New report evaluates the challenges that women still face in the construction sector

Civil engineer Joana Palha of business consultancy Ayming introduces a report her firm published last year on the challenges still facing women in construction. Contributors included former Civil Engineering editorial panel member Liz King of Mott MacDonald.

1340. The Burden of Influenza and Rhinovirus Among Hospitalized Adults Post the COVID-19 Pandemic

Background Acute respiratory tract infections (ARIs) are a significant cause of morbidity in adults. Influenza is associated with about 490,600 hospitalizations and 34,200 deaths in the US in the 2018-2019 season. The burden of rhinovirus among adults hospitalized with ARI is less well known. We compared the burden of influenza and rhinovirus from 2 consecutive winter respiratory viral seasons in hospitalized adults and healthy controls pre-COVID-19 and one season mid-COVID-19 to determine the impact of rhinovirus as a pathogen. Methods From Oct 2018 to Apr 2021, prospective surveillance of adults ≥50 years old admitted with ARI or COPD/CHF exacerbations at any age was conducted at two Atlanta hospitals. Adults were eligible if they lived within an eight-county region around Atlanta and if their symptom duration was < 14 days. In the seasons from Oct 2018 to Mar 2020, asymptomatic adults ≥50 years old were enrolled as controls. Standard of care test results were included and those enrolled contributed nasopharyngeal swabs that were tested for respiratory pathogens using BioFire® FilmArray® Respiratory Viral Panel (RVP). Results During the first two seasons, 1566 hospitalized adults were enrolled. Rhinovirus was detected in 7.5% (118) and influenza was detected in 7.7% (121). Rhinovirus was also detected in 2.2% of 466 healthy adult controls while influenza was detected in 0%. During Season 3, the peak of the COVID-19 pandemic, influenza declined to 0% of ARI hospitalizations. Rhinovirus also declined (p=0.01) but still accounted for 5.1% of all ARIs screened (Figure 1). Rhinovirus was detected at a greater rate in Season 3 than in asymptomatic controls in the first 2 seasons (p=0.008). In the first two seasons, Influenza was detected in 8.6% (24/276) of those admitted to the ICU. Rhinovirus was detected in 6.1% (17/276) of those admitted to the ICU but declined to 3.1% (8/258) in Season 3. Figure 1. Percent Positive Cases of Influenza and Rhinovirus between Season 1&2 (hospitalized and healthy controls) vs Season 3 (hospitalized) Conclusion Dramatic declines occurred in influenza in adults hospitalized with ARI, CHF, or COPD in Atlanta during the COVID-19 pandemic and with enhanced public health measures. Although rhinovirus declined during the COVID-19 pandemic, it continued to be identified at a rate higher than in historical controls. Additional data are needed to understand the role of rhinovirus in adult ARI, CHF, and COPD exacerbations. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory; Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

LB1. Remdesivir for the Treatment of High-Risk Non-Hospitalized Individuals With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial

Background Remdesivir (RDV) is a potent nucleotide prodrug inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase that has demonstrated efficacy in the treatment of patients hospitalized with moderate to severe COVID-19. This Phase 3 (GS-US-540–9012) double-blind, placebo-controlled study compared the efficacy and safety of 3 days of RDV to standard of care in non-hospitalized, high-risk participants with confirmed COVID-19. Table 1. COVID-19 related hospitalization or death, COVID-19 related medically attended visits or death, and Treatment Emergent Adverse Events Methods Participants were randomly assigned 1:1 to receive intravenous (IV) RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo. The primary efficacy endpoint was composite COVID-19 hospitalization or all-cause death by day 28 and compared using Cox proportional hazards model with baseline stratification factors as covariates. The primary safety endpoint was proportion of participants with treatment-emergent adverse events. Study enrollment was terminated early for administrative reasons in light of the evolving pandemic. Results 562 patients underwent randomization and started their assigned treatment (279, RDV; 283, placebo). Baseline demographics and characteristics were balanced across arms. Overall, 52% were male, 44% were Hispanic/Latino ethnicity and 30% were ≥ 60 years old. The most common comorbidities were diabetes mellitus (62%), obesity (56%; median BMI, 30.7), and hypertension (48%). Median baseline SARS-CoV-2 RNA nasopharyngeal viral load was 6.2 log10 copies/mL. Treatment with RDV significantly reduced COVID-19 hospitalization or all-cause death by day 28 (HR, 0.13; 95% CI, 0.03 – 0.59; p = 0.008; Table 1) compared to placebo. Participants receiving RDV also had significantly lower risk for COVID-19-related medically attended visits or all-cause death by day 28 compared to placebo (HR, 0.19; 95% CI, 0.07 – 0.56; p = 0.002; Table 1). No deaths occurred in either arm by day 28. There was no difference between arms in time-weighted average change in nasopharyngeal viral loads from baseline up to day 7. The proportion of patients with AEs was similar between arms (Table 1); the most common AEs in the RDV arm were nausea (11%), headache (6%), and diarrhea (4%). Conclusion A 3-day course of IV RDV was safe, well tolerated and highly effective at preventing COVID-19 related hospitalization or death in high-risk non-hospitalized COVID-19 patients. Disclosures Joshua A. Hill, MD, Allogene (Individual(s) Involved: Self): Consultant; Allovir (Individual(s) Involved: Self): Consultant, Grant/Research Support; Amplyx (Individual(s) Involved: Self): Consultant; Covance/CSL (Individual(s) Involved: Self): Consultant; CRISPR (Individual(s) Involved: Self): Consultant; Gilead (Individual(s) Involved: Self): Consultant, Grant/Research Support; Karius: Grant/Research Support, Scientific Research Study Investigator; Medscape (Individual(s) Involved: Self): Consultant; Octapharma (Individual(s) Involved: Self): Consultant; OptumHealth (Individual(s) Involved: Self): Consultant; Takeda (Individual(s) Involved: Self): Consultant, Grant/Research Support, Scientific Research Study Investigator Roger Paredes, MD, PhD, Gilead Sciences, Inc (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Carlos Vaca, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Jorge Mera, MD, Gilead Sciences, Inc (Consultant, Study Investigator (payment to employer not self)) Gilberto Perez, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Godson Oguchi, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Pablo Ryan, MD PhD, Gilead Sciences, Inc (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Jan Gerstoft, MD, Gilead Sciences, Inc (Other Financial or Material Support, Study Investigator (payment to employer)) Michael Brown, FRCP PhD, Gilead Sciences, Inc (Scientific Research Study Investigator, Investigator for numerous remdesivir trials (employer received compensation)) Morgan Katz, MD, MHS, Roche (Individual(s) Involved: Self): Advisor or Review Panel member; Skinclique (Individual(s) Involved: Self): Consultant Gregory Camus, PhD, Gilead Sciences (Employee, Shareholder) Danielle P. Porter, PhD, Gilead Sciences (Employee, Shareholder) Robert H. Hyland, DPhil, Gilead Sciences, Inc (Shareholder, Other Financial or Material Support, Employee during the conduct of this trial) Shuguang Chen, PhD, Gilead Sciences, Inc (Employee, Shareholder) Kavita Juneja, MD, Gilead Sciences, Inc (Employee) Anu Osinusi, MD, Gilead Sciences, Inc (Employee, Shareholder) Frank Duff, MD, Gilead Sciences, Inc (Employee, Shareholder) Robert L. Gottlieb, MD, Eli Lilly (Scientific Research Study Investigator, Advisor or Review Panel member)Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Gift in kind to Baylor Scott and White Research Institute for NCT03383419)GSK (Advisor or Review Panel member)Johnson and Johnson (Scientific Research Study Investigator)Kinevant (Scientific Research Study Investigator)Roche/Genentech (Scientific Research Study Investigator)

LB2. Safety and Efficacy of Combination SARS-CoV-2 Monoclonal Neutralizing Antibodies (mAb) BRII-196 and BRII-198 in Non-Hospitalized COVID-19 Patients

Background SARS-CoV-2 continues to spread and the development of safe and effective therapeutics for the prevention of severe disease remains a priority. BRII-196 and BRII-198 are non-competing anti-SARS-CoV-2 mAbs with YTE triple amino acid substitution in Fc to extend half-life and reduce receptor binding, that are being studied for treatment of COVID-19 in the ACTIV-2 Trial, sponsored by NIAID and led by ACTG. Methods ACTIV-2 evaluates safety/efficacy of investigational agents for treatment of non-hospitalized adults with mild-moderate COVID-19 under a randomized, blinded, controlled adaptive platform. BRII-196/BRII-198 (1000 mg each) as a single dose given as sequential infusions, or placebo to those at high risk of clinical progression (i.e., age ≥ 60 years or presence of other medical conditions) within 10 days of symptom onset and positive test for SARS-CoV-2. The primary endpoint was hospitalization and/or death through day 28. We report Phase 3 BRII-196/BRII-198 trial results per DSMB recommendation following an interim analysis. Results Between January and July 2021, 837 participants (418 active, 419 placebo) from sites in the US (66%), Brazil, South Africa, Mexico, Argentina and the Philippines were randomized and received study product at time of emerging variants. Median age 49 years (Q1, Q3: 39, 58), 51% female, 17% Black/African-American and 49% Hispanic/Latino, with median 6 days from symptom onset. At interim analysis 71% and 97% had a day 28 and 7 visit, respectively. For all available data at interim review, BRII-196/BRII-198 compared to placebo had fewer hospitalizations (12 vs. 45) and deaths (1 vs. 9). At day 28 of follow-up, there was an estimated 78% reduction in hospitalization and/or death (2.4 vs. 11.1%), relative risk 0.22 (95% CI: 0.05, 0.86), P=0.00001 (nominal one-sided). Grade 3 or higher adverse events (AEs) were observed less frequently among BRII-196/BRII-198 participants than placebo (3.8% vs. 13.4%) with no severe infusion reactions or drug related serious AEs. Conclusion BRII-196/BRII-198 was safe, well-tolerated, and demonstrated significant reduction compared to placebo in the risk of hospitalization and/or death among adults with mild-moderate COVID-19 at high risk for progression to severe disease. Disclosures Kara W. Chew, MD, MS, Amgen (Individual(s) Involved: Self): Grant/Research Support; Merck Sharp & Dohme (Individual(s) Involved: Self): Grant/Research Support David Alain Wohl, MD, Gilead Sciences (Individual(s) Involved: Self): Advisor or Review Panel member, Consultant, Research Grant or Support, Scientific Research Study Investigator; Janssen (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support; ViiV (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV (Consultant, Research Grant or Support) David A. Margolis, MD MPH, Brii Biosciences (Employee) Courtney Fletcher, Pharm.D., National Institute of Allergy and Infectious Diseases, NIH (Grant/Research Support) Davey Smith, M.D., Linear Therapies, Matrix Biomed, Bayer (Consultant, Shareholder) Eric Daar, Gilead (Consultant, Grant/Research Support)Merck (Consultant)ViiV (Consultant, Grant/Research Support)

1334. Outcomes Among Influenza and SARS-CoV-2 Infection in Hospitalized Adults Age ≥ 50 Years and with Underlying Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF)

Background A significant burden of disease exists for adults infected with influenza (flu) and SARS-CoV-2, which causes COVID-19. However, data are limited comparing outcomes between hospitalized adults infected with these viruses. Methods Over the course of 3 consecutive winter respiratory viral seasons, adults ≥ 50 years of age admitted with acute respiratory tract infections (ARI) and adults of any age with COPD or CHF-related admissions were enrolled from 2 Atlanta area hospitals. For the 2018-19 and 2019-20 seasons, participants were approached in the hospital. If the participant enrolled, nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected and tested using BioFire® FilmArray® respiratory panel. Due to the COVID-19 pandemic in 2020-21 and limitations involving participant contact, only NP standard of care (SOC) swabs were collected. A comprehensive medical chart review was completed for each subject which encompassed data on their hospitalization, past medical history, and vaccination history. Co-infected patients were excluded from the analyses. Results Of the eligible participants, 118 were flu positive (three RSV-influenza co-infections were excluded) and 527 were COVID-19 positive. Median age was lower for the flu cohort at 62 (IQR 56-71) than those with COVID-19 (67, IQR 59-77) (p < 0.0001). Length of stay (LOS) was shorter in flu-infected patients (median 3 d, IQR 2-6), but was longer for COVID-19 patients (median 5 d, IQR 3-10). ICU admission occurred in 20% of those with flu, and among those admitted to the ICU mechanical ventilation (MV) occurred in 12.5%. ICU admission and MV was significantly higher for those with COVID-19, with 28% of patients admitted to the ICU and 47% of those requiring MV. Among patients with COVID-19, 8.9% died. This was significantly higher than that of flu (3.4%) (p=0.008). Hospital discharge occurred more frequently to a nursing home or LTCF with COVID-19 (10.3%) than with flu (0%) (p< 0.0001). Table 1. Breakdown of age, hospitalization course, and discharge disposition for participants diagnosed with influenza or COVID-19 during hospitalization. Conclusion COVID-19 resulted in a longer hospital admission, a greater chance of ICU admission and MV as compared to flu. Additionally, COVID-19 participants had a high rate of discharge to a nursing home/LTCF and a significantly higher risk of death. While the clinical course was not as severe as COVID-19, influenza contributed a significant burden. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory; Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

1189. COVID 19 Infection in Children in Colombia, Experience from a Nationwide Network (CORONARED)

Background Worldwide SARS-CoV-2 infections increase every day. Despite the infection is less severe in children, it can be severe and associated with complications. However, local data remain scarce. We sought to describe epidemiological and clinical characteristics of COVID-19 infection in this population across different age groups. Methods Observational, multicenter study across 23 Colombian hospitals from 22 different territories. We included all patients from 0 months to 17 years with confirmed SARS-CoV-2 infection by either antigen or RT-PCR testing. Results From March 1, 2020, to October 31, 2021, we identified 1,186 patients: neonates (88), 1 to 3 months (130), 4 to 23 months (306), 2 to 4 years (169), 5 to 11 years (229) and 12 to 18 years (226) with confirmed COVID-19 infection. Of those,77(6.2%) were asymptomatic, 631(53.2%) hospitalized, 132(11.2%) required PICU. 58 cases met WHO definition of MIS-C. Patients less than 24 months of age were characterized by fever (74%) and more respiratory distress (30.1%) compared to other groups. Patients >5yo seemed to have a more severe presentation. They had more gastrointestinal (GI) symptoms (31% vs 37.8%), had more need for ICU care given presentation with shock increased with age ( >5yo 9.5%; 5-12yo 10.6%; 12-18yo 11.5%). Lab markers including thrombocytopenia and Lymphopenia were more common on this age group. Antibiotic treatment was common (%%) especially in neonates (40.9%), despite bacterial coinfection was rare (8.7%), length of hospitalization was longer in older than 2-year-old groups. 23(1.9%) patients died, similar across different age groups. Heat map by age group Conclusion COVID-19 infection in Colombian children presented differently across different age groups. Children older than 5 years had a more severe clinical course and prolonged hospital stays. Clinical findings according to age groups could help clinicians in characterizing and identifying COVID 19 infections in Children. Disclosures Ivan Felipe Gutiérrez Tobar, n/a, Pfizer and MSD (Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau, Has received support from Pfizer and MSD for participation in congresses and has received conference payments from Pfizer)Pfizer and MSD (Speaker’s Bureau, Other Financial or Material Support, Has received support from Pfizer for participation in congresses) Juan P. Rojas -Hernandez, Candidate for doctorate in Public Health, Pfizer (Other Financial or Material Support, Has received support from Pfizer for participation in congresses) Eduardo López Medina, n/a, Pfizer (Other Financial or Material Support, Has received support from Pfizer for participation in congresses)

01. Serum Bactericidal Activity Against Circulating and Reference Strains of Meningococcal Serogroup B in the United States: A Review of Meningococcal Serogroup B (MenB) Vaccines in Adolescents and Young Adults

Background US adolescents and young adults are at particular risk of invasive meningococcal disease (IMD). In 2018, menincococcal serogroup B was responsible for 36% of IMD cases in the US overall and for 66% of cases in adolescents and young adults. This age group is at high risk of IMD during outbreaks, which result in significant response-related costs. MenB vaccine efficacy against IMD relies on its ability to provide broad protection against diverse disease-causing strains. MenB-FHbp (Trumenba) and MenB-4C (Bexsero) are MenB vaccines licensed in the US as 2-dose series with an interval of 6 mo or 1 mo, respectively, recommended in healthy adolescents and young adults. We review available data on vaccine coverage of serogroup B strains. Methods A literature review identified relevant information from peer-reviewed publications, congress presentations, and ClinicalTrials.gov. Previously presented but unpublished data from phase 2/3 studies were included. Results After 2 MenB-FHbp doses, percentages of adolescents and young adults achieving serum bactericidal activity assay using human complement (hSBA) titers ≥1:8 were 79%–99% for 4 heterologous representative test strains and 71%–97% for 10 additional strains, confirming cross-protection against a diverse strain panel (Figure 1; unpublished data). These 14 heterologous strains collectively represent ~80% of disease-causing strains in the US and Europe. In a published study with limited sample size, 44%–78% of subjects had hSBA titers ≥1:8 against strains from 4 US college outbreaks after 2 MenB-FHbp doses. After 2 MenB-4C doses, percentages of 10–25-year-olds achieving hSBA titers ≥1:5 against 3 reference strains homologous to the vaccine antigen were 82%–93% (published data); 15%–100% of adolescents achieved hSBA titers ≥1:4 against a panel of 14 strains (unpublished data). Of college students who received 2 MenB-4C doses, 53%–93% achieved hSBA titers ≥1:4 against 5 US outbreak strains (4/5 strains had antigenic similarity to MenB-4C; published data). Conclusion MenB-FHbp and MenB-4C protect against various serogroup B strains. As for the breadth of coverage provided by these vaccines, available data show that MenB-FHbp elicits robust immune responses to a wide variety of disease-causing strains prevalent in the US (Figure 2). Disclosures Tamera Coyne-Beasley, MD, MPH, Pfizer Inc and GlaxoSmithKline (Advisor or Review Panel member) Joseph Bocchini, MD, Pfizer Inc and Dynavax (Advisor or Review Panel member) Alejandro Cane, M.D., Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Maria J. Tort, PhD, Pfizer Inc (Employee, Shareholder) Jessica Presa, MD, Pfizer Inc (Employee, Shareholder)

1161. Increasing incidence of Sinogenic Intracranial Infections in Utah Children 2004-2019

Background Intracranial extension of sinusitis is a rare complication. Non-specific presentations are a diagnostic challenge, and complications include long-term neurologic sequelae. Early recognition is critical, although optimal management remains poorly characterized. Methods We conducted a retrospective chart review of 123 patients admitted to Primary Children’s Hospital between 2004-2019 with ICD9 and ICD10 codes for sinusitis and intracranial suppurative infection. Chart review confirmed cases in patients < 18 years with evidence of sinusitis and intracranial extension. Variables collected included: demographic data, clinical presentation, microbial profile, clinical management, and outcomes. Results We observed 84 pediatric sinogenic intracranial infections between 2004-2019. Incidence significantly increased over the interval. Median patient age was 12.8 years (IQR 10.5-14.7 years); most were male (n=52). The most common presenting symptoms were headache and fever. Most patients (n=80) required surgical management; 62 required neurosurgery. All but one patient survived. Most infections were polymicrobial (n=47). Streptococcus anginous group were most frequently identified (n=32). All patients were started on vancomycin empirically; only 10 required use for definitive management. Most patients were treated with a carbapenem (n=42) or ceftriaxone plus metronidazole (n=32). Average duration of antibiotics was 44 days (IQR 38-55 days). The most common complication was epilepsy (n=11). Patients with Streptococcus sp. infections were more likely to experience adverse outcomes (p= 0.04). We observed significantly decreased carbapenem use following introduction of an antimicrobial stewardship program in 2012, with no change in clinical outcomes. Annual incidence of Sinogenic Intracranial Infections Shown is the increasing incidence of sinogenic intracranial infections annually in the state of Utah/100,000 children. Conclusion Sinogenic intracranial infections are increasingly frequent severe pediatric infections with associated long term neurologic sequelae. Most patients require both surgical and long-term IV antibiotic treatment. Most infections are polymicrobial. Streptococcus sp. are commonly identified. Antibiotic resistant bacteria are rare. The combination ceftriaxone and metronidazole is appropriate for treatment of most infections. Disclosures Anne Bonkowsky, MD/PhD, BioFire Diagnostics (Consultant, Grant/Research Support, Other Financial or Material Support, I have intellectual property through the University of Utah in BioFire Diagnostics and the FilmArray and receive royalties through the University of Utah.)Merck (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

Background RSV 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. Methods Primary 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. Results AUC 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. Conclusion Higher 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)

1178. Sustained Vaccine Effectiveness Against Influenza-Associated Hospitalization in Children: Evidence from the New Vaccine Surveillance Network, 2015-2016 Through 2019-2020

Background Adult studies have demonstrated intra-season declines in influenza vaccine effectiveness (VE) with increasing time since vaccination; however, data in children are limited. Methods We conducted a prospective, test-negative study of children ages 6 months through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers each season in the New Vaccine Surveillance Network during the 2015-2016 through 2019-2020 influenza seasons. Cases were children with an influenza-positive molecular test; controls were influenza-negative children. Controls were matched to cases by illness onset date using 3:1 nearest neighbor matching. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥ 1 dose of influenza vaccine ≥ 14 days before the onset of illness that resulted in hospitalization among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date during each season were estimated using multivariable logistic regression models. Results Of 8,430 hospitalized children (4,781 [57%] male; median age 2.4 years), 4,653 (55%) received ≥ 1 dose of influenza vaccine. On average, 48% and 85% of children were vaccinated by the end of October and December, respectively. Influenza-positive cases (n=1,000; 12%) were less likely to be vaccinated than influenza-negative controls (39% vs. 61%, p< 0.001) and overall VE against hospitalization was 53% (95% CI: 46%, 60%). Pooling data across 5 seasons, the odds of any influenza-associated hospitalization increased 0.96% (95% CI: -0.76%, 2.71%) per week with a corresponding weekly decrease in VE of 0.45% (p=0.275). Odds of hospitalization with time since vaccination increased 0.66% (95% CI: -0.76%, 2.71%) per week in children ≤ 8 years (n=3,084) and 2.16% (95% CI: -1.68%, 6.15%) per week in children 9-17 years (n=771). No significant differences were observed by virus subtype or lineage. Figure 1. Declines in influenza VE over time from 2015-2016 through 2019-2020, overall (a) and by age group (b: ≤ 8 years; c: 9-17 years) Conclusion We observed minimal intra-season declines in VE against influenza-associated hospitalization in U.S. children. Vaccination following Advisory Committee on Immunization Practices guidelines and current timing of vaccine receipt is the best strategy for prevention of influenza-associated hospitalization in children. Disclosures Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)