Honoraria; K. A. G. has received honoraria as a speaker for: UCB. Grants/research support; K. A. G. has received grant/research support from: Novartis. B. Fautrel: Grants/research support; B. F. has received research grants from AbbVie, Lilly, MSD and Pfizer, and consultancy fees from AbbVie, Amgen, Biogen, BMS, Celltrion, Fresenius Kabi, Galapagos, Gilead, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Viatris. T. Sheeran (Non-Author Presenter): None.

Making the cut: How panel reviewers use evaluation devices to select applications at the European Research Council

AbstractThe European Research Council (ERC) receives many high-quality applications, but funds only a few. We analyze how members of ERC review panels assess applications in the first, highly competitive step of evaluations for ERC Starting and Consolidator Grants. Drawing on interviews with ERC panel members in different fields, we show that they adopt a set of evaluation devices that offer pragmatic and standardized ways of evaluating in a time-constrained and highly competitive setting. Through the use of evaluation devices, panel reviewers enact and generate a distinct reviewing expertise that encompasses subject-specific knowledge and knowledge about how to accomplish evaluation within a situated setting. We find that ERC panel reviewers employ four evaluation devices during the first step of ERC reviews: first, reviewers base judgments on applicants’ prior achievements (delegation devices); second, they adjust their evaluations of individual applications to the quality of a given set of applications (calibration devices); third, they combine multiple elements to assess the feasibility of proposals (articulation devices); and finally, they consider the impact of the proposed research on science and society (contribution devices). We show that the current use of these devices generates what we have termed evaluative pragmatism: a mode of reviewing that is shaped by and accommodated to the need to review many high-quality proposals in a short time period with possibly limited expert knowledge. In conclusion, we discuss how the prevalence of evaluative pragmatism in the first step of ERC panel reviews shapes candidate selection, particularly regarding human and epistemic diversity in European research.

1000. Serotype 3 pneumococci evade activation of the classical complement pathway

BackgroundComplement classical pathway (CCP) activation is the major mechanism leading to opsonophagocytic pneumococcal killing. Following immunization with 13-valent pneumococcal conjugate vaccine (PCV13), opsonophagocytic titers are lowest against serotype 3 among the 13 vaccine serotypes. Post licensure surveillance indicated early declines in serotype 3 invasive pneumococcal disease (IPD) were not sustained over time MethodsUsing flow cytometry, we measured C3 and C4 deposition on serotype 3 strains from children with IPD or nasopharyngeal [NP] carriage, and analyzed by clade. C4 deposition is an indicator of CCP, while C3 deposition is common to all complement pathways. We measured C3/C4 deposition on serotype 3 pneumococcal strains incubated with antibody depleted complement alone or with complement and the following antibodies: mouse monoclonal anti-capsular IgG or IgM, rabbit polyclonal serotype 3 antisera (IgG + IgM) [RPS3A] and RPS3A combined with anti-rabbit IgM, which blocks IgM function, leaving only polyclonal IgGResultsSerotype 3 strains demonstrated high variability in C3 binding when incubated with complement alone. RPS3A (containing both IgM+IgG) and monoclonal IgM activated CCP in all strains. Anti- serotype 3 monoclonal IgG and polyclonal IgG demonstrated absent or limited CCP activation; but activated alternative pathway in some strains. When analyzing complement deposition by clade, a lower proportion of clade II NP serotype 3 strains bound C3 when incubated with complement or monoclonal IgG, compared to clade Ia NP strains. Differences between clade Ia and II IPD strains were not apparent. ConclusionSerotype 3 strains did not demonstrate activation of the CCP in the presence IgG and varied in C3 deposition. Pneumococcal strains that evade CCP activation may be less sensitive to opsonophagocytosis. Our findings suggest a mechanism by which serotype 3 carriage and disease may persist despite immunization with conjugate vaccine containing serotype 3 polysaccharide.Disclosures Rotem Lapidot, MD MSCI, Pfizer (Consultant, Grant/Research Support, Advisor or Review Panel member) Mario Ramirez, PhD, GlaxoSmithKline (Advisor or Review Panel member)Merck Sharp & Dohme (Advisor or Review Panel member)Pfizer (Speaker’s Bureau) Ingrid L. Scully, PhD, Pfizer (Employee, Shareholder) Bradford D. Gessner, MD, MPH, Pfizer Inc. (Employee) stephen pelton, MD, Merck Vaccines (Advisor or Review Panel member, Research Grant or Support)Pfizer, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support)Sanofi pasteur (Advisor or Review Panel member, Research Grant or Support, DSMB)Seqirus (Consultant)

1187. Neurodevelopmental Outcomes of Children with Congenital Cytomegalovirus (cCMV) Infection: Does Antiviral Treatment Matter?

BackgroundcCMV infection is a major contributor to childhood neurologic and cognitive disabilities including sensorineural hearing loss (SNHL). Neonatal treatment with ganciclovir/valganciclovir improves hearing outcomes, but its impact on neurodevelopmental outcomes remains an important knowledge gap. We describe the neurodevelopmental outcomes of children with cCMV infection and evaluate the effect of neonatal antiviral therapy on outcomes. MethodsSince 2013, infants with cCMV infection referred to Nationwide Children’s Hospital’s NEO-ID Clinic have had a complete evaluation at diagnosis as well as follow-up neurodevelopmental assessments. Pertinent demographic, clinical, laboratory, radiographic, and follow-up data were obtained and managed using REDCap. Neurodevelopmental assessments were performed using Bayley Scales of Infant and Toddler Development (BSID) III/IV (cognitive, language, motor domains) at ~ 24 months of age. The Gross Motor Function Classification System was used to classify functional motor impairment. Neurodevelopmental outcomes were compared by receipt of antiviral therapy in early infancy. Results95 infants (mean ± SD; gestational age 35 ± 5 wk, birth weight 2121 ± 948 g; Table 1) with cCMV infection had follow-up neurodevelopmental assessments. 62% had central nervous system involvement, 37% had SNHL, 23% developed cerebral palsy (CP), and 6% were diagnosed with autism spectrum disorder. The majority had normal BSID scores (≥ 85) in cognitive and motor domains (65% and 54%, respectively) while 48% had normal scores in the language domain. 35% had severe impairment (< 70) in ≥ 1 domain (Table 2). 9 children had clinically inapparent cCMV infection; 2 (22%) had abnormalities on BSID testing (1, cognitive score: 80; 1, cognitive, language, and motor scores: 65, 68, 73, respectively). 11 (12%) children, including 6 who received antiviral therapy, had severe neurodevelopmental impairment, with CP and severe (< 70) BSID scores in both the cognitive and motor domains. Table 1. Demographic and Clinical Characteristics of 95 Children with Congenital CMV Infection by Receipt of Antiviral Treatment Table 2. Neurodevelopmental Outcomes Based on Testing with the Bayley Scales of Infant and Toddler Development (BSID) III/IV ConclusionA substantial proportion of children with cCMV infection had moderate (29%) or severe (33%) neurodevelopmental impairment, CP, or autism spectrum disorder, irrespective of antiviral treatment. Urgency exists for antenatal preventive strategies and vaccine development.Disclosures Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member)

79. Children with COVID-19 Demonstrate Distinct Serum Cytokines Profiles According to Clinical Presentations

BackgroundAlmost 4 million children have tested positive for Coronavirus Disease 2019 (COVID-19) as of June 3 2021, representing 14% of all cases in USA. Children present with diverse clinical findings including the multisystem inflammatory syndrome in children (MIS-C). In this study, we measured serum cytokine concentrations in children with COVID-19 to identify differences in immune profiles according to clinical presentations. MethodsA total of 133 children 0-21 years of age with COVID-19 were enrolled at Nationwide Children’s Hospital, in Columbus, Ohio. Nasopharyngeal swab RT-PCR testing was used for SARS-CoV-2 detection and quantification. Clinical and laboratory information were obtained, and blood samples were collected for measurement of cytokines with a 92-plex inflammation assay (Olink). Normalized cytokine expression levels in patients were compared with serum samples from 66 pre-pandemic age-matched healthy controls.ResultsCOVID-19 children included: 1) those identified by universal screening (n=47); 2) moderate disease (ward; n=48); 3) severe disease (PICU; n=20); 4) MIS-C (n=18). Children identified by universal screening were hospitalized for trauma, appendicitis or new onset diabetes among others. Children with symptomatic COVID-19 had significantly higher SARS-CoV-2 viral loads than children with MIS-C or those identified via universal screening. Concentrations of interferon (IFN) related cytokines (IFNg, CXCL9, CXCL10, CXCL11), interleukins (IL6, IL8, IL10, IL17A, IL18, IL24) and other inflammatory cytokines (TGF, TNF, VEGF, MCP, CD40) were significantly increased in children with acute COVID-19 and MIS-C compared with children identified by universal screening and healthy controls. These cytokines were positively correlated with C-reactive protein, D-dimer and disease severity in COVID-19, but negatively correlated with viral loads (Fig 1). MIS-C showed stronger inflammatory response than acute COVID-19 (Fig 2). Correlation of Age-adjusted cytokine expression values with viral load, disease severity, CRP and D-dimer. Pearson correlation coefficient is shown for each pair. Red: positive correlation; blue: negative correlationCytokines that differentiate MIS-C from acute COVID-19 Heatmap shows the differential expressed cytokines between MIS-C and acute severe COVID-19 (padj<0.05, FC>2). The age-adjusted expression values are normalized the median of healthy controls. Red: up-regulation, blue: down-regulation.ConclusionWe identified three cytokine clusters in children with COVID-19 according to clinical presentations. Correlations of serum cytokines with clinical/laboratory parameters could be used to identify potential biomarkers associated with disease severity in COVID-19Disclosures Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member) Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member)

81. SARS-CoV-2 RNAemia and Disease Severity in Pediatric Coronavirus Disease 2019 (COVID-19)

Abstract Background Children with COVID-19 may develop severe disease. In hospitalized adults, detection of plasma SARS-CoV-2 RNAemia ranges from 19% to 42% and has been associated with worse clinical outcomes. A similar association in children remains unexplored. We determined the frequency of SARS-CoV-2 RNAemia in children hospitalized with COVID-19 and evaluated its potential association with severe disease. Methods Single center prospective study that enrolled hospitalized children and adolescents ≤21 years old with COVID-19 from March 2020-April 2021 at Nationwide Children’s Hospital, Columbus, OH. Nasopharyngeal (NP) and blood samples were obtained and SARS-CoV-2 RNA was quantified using a real time PCR assay targeting the N1 gene. Pertinent demographic, clinical, laboratory, and outcome data were evaluated. Results We enrolled a convenience sample of 103 hospitalized children (median age, 9 years; range, 3 days-21 years) who had confirmed SARS-CoV-2 infection and both NP and blood samples obtained (Table 1). Overall, 27 (26%) patients with COVID-19 had SARS-CoV-2 RNAemia. Compared with patients who had undetectable RNAemia, those with SARS-CoV-2 RNAemia had significantly higher nasopharyngeal RNA loads (8.1 vs. 4.9 log10 copies/mL; p=0.0006), fever (78 vs 54%; p=0.02), receipt of supplemental oxygen (37% vs 14%; p=0.02), and treatment with anti-COVID-19 medications (30% vs 12%; p=0.04). In addition, patients with SARS-CoV-2 RNAemia were more likely to require intensive care (40%% vs. 20%, p= 0.04) and had longer hospitalization (2.56 vs 2.15 days; p=0.03). There were no COVID-19 related deaths. Table 1. Demographic, clinical, laboratory and virology characteristics of study patients Conclusion The frequency of SARS-CoV-2 RNAemia in pediatric patients was 26% and its finding was associated with worse clinical in-hospital outcomes, similar to that reported in adults. Testing for SARS-CoV-2 RNAemia in children may help identify those who could benefit from more intensive supportive care as well as antiviral and anti-inflammatory medications. Disclosures Octavio Ramilo, MD, Adagio (Consultant)Bill &amp; Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member)

999. Nasal Mucosal Cytokines: Potential Biomarkers for Pediatric Pneumonia Severity and Etiology

BackgroundCommunity acquired pneumonia (CAP) is a leading cause of mortality in children < 5 years, but our understanding of disease pathogenesis remains limited. The objective of this study was to define the local host immune response in the respiratory tract by measuring nasal mucosal cytokine (NMC) concentrations (conc.). We hypothesized that NMC represent a potential biomarker to help assessing disease severity and pathogen classification.MethodsWe leveraged nasopharyngeal (NP) samples and clinical data from an observational multicenter study [Children’s Hospital’s Initiative for Research in Pneumonia (CHIRP)] conducted between 2015 and 2018. We measured conc. of 92 NMC using the Olink immunoassay. NMC conc. were compared by severity-defined by need for hospitalization, mild (outpatient) and severe (inpatient), and by identified pathogen using Mann-Whitney U test.ResultsThis substudy included 182 children with CAP (mild=61; severe=121) and 30 healthy controls (HC). The pathogens identified included: 101 viruses; 32 bacteria (pyogenic=10; atypical=22); 12 with >1 pathogen; and 37 with no pathogen. Children with severe CAP had greater CCL23 and MCP-3 conc. than those with mild disease (p=0.012; p=0.011 respectively). When comparing NMC profiles of children with CAP of viral and bacterial etiology, the viral group had greater conc. of proinflammatory cytokines IL-6 and TNF, (p=0.0002; p=0.0098 respectively). Further subgroup analysis showed that CAP secondary to influenza virus had greater conc. of IL-6, TNF, and antiviral INF-γ and IP-10 compared with CAP caused by pyogenic bacteria. IL-6 and MCP1-4 were significantly increased in the influenza group compared to the atypical bacteria group. Quantification of NMC in children with CAP based on disease severity NMCnasal mucosal cytokine; CAP: community acquired pneumonia; NPX: normalized protein expression, arbitrary unit used in Olink assay that is log 2 scale. Mann-Whitney test was used to determine differences between mild and severe pneumoniaQuantification of NMC in children with CAP based on pathogen classification NMC: nasal mucosal cytokine; CAP: community acquired pneumonia; NPX: normalized protein expression, arbitrary unit used in Olink assay that is log 2 scale. Mann-Whitney test was used to determine differences between bacterial CAP and viral CAP.ConclusionChildren with severe CAP had higher monocyte chemoattractant NMC conc. than children with mild disease. Children with viral CAP, particularly influenza, had a more robust mucosal response including both proinflammatory and antiviral NMC than children with bacterial CAP. These findings show differences in NMC conc. based on etiology and disease severity. Further studies are needed to determine whether NMC are reliable predictive biomarkers of CAP etiology and severity.Disclosures Lilliam Ambroggio, PhD, MPH, Pfizer Inc (Grant/Research Support) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member) Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member)

80. Heme Oxygenase-1 Gene promoter and associations with inflammation and subclinical vascular disease in Ugandan adolescents with and without HIV

Abstract Background Heme oxygenase-1 (HO-1) is a cytoprotective enzyme with potent anti-inflammatory, and anti-oxidant effects. The HO-1 response is modulated by functional polymorphisms (a dinucleotide (GT)n repeat length variation) in the HO-1 gene promoter region which have been associated with cardiovascular disease (CVD) susceptibility in adults. HO-1 polymorphisms and their associations with markers of inflammation and CVD in Ugandan adolescents with (HIV+) and without HIV (HIV-) have not been investigated. Methods We included 177 children (92 HIV+, 85 HIV-) enrolled in an ongoing observational cohort study at the Joint Clinical Research Center, Kampala, Uganda. All HIV+ participants were on ART. HO-1 (GT)n allele genotypes were determined by PCR of the (GT)n repeat region followed by fragment size determination on a capillary sequencer in DNA extracted from blood samples. Allele designations were assigned by number of (GT)n repeats: S &amp;lt; 27, M 27-34, or L &amp;gt; 34 repeats. We measured mean common carotid artery intima-media thickness (IMT) as a marker of CVD, markers of systemic inflammation (hsCRP, IL6, sTNFRI), monocyte activation (sCD14 and sCD163), and T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+) , oxidized lipids, markers of gut integrity and fungal translocation (BDG). Results Median age (IQR) was 13 (11, 14), 44% were females, 86% had viral load &amp;lt; 20 copies/mL. 19% had a short allele genotype, 37% had a medium allele genotype and 44% had a long allele genotype (Figure). The shortest and longest allele length correlated with lower IMT in HIV- only (r=-0.36 and -0.30, respectively, p≤ 0.01 for both). Among biomarkers, only the medium allele correlated with oxidized lipids in HIV+ and with hsCRP and BDG in HIV- (p≤ 0.05). After adjusting for age, sex, and BMI, the presence of a long allele was associated with lower IMT. This was no longer significant after adjusting for markers of inflammation or oxidized lipids (Table). Heme Oxygenase-1 genotype allele length frequency in Ugandan cohort of HIV+ and HIV- youth 1: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2) and HIV status (positive vs negative) 2: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), sCD14 (pg/mL) and HIV status (positive vs negative) 3: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), high sensitivity C reactive protein (ng/mL) and HIV status (positive vs negative) 4: Models are adjusted for age (years), sex (male vs female), BMI (kg/m2), oxidized lipids and HIV status (positive vs negative) Conclusion These findings underscore the potential of the HO pathways in modulating future risk for CVD in adolescents through inflammation. HIV status in this setting, likely influences the associations with the genotype with the risk of CVD. Further studies to validate our findings in this population are required. Disclosures Grace A. McComsey, MD, Gilead (Consultant, Advisor or Review Panel member)Janssen (Consultant, Advisor or Review Panel member)Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Redhill (Research Grant or Support)Roche (Grant/Research Support)Tetraphase, Astellas (Research Grant or Support)Theratechnologies (Consultant)Vanda (Grant/Research Support)ViiV/GSK (Scientific Research Study Investigator, Advisor or Review Panel member)

1186. Increased Respiratory Syncytial Virus (RSV) Viral Replication Leads to Increased Cytokine Production and Polarized Interferon Response in Infant Mucosal Epithelium

BackgroundRSV is the most frequent etiology of pediatric lower respiratory tract infection. Most children hospitalized for RSV are previously healthy without known risk factors. Children with mild disease managed as outpatients (OP) have higher viral loads than those hospitalized with severe disease. OP children have higher concentrations of the mucosal interferon (IFN), IFNλ2/3, and IP-10, but no differences in IFNλ1. We examined how RSV replication impacts cytokine production kinetics in the nasal mucosa.MethodsPrimary infant human nasal epithelial (iHNE) cells were collected from nasopharyngeal swabs and cultured on an air-liquid interface. Cultures were infected with 0.1 or 0.001 multiplicity of infection (MOI) of RSV-A, or mock infected. Concentrations of IFN-related (IFNα2, β, γ, λ1, λ2/3, and IP-10) and inflammatory (IL-1β, -6, -12, and TNFα) cytokines secreted to the apical and basolateral surfaces were quantified via immunoassay. Kinetics according to viral inocula were compared by ANOVA with Dunn post-hoc testing of the area under the curve (AUC) for each cytokine. Peak concentrations were compared according to MOI and secretion surface by 2-way ANOVA.ResultsAUC of IFNs in both surfaces of RSV infected cells were significantly higher than those of mock infected. The 0.1 MOI RSV inoculum resulted in significantly higher AUCs for all IFN cytokines on both surfaces than the 0.001 MOI. Peak IFNλ1 concentrations were higher on the apical than basolateral side; peak IFNλ2/3 concentrations were higher on the basolateral side than apical. AUCs of inflammatory cytokines in RSV infection were significantly higher on the basolateral, but not apical, surfaces than mock; all basolateral inflammatory cytokines were higher in the 0.1 MOI than the 0.001 MOI.ConclusionHigher RSV inoculum induces higher concentrations of IFN-related cytokines on both sides of epithelial cells, and higher concentrations of inflammatory cytokines on the basolateral side. Differential secretion of IFNλ1 and IFNλ2/3 to the apical and basolateral surfaces suggests they may play different roles in immune response during RSV infection. These data support viral replication as an important factor influencing RSV pathogenesis and severity through cytokine production.Disclosures Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member) Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member)

204. Mucosal Cytokine Profiles in Children with COVID-19

BackgroundThe mechanisms associated with COVID-19 in children are not well understood. We sought to define the differences in nasopharyngeal (NP) cytokine profiles according to clinical presentation in children with COVID-19. MethodsSingle-center, prospective study in 137 children and adolescents < 21 years of age hospitalized with COVID-19, and 35 age, sex and race matched pre-pandemic (2016-2019) healthy controls. Children with COVID-19 were categorized according to their clinical presentation in: COVID-19-symptomatic; COVID-19-screening, and multisystem inflammatory syndrome (MIS-C). NP swabs were obtained within 24 hours of admission to measure SARS-CoV-2 loads by rt-PCR, and a 92-cytokine panel. Unsupervised and supervised analysis adjusted for multiple comparisons were performed.ResultsFrom 3/2020 to 1/2021, we enrolled 76 COVID-19-symptomatic children (3.5 [0.2-15.75] years); 45 COVID-19-screening (11.1 [4.2-16.1] years), and 16 MIS-C (11.2 [5.9-14.6] years). Median NP SARS-CoV-2 loads were higher in COVID-19-symptomatic versus screening and MIS-C (6.8 vs 3.5 vs 2.82 log10 copies/mL; p< 0.001). Statistical group comparisons identified 15 cytokines that consistently differed between groups and were clustered in three functional categories: (1) antiviral/regulatory, (2) pro-inflammatory/chemotactic, and (3) a combination of (1) and (2); (Fig 1). All 15 cytokines were higher in COVID-19-symptomatic versus controls (p< 0.05). Similarly, and except for TNF, CCL3, CCL4 and CCL23, which were comparable in COVID-19-symptomatic and screening patients, the remaining cytokines were higher in symptomatic children (p< 0.05). PDL-1 (p=0.01) and CCL3 (p=0.03) were the only cytokines significantly decreased in children with MIS-C versus symptomatic COVID-19 children. The 15 cytokines identified by multiple comparisons were correlated using Person’s in R software. Red reflects a positive correlation and blue a negative correlation with the intensity of the color indicating the strength of the association.ConclusionChildren with symptomatic COVID-19 demonstrated higher viral loads and greater mucosal cytokines concentrations than those identified via screening, whereas in MIS-C concentrations of regulatory cytokines were decreased. Simultaneous evaluation of viral loads and mucosal immune responses using non-invasive sampling could aid with the stratification of children and adolescents with COVID-19 in the clinical setting. DisclosuresOctavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member).

1193. Mucosal Antibody Responses to Respiratory Syncytial Virus (RSV) in Infants and Young Children

Abstract Background The burden associated with RSV infection is substantial. Although RSV initially infects the upper respiratory tract, there is limited information of the mucosal concentrations of antibodies (Abs) directed to RSV specific proteins and whether patient’s age and disease severity influence production of mucosal Abs. Methods From 2017 to2019 we enrolled previously healthy children &amp;lt; 2 years of age hospitalized with RSV infection and obtained acute and convalescent (day; D30) nasopharyngeal (NP) samples to measure preF and postF specific IgG and IgA Abs by ELISA. Demographic and clinical data were collected and analyzed according to Abs responses. Results We enrolled 77 children (median [IQR] age: 2.8 [1.5-5.2] months; 49 % females) within the first 24 hours of hospitalization. Of those 25 (33%) patients required PICU care. A significant increase in convalescent IgG preF Abs titers was detected in 62 (81%) children, while IgA preF titers significantly increased in all but one child on D30. The magnitude of the increase was 56-fold higher for preF IgA versus preF IgG (p&amp;lt; 0.0001). PostF IgG and IgA titers were also increased on D30 but at significant lower levels. Infants &amp;lt; 3 months of age compared with those &amp;gt;3-24 months had significantly higher baseline preF and postF IgG Abs titers (p &amp;lt; 0.001) but not IgA antibodies. D30 preF and post F IgG titers were higher in children &amp;gt; 6 months of age (p &amp;lt; 0.0001) but only preF titers fold change significantly correlated with age (r=0.4, p&amp;lt; 0.0001). These correlations were not identified with IgA preF antibodies. There were no statistical differences in antibody titers at baseline and on D30 according to breastfeeding, and disease severity as defined by the need for PICU care. Conclusion Children hospitalized with RSV infection demonstrated significantly increased titers of mucosal preF and post F IgG and IgA specific Abs in convalescent samples. Baseline IgG Abs where higher in younger infants, which likely reflects maternally acquired antibodies. Age significantly correlated with Abs production, suggesting a more robust immune response in older children. Disclosures Mark E. Peeples, PhD, Janssen (Research Grant or Support)Pfizer (Research Grant or Support) Octavio Ramilo, MD, Adagio (Consultant)Bill &amp; Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member)

82. Blood Gene Expression Profiles in Neonates with Herpes Simplex Virus (HSV) Infection

Abstract Background Neonatal HSV infection is associated with significant morbidity and mortality. Neonates with HSV infection can present with skin, eye, and mouth (SEM), central nervous system disease (CNS), and disseminated disease (DIS). We hypothesize that host immune responses may contribute to differences in disease presentation and outcomes. To address this knowledge gap, we analyzed host transcriptional immune profiles of neonates with HSV infection. Methods Infants &amp;lt; 6 weeks of age (24 (86%) &amp;lt; 4 weeks; 4 (14%) 4-6 weeks old) with neonatal HSV, and healthy infant controls (HC) were enrolled at Children’s Medical Center (Dallas, TX), and Nationwide Children’s Hospital (Columbus, OH) from 2007-2018. Whole blood samples were analyzed by RNA-seq. Modular analyses were performed to identify the immune pathways that were activated or suppressed according to each HSV disease category. Results Of the 28 infants with HSV infection, 9 had SEM (median [IQR] age: 14 [14-28] days), 10 CNS (age: 18 [15-29] days), and 9 DIS (age: 10 [7-10] days). Three infants with DIS died within 5 days of diagnosis. Statistical group comparisons between 13 HC and 18 infants with HSV disease (training set) identified 1,322 differentially expressed genes (neonatal HSV biosignature). This biosignature was validated in the remaining 10 infants with HSV disease (test set), and was characterized by significant overexpression of interferon (INF), inflammation, neutrophils, and monocyte genes and under-expression of T-cell genes. Further analysis according to HSV disease category confirmed overexpression of neutrophil and inflammation genes in infants with SEM, CNS and DIS (Fig 1). On the other hand, overexpression of INF and plasma cell genes, and further suppression of monocytes, cytotoxic/NK cells, and T-cell genes were only evident in children with DIS. Fig 1: Modular immune pathways according to HSV disease category Modules are groups of genes that shared a similar function. Each dot represents a transcriptional module with red indicating overexpression and blue underexpression in relation to healthy controls. The number and color intensity on the dot indicate the percentage of differentially expressed transcripts within a module. SEM: skin, eye mouth; CNS: central nervous system; DIS: disseminated HSV disease. Conclusion Transcriptional profiles of infants with HSV infection exhibited marked activation of the innate immune response irrespective of disease classification. Children with DIS showed more profound dysregulation and suppression of cellular immune responses. Transcriptional profiling may aid unravel mechanisms associated with clinical outcomes in neonatal HSV and inform future therapeutic and preventive strategies. Disclosures Octavio Ramilo, MD, Adagio (Consultant)Bill &amp; Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member)

105. Impact of a Multiplex Polymerase Chain Reaction Panel on Duration of Empiric Antibiotic Therapy in Suspected Bacterial Meningitis

BackgroundMultiplex polymerase chain reaction (PCR) panels allow for rapid detection or exclusion of pathogens causing community-acquired meningitis and encephalitis (ME). However, the clinical impact of rapid multiplex PCR ME panel results on the duration of empiric antibiotic therapy is not well characterized.MethodsWe performed a retrospective pre-post study to evaluate the implementation of the FilmArray ME panel (BioFire Diagnostics, LLC) for diagnosis of bacterial meningitis at our institution. We included adults who presented with suspected bacterial meningitis, received empiric antibiotic therapy, and underwent cerebrospinal fluid microbiological testing in the emergency department. The primary outcome was duration of empiric antibiotic therapy. A bivariable analysis that compared baseline demographics, clinical characteristics, and study outcomes between the pre-ME panel and post-ME panel periods was performed using Mann-Whitney tests, chi-squared tests, or Fisher’s exact tests. Time-to-event analysis used the Kaplan-Meier method and log-rank statistics.ResultsIn the pre-ME panel period, the positive detection rate of bacterial pathogens was 2.2% (3/137) by cerebrospinal fluid culture and 4.3% (3/69) in the post-ME panel period. Table 1 shows baseline characteristics of patients. Compared to the pre-ME panel period, there were significant reductions in the post-ME panel period for the duration of empiric antibiotic therapy (median 34.7 h, IQR 8.5–61.7, vs. 12.3 h, IQR 3.3–40.0, P=0.01), time to targeted therapy (59.3 h, IQR 36.5–74.6, vs 7.02 h, IQR 0.9–12.4, P< 0.001), and hospital length of stay (4 d, IQR 2–7, vs. 3 d, IQR 1–5, P=0.03), as shown in Table 2. There was also significant reduction in time to discontinuation or de-escalation of empiric antibiotic therapy (P=0.049) as shown in Figure 1.Table 1. Baseline characteristics for patients with suspected bacterial meningitis Table 2. Antimicrobial use and hospitalization outcomes Compared to the pre-ME panel period, there were significant reductions in the post-ME panel period for the duration of empiric antibiotic therapy (P=0.01), time to targeted therapy (P<0.001), and hospital length of stay (P=0.03).Figure 1. Probability of Empiric Antibiotic Therapy Between Pre- and Post-ME Panel Periods Kaplan-Meier analysis of the time from initiation of empiric antibiotic therapy to discontinuation or de-escalation of empiric antibiotic therapy between the pre- and post-ME panel periods. P value from log-rank test=0.049 (n=206). There was a significant difference in the time to discontinuation or de-escalation of empiric antibiotic therapy between the groups (sex- and immunosuppressant use-adjusted hazard ratio, 1.46 [95% confidence interval, 1.08–1.97]; P=0.01).ConclusionThe implementation of the FilmArray ME panel for suspected bacterial meningitis appears to reduce the duration of empiric antibiotic therapy, time to targeted therapy, and hospital length of stay compared to traditional culture-based microbiological testing methods.Disclosures Justin J. Choi, MD, Allergan (Consultant, Grant/Research Support)Roche (Consultant, Grant/Research Support) Lars Westblade, PhD, Accelerate Diagnostics Inc (Grant/Research Support)BioFire Diagnostics (Grant/Research Support)Hardy Diagnostics (Grant/Research Support)Roche (Consultant, Advisor or Review Panel member)Shionogi Inc (Advisor or Review Panel member)Talis Biomedical (Advisor or Review Panel member) Marshall J. Glesby, MD, Enzychem (Consultant)Gilead (Grant/Research Support)ReAlta Life Sciences (Consultant)Regeneron (Consultant, Grant/Research Support)Sobi (Consultant)Springer (Other Financial or Material Support, Royalties)UpToDate (Other Financial or Material Support, Royalties)

18. An Easy-to-Implement Clinical-Trial Frailty Index Based on Accumulation of Deficits: Validation in Zoster Clinical Trials

BackgroundThe impact of frailty on the efficacy and safety of vaccines and therapeutic interventions is increasingly recognized, yet assessment of frailty in clinical trials is often considered logistically challenging. We developed the retrospective Clinical Trial Frailty Index (CT-FI), using baseline medical history and patient reported outcomes collected via standard instruments (Short Form Survey-36 and Euro Quality of Life-5 Dimension) in two clinical trials of the adjuvanted recombinant zoster vaccine (RZV, ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]). This post-hoc analysis aimed to show that CT-FI is a robust measure that may be used in any analysis where sufficient patient data has been collected in a clinical trial.MethodsItems included in the CT-FI were scored from 0 to 1, summed for each participant and divided by the total number of potential deficits. CT-FI was validated using descriptive methods verifying distribution and age- and sex-associations in relation to established FI characteristics, Cox regressions in relation to fatal outcomes hypothetically related to frailty, and re-sampling methods (Jackknife and Bootstrap procedures) within the FI to demonstrate robustness to inclusion/exclusion of specific individual variables.ResultsThe CT-FI distribution followed a gamma distribution with a range of 0 to 0.695; the distribution shifted to the right with age. The age-related slope of mean deficit accumulation per year increased with chronological age and was higher for women than men. The rate of mean deficit accumulation was 0.0025 for women vs 0.0016 for men < 70 years of age, and this increased to 0.0058 for women vs 0.0047 for men ≥70 years of age. In univariate and multivariate Cox regression survival analyses, FI, chronological age and sex were significant predictor factors for mortality. The Jackknife and Bootstrap re-sampling methods showed that the performance of CT-FI was not sensitive to inclusion/exclusion of specific individual or groups of variables, demonstrating the robustness of this methodology. ConclusionThe current analysis validates that CT-FI, an easy-to-implement FI, is a robust method which allows retrospective/prospective evaluation of clinical outcomes by frailty status in clinical trials.Disclosures Melissa K. Andrew, MD, PhD, GSK (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Sanofi (Consultant, Grant/Research Support, Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Sean Matthews, MSc, GSK (Independent Contractor) Joon Hyung Kim, MD, GSK group of companies (Employee, Shareholder) Megan Riley, PhD, GSK group of companies (Employee, Shareholder) Desmond Curran, PhD, The GSK group of companies (Employee, Shareholder)

33. Evaluation of Rural-Urban Differences in Hospitalization and Mortality Rates for US COVID-19 Patients in the United States

BackgroundRural communities are among the most vulnerable and resource-scarce populations in the United States. Rural data is rarely centralized, precluding comparability across regions, and no significant studies have studied this population at scale. The purpose of this study is to present findings from the National COVID Cohort Collaborative (N3C) to provide insight into future research and highlight the urgent need to address health disparities in rural populations.N3C Patient Distribution This figure shows the geospatial distribution of the N3C COVID-19 positive population. N3C contains data from 55 data contributors from across the United States, 40 of whom include sufficient location information to map by ZIP Code centroid spatially. Of those sites, we selected 27 whose data met our minimum robustness qualifications for inclusion in our study. This bubble map is to scale with larger bubbles representing more patients. A. shows all N3C patients. B. shows only urban N3C distribution. C. shows the urban-adjacent rural patient distribution. D. shows the nonurban-adjacent rural patient distribution, representing the most isolated patients in N3C.MethodsThis retrospective cohort of 573,018 patients from 27 hospital systems presenting with COVID-19 between January 2020 and March 2021, of whom 117,897 were admitted (see Data Analysis Plan diagram for inclusion/exclusion criteria), analyzes outcomes and 30-day survival for the hospitalized population by the degree of rurality.Multivariate Cox regression analysis and mixed-effects models were used to estimate the association between rurality, hospitalization, and all-cause mortality, controlling for major risk factors associated with rural-urban health discrepancies and differences in health system outcomes. The difference in distribution by rurality is described as well as supplemented by population-level statistics to confirm representativeness.Data Analysis Plan This data analysis plan includes an overview of study inclusion and exclusion criteria, the matrix for data robustness to determine potential sites to include, and our covariate selection, model building, and residual testing strategy.ResultsThis study demonstrates a significant difference between hospital admissions and outcomes in urban versus urban-adjacent rural (UAR) and nonurban-adjacent rural (NAR) lines. Hospital admissions for UAR (OR 1.41, p< 0.001, 95% CI: 1.37 – 1.45) and NAR (OR 1.42, p< 0.001, 95% CI: 1.35 – 1.50) were significantly higher than their urban counterparts. Similar distributions were present for all-cause mortality for UAR (OR 1.39, p< 0.001, 95% CI: 1.30 – 1.49) and NAR (OR 1.38, p< 0.001, 95% CI: 1.22 – 1.55) compared to urban populations. These associations persisted despite adjustments for significant differences in BMI, Charlson Comorbidity index Score, gender, age, and the quarter of diagnosis for COVID-19.Baseline Characteristics Hospitalized COVID-19 Positive Population by Rurality Category, January 2020 – March 2021 Survival Curves in Hospitalized Patients Over 30 Days from Day of Admission This figure shows a survival plot of COVID-19 positive hospitalized patients in N3C by rural category (A), Charlson Comorbidity Index (B), Quarter of Diagnosis (C), and Age Group (D) from hospital admission through day 30. Events were censored at day 30 based on the incidence of death or transfer to hospice care. These four factors had the highest predictive power of the covariates evaluated in this study.Unadjusted and Adjusted Odds Ratios for Hospitalization and All-Cause Mortality by Rural Category, January 2020 – March 2021 This figure shows the adjusted and unadjusted odds ratios for being hospitalized or dying after hospitalization for the COVID-19 positive population in N3C. Risk is similar between adjusted and unadjusted models, suggesting a real impact of rurality on all-cause mortality. A shows the unadjusted odds ratios for admission to the hospital after a positive COVID-19 diagnosis for all N3C patients. B shows the unadjusted odds ratios for all-cause mortality at any point after hospitalization for COVID-19 positive patients. C shows the adjusted odds ratios for being admitted to the hospital after a positive COVID-19 diagnosis for all N3C patients. D shows the adjusted odds ratios for all-cause mortality for all-cause mortality at any point after hospitalization for COVID-19 positive patients. Adjusted models include adjustments for gender, race, ethnicity, BMI, age, Charlson Comorbidity Index (CCI) composite score, rurality, and quarter of diagnosis. The data provider is included as a random effect in all models.ConclusionIn N3C, we found that hospitalizations and all-cause mortality were greater among rural populations when compared to urban populations after adjustment for several factors, including age and co-morbidities. This study also identified key demographic and clinical disparities among rural patients that require further investigation.Disclosures Sally L. Hodder, M.D., Gilead (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Viiv Healthcare (Grant/Research Support, Advisor or Review Panel member)

1298. Validation of Local Pseudomonas aeruginosa Risk Factors in Patients with Community-Onset Bacterial Pneumonia

BackgroundClinical guidelines for community-acquired pneumonia (CAP) encourage validation of local risk factors for multidrug-resistant organisms. This study aimed to validate previously derived, local risk factors for Pseudomonas aeruginosa in patients with community-onset bacterial pneumonia at Prisma Health-Midlands’ hospitals. MethodsIn this retrospective, observational cohort study, adult patients hospitalized with pneumonia MS-DRG codes from January 1, 2017 to March 31, 2020 were randomly screened. Enrolled subjects were admitted to 1 of 3 Prisma Health-Midlands’ hospitals with: diagnosis of pneumonia; receipt of inpatient antibiotics within 48 hours of symptom onset; receipt of over 48 hours of antibiotic therapy; and a causative bacterial pathogen identified via respiratory or blood culture, urinary antigen, or respiratory multiplex PCR panel. Performance of the locally derived score was compared to the Drug Resistance in Pneumonia (DRIP) Score, IDSA 2019 CAP guideline risk factors, and healthcare-associated pneumonia (HCAP) risk factors. Endpoints included sensitivity, specificity, positive and negative predictive value, overall accuracy, and over- and undertreatment rates. Overall accuracy was defined as a case in which the gram-negative antibiotic coverage recommended by the scoring schema would have been appropriate for the identified organism, i.e. neither overtreatment (overly broad-spectrum) nor undertreatment (inadequate spectrum). ResultsOf 713 patients screened, 36 patients met criteria and were enrolled. The most common bacterial pathogens identified were Pseudomonas aeruginosa (n = 10, 27.8%) and Streptococcus pneumoniae (n = 10, 27.8%). Performance characteristics for each scoring schema are summarized in Table 1.Table 1. Performance characteristics of risk scores predicting for Pseudomonas aeruginosa community-onset bacterial pneumonia. MDRO=multidrug-resistant organism; DRIP=Drug Resistance in Pneumonia Score; IDSA=Infectious Diseases Society of America 2019 Community-Acquired Pneumonia Guideline risk factors ; HCAP=healthcare-associated pneumonia risk factorsConclusionCompared to DRIP or IDSA 2019 CAP risk scores, the local risk score performed well at ruling out resistant gram-negatives given its higher specificity and lower overtreatment rate; yet, it did not perform as well at ruling in resistant gram-negatives given a lower sensitivity and undertreatment rate. All scores performed better than HCAP risk factors. Data from this study will be utilized to further refine the local risk score algorithm. Disclosures P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member) Hana Winders, PharmD, BCIDP, biomerieux (Grant/Research Support) Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder)