32. Host Immune-Protein Signature Combining TRAIL, IP-10 and CRP for Early and Accurate Prediction of Severe COVID-19 Outcome

Abstract Background Accurately identifying COVID-19 patients at-risk to deteriorate remains challenging. Dysregulated immune responses impact disease progression and development of life-threatening complications. Tools integrating host immune-protein expression have proven useful in determining infection etiology and hold potential for prognosticating disease severity. Methods Adults with COVID-19 were enrolled at medical centers in Israel, Germany, and the United States (Figure 1). Severe outcome was defined as intensive care unit admission, non-invasive or invasive ventilation, or death. Tumor necrosis factor related apoptosis inducing ligand (TRAIL), interferon gamma inducible protein-10 (IP-10) and C-reactive protein (CRP) were measured using an analyzer providing values within 15 minutes (MeMed Key®). A signature indicating the likelihood of severe outcome was derived generating a score (0-100). Description of derivation cohort RT-PCR, reverse transcription polymerase chain reaction. Results Between March and November 2020, 518 COVID-19 patients were enrolled, of whom 394 were eligible, 29% meeting a severe outcome. Age ranged between 19-98 (median 61.5), with 59.1% male. Patients meeting severe outcomes exhibited higher levels of CRP and IP-10 and lower levels of TRAIL (Figure 2; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The signature’s area under the receiver operating characteristic curve (AUC) was 0.86 (95% confidence interval: 0.81-0.91). Performance was not confounded by age, sex, or comorbidities and was superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Clinical deterioration proximal to blood draw was associated with higher signature score. Scores of patients meeting a first outcome over 3 days after blood draw were significantly (p < 0.001) higher than scores of non-severe patients (Figure 3). Moreover, the signature differentiated patients who further deteriorated after meeting a severe outcome from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001; Figure 4). TRAIL, IP-10, CRP and the severity signature score are differentially expressed in severe and non-severe COVID-19 infection Dots represent patients and boxes denote median and interquartile range (IQR) The signature score of patients meeting a severe outcome on or after the day of blood draw is significantly (p < 0.001) higher than the signature score of non-severe patients. Dots represents patients and boxes denote median and IQR Kaplan-Meier survival estimates for signature score bins Conclusion The derived signature combined with a rapid measurement platform has potential to serve as an accurate predictive tool for early detection of COVID-19 patients at risk for severe outcome, facilitating timely care escalation and de-escalation and appropriate resource allocation. Disclosures Alon Angel, n/a, MeMed (Employee, Shareholder) Niv Samuel Mastboim, BSc, MeMed (Employee, Shareholder) Oded Shaham, PhD, MeMed (Employee, Shareholder) Tahel Ilan Ber, MD, MeMed (Employee, Shareholder) Roy Navon, MSc, MeMed (Employee, Shareholder) Einav Simon, PhD, MeMed (Employee, Shareholder) Michal Rosenberg, PhD, MeMed (Employee) Yael Israeli, PhD, MeMed (Employee) Mary Hainrichson, PhD, MeMed (Employee, Shareholder) Noa Avni, PhD, MeMed (Employee) Eran Reiner, MD, MeMed (Employee) Kfir Oved, MD, PhD, MeMed (Board Member, Employee, Shareholder) Ilya Kagan, MD, MeMed (Scientific Research Study Investigator) Shaul Lev, M.D, MeMed (Scientific Research Study Investigator) Dror Diker, MD, MeMed (Scientific Research Study Investigator) Amir Jarjou’i, MD, MeMed (Scientific Research Study Investigator) Ramzi Kurd, MD, MeMed (Scientific Research Study Investigator) Guy Danziger, MD, MeMed (Scientific Research Study Investigator) Cihan Papan, MD, MeMed (Scientific Research Study Investigator) Sergey Motov, MD, MeMed (Scientific Research Study Investigator) Maanit Shapira, Ph.D, MeMed (Scientific Research Study Investigator) Tanya Gottlieb, PhD, MeMed (Employee, Shareholder) Eran Eden, PhD, MeMed (Board Member, Employee, Shareholder)

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1393. Factors Associated with Co-administration of Pentavalent DTaP-IPV/Hib and Monovalent Hepatitis B Vaccine in the United States (US)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1575 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S706-S706

Author(s):

Tanaz Petigara ◽

Ya-Ting Chen ◽

Zhiwen Liu ◽

Michelle Goveia ◽

David Johnson ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

The United States ◽

Vaccination Schedule ◽

Provider Type ◽

Factors Associated ◽

Study Investigator ◽

Region Of Residence ◽

Birth Dose ◽

To Receive

Abstract Background The US vaccination schedule includes DTaP, IPV, Hib and HepB doses in the first 6 months of life. A previous analysis found variability in the timing of HepB doses in infants receiving DTaP-IPV/Hib. We explored factors associated with co-administration of DTaP-IPV/Hib and HepB on the same day. Methods This was a retrospective study using the MarketScan® commercial claims and encounters database. Infants born from 1 July 2010 - 30 June 2016, continuously enrolled in an insurance plan for ≥ 13 months and receiving ≥ 3 DTaP-IPV/Hib doses were included. Infants were assessed for HepB claims relative to the first and third DTaP-IPV/Hib doses. Because a HepB birth dose was assumed, the first HepB claim from 29 - 169 days following birth was counted as Dose 2, and the second claim from 170 days - 12 months as Dose 3. Associations between demographic, provider, and insurance characteristics, receipt of other pediatric vaccines, and co-administration of DTaP-IPV/Hib and HepB were analyzed using multivariate logistic regression. Results Among 165,553 infants who received a first DTaP-IPV/Hib dose, 60.7% received HepB Dose 2 on the same day. Among 162,217 infants who received a third DTaP-IPV/Hib dose, 45.1% received HepB Dose 3 on the same day. Infants in the Northeast were less likely (OR=0.38, 95%CI=0.36-0.39), while those in the West were more likely (OR=1.41, 95%CI=1.36-1.46) than infants in the South to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day. Infants vaccinated by pediatricians (OR=0.54, 95%CI=0.53-0.55) were less likely to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day compared to infants vaccinated by family physicians. Infants who received PCV on the same day as the first dose of DTaP-IPV/Hib were more likely to receive HepB Dose 2 (OR=6.96, 95%CI=6.30-7.70) that day. These factors were also associated with co-administration of the third dose of DTaP-IPV/Hib and HepB Dose 3. Conclusion Differences in co-administration of DTaP-IPV/Hib and HepB were associated with region of residence, provider type and co-administration of PCV. The reasons underlying these differences merit exploration. A hexavalent vaccine containing DTaP, IPV, Hib, and HepB could improve timeliness of HepB vaccination, while reducing the number of injections during infancy. Disclosures Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Zhiwen Liu, PhD, Merck & Co., Inc., (Employee) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

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1386. Current Estimates of the Impact of Routine Childhood Immunizations in Reducing Vaccine-Preventable Diseases in the United States

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1568 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S703-S703

Author(s):

Elizabeth M La ◽

Justin Carrico ◽

Sandra E Talbird ◽

Ya-Ting Chen ◽

Mawuli K Nyaku ◽

...

Keyword(s):

United States ◽

Research Study ◽

Disease Incidence ◽

Age Groups ◽

Scientific Research ◽

The United States ◽

Annual Number ◽

Study Investigator ◽

Routine Childhood ◽

The Impact

Abstract Background Routine immunizations for children aged 10 years and younger in the United States (US) currently cover 14 diseases. Updated estimates of public health impact are needed, given changes in disease epidemiology, evolving recommendations, and the dynamic nature of compliance with the immunization schedule. Methods Pre-vaccine disease incidence was estimated before each routine vaccine was recommended, with average values across multiple years obtained directly from published literature or calculated based on disease surveillance data or annual case estimates from the published literature. Pre-vaccine incidence then was compared to current, post-vaccine incidence, which was generally calculated as average values over the most recent 5 years of available incidence data. Overall incidence estimates and estimates by age group were calculated. Differences in pre- and post-vaccine disease incidence rates were used to calculate the annual number of cases averted, based on 2019 US population estimates. This analysis did not separately estimate the proportion of disease incidence reduction that may be attributed to adult vaccines or booster doses. Results Post-vaccine disease incidence decreased overall and for all age groups across all diseases evaluated (Table 1). Decreases ranged from 17.4% for influenza to 100.0% for polio (Figure 1). Over 90% reduction in incidence was achieved for 10 of the 14 diseases evaluated (including reduction in incidence of rotavirus hospitalizations). Overall post-vaccine disease incidence estimates were highest for influenza, rotavirus, and varicella. Estimated annual cases averted by vaccination in 2019 ranged from 1,269 for tetanus to more than 4.2 million for varicella. Table 1. Pre- and Post-Vaccine Disease Incidence Estimates, Annual Cases, and 2019 Cases Averted, by Disease Figure 1. Percentage Reduction in Disease Incidence Post-Vaccine, by Disease Conclusion Routine childhood immunization in the US continues to result in high, sustained reduction in disease across all vaccines and for all age groups evaluated. Disclosures Elizabeth M. La, PhD, RTI Health Solutions (Employee) Justin Carrico, BS, GlaxoSmithKline (Consultant) Sandra E. Talbird, MSPH, RTI Health Solutions (Employee) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Mawuli K. Nyaku, DrPh, Merck & Co. Inc. (Employee, Shareholder) Cristina Carias, PhD, Merck (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator) Craig S. Roberts, PharmD, MPA, MBA, Merck & Co., Inc (Employee, Shareholder)

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1399. Parental Perceptions of the Childhood Vaccination Schedule and Combination Vaccines in the United States (US)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1581 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S708-S708

Author(s):

Tanaz Petigara ◽

Xinyi Ng ◽

Ya-Ting Chen ◽

Jyoti Aggarwal ◽

Jenna Bhaloo ◽

...

Keyword(s):

Online Survey ◽

Research Study ◽

Scientific Research ◽

The United States ◽

Vaccination Schedule ◽

Childhood Vaccination ◽

Multiple Injections ◽

Study Investigator ◽

Vaccine Schedule ◽

Combination Vaccines

Abstract Background Ten different vaccine series are recommended by the US Advisory Committee on Immunization Practices from birth to 18 months. Combination vaccines can reduce the number of injections and visits required to complete the schedule in a timely manner. There is limited current information on parents’ perception of the vaccine schedule and combination vaccines. Methods An online survey was completed by 100 parents who had at least one child under 2 years, were involved in vaccination decisions, and had accompanied their child to a vaccination appointment. Parents who reported not ever vaccinating their children were excluded. Parents’ perception of, and adherence to, the recommended schedule, communication with providers, and knowledge of combination vaccines were collected. Descriptive analyses were performed. Results Ninety-six percent of parents (mean age=30.7 years; range 19.0-50.0; 91% white) reported their provider as a source of vaccination information, followed by internet searches (63%), family and friends (45%). Most (84%) followed all their provider’s recommendations and trusted the information given to them (87%). State day care and pre-school requirements influenced vaccination decisions for nearly 80% of parents. Over 80% of parents thought it is important to protect against diseases covered by the vaccination schedule. One-third had at some time asked to delay or not administer vaccines; depending on the vaccine, up to 50% ultimately had their child vaccinated as recommended. Top reasons for delaying vaccination were to avoid crying and pain from multiple injections (82%), and the concern that too many vaccines would overwhelm the immune system (64%). Top reasons for refusal were religious views (57%) and the belief that the vaccine was not needed (52%). On average, parents would accept their child receiving 3 injections in one visit. Most parents were aware of combination vaccines (84%); however, one-third reported that their child had not received, or they were unaware of their child receiving, a combination vaccine. Conclusion Providers are in a strong position to influence vaccination decisions by parents. Whereas parents are motivated to avoid the pain of multiple injections, many are unaware that their children are receiving combination vaccines. Disclosures Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Xinyi Ng, PhD, Merck & Co., Inc. (Consultant) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Jyoti Aggarwal, MHS, Merck & Co., Inc. (Consultant) Jenna Bhaloo, MPH, Merck & Co., Inc. (Consultant) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

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1514. Mortality and Readmission in Adults during the First Year Following Hospitalization for Community-Acquired Pneumonia in the US

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1695 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S760-S760

Author(s):

Reiko Sato ◽

Derek Weycker ◽

Melody Shaff ◽

Ahuva Hanau ◽

Alexander Lonshteyn ◽

...

Keyword(s):

At Risk ◽

High Risk ◽

Hospital Readmission ◽

Research Study ◽

Scientific Research ◽

Research Support ◽

Post Discharge ◽

Study Investigator ◽

Comorbidity Profile ◽

Research Grant

Abstract Background Increasing evidence suggests that the impact of community-acquired pneumonia (CAP) extends beyond discharge from the hospital and the acute phase of illness. We sought to characterize mortality and hospital readmission across the adult age span and spectrum of comorbidities. Methods A retrospective cohort design and data from Optum’s de-identified Integrated Claims-Clinical dataset (2009-2018) were employed. Study population comprised all adults who, between 1.1.2013 and 12.31.2017, had ≥ 1 acute-care hospitalization for CAP; each qualifying CAP hospitalization separated by ≥ 365 days was included as a unique observation in analyses. Study outcomes included acute-care hospital readmission for any reason and death for any reason. Hospital readmission was ascertained during the 360-day period following discharge from the CAP hospitalization; death was ascertained during the CAP hospitalization as well as during the same 360-day period. Cumulative rates of mortality and readmission were summarized for all patients as well as subgroups defined on age and comorbidity profile (i.e., healthy, at-risk, high-risk). Results Study population totaled 37,006 patients who contributed 38,809 CAP hospitalizations; mean age was 71 years, 51% were female, and 88% had an at-risk (33%) or high-risk (55%) condition. Hospital readmission was 12.5% during the 30-day post-discharge period, and 42.3% during the 360-day post-discharge period. Mortality was 3.5% in hospital, 8.2% from admission to 30 days post-discharge, and 17.7% from admission to 360 days post-discharge. Mortality rates increased with age and severity of comorbidity profile; readmission rates were highest for persons aged 65-74 years and high-risk persons. Rates of readmission and mortality among adults hospitalized for CAP Conclusion All-cause mortality up to 1 year following hospital admission for CAP was substantial, and was associated with increasing age and worsening comorbidity profile. Both readmission and mortality were greater at all ages in high-risk and at-risk groups compared with their healthy counterparts. Strategies that prevent pneumonia and/or the pathophysiologic changes that follow CAP, especially among individuals with comorbid conditions, have the potential to reduce morbidity and mortality following CAP as well as healthcare costs associated with readmission. Disclosures Reiko Sato, PhD, Pfizer, Inc (Employee, Shareholder) Derek Weycker, PhD, Pfizer Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Melody Shaff, BA, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Ahuva Hanau, BS, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Alexander Lonshteyn, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant)

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19. The Impact of Investigational Purified Microbiome Therapeutic SER-109 on Health-Related Quality of Life (HRQoL) of Patients with Recurrent Clostridioides difficile Infection (rCDI) in ECOSPOR III, a Placebo-Controlled Clinical Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.019 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S13-S13

Author(s):

Elizabeth Hohmann ◽

Paul Feuerstadt ◽

Caterina Oneto ◽

Charles Berenson ◽

Christine Lee ◽

...

Keyword(s):

Treatment Group ◽

Clinical Outcome ◽

Board Member ◽

Research Study ◽

Scientific Research ◽

Research Support ◽

Independent Contractor ◽

Study Investigator ◽

The Impact ◽

Research Grant

Abstract Background Following standard of care antibiotics, investigational microbiome therapeutic, SER-109, achieved superiority vs placebo (PBO) at 8 weeks in reducing rCDI in patients with ≥3 prior episodes (12.4% vs 39.8%, respectively; p< 0.001). We evaluated the impact of SER-109 vs PBO on HRQoL with general (EQ-5D-5L) and disease-specific (Cdiff32) measures [Garey 2016]. Methods EQ-5D-5L measures outcomes in 5 domains (mobility, self-care, activities, pain/discomfort, and anxiety/depression) while Cdiff32 measures outcomes in 3 domains (physical, mental, and social) including 5 associated subdomains. Patients completed EQ-5D-5L and Cdiff32 measures at baseline (BL), Wk 8, and at recurrence/early termination. Changes from BL were assessed between SER-109 vs PBO and by clinical outcome (recurrence versus nonrecurrence) in the ITT population and within each treatment arm. The between treatment group comparison analysis controlled for age, gender, prior antibiotics, and number of prior CDI episodes. Results Mean EQ-5D-5L and Cdiff32 scores were comparable between SER-109 and PBO at BL. EQ-5D-5L did not detect differences at Wk 8 from BL between SER-109 and PBO or by clinical outcome. In contrast, Cdiff32 detected significant improvements at Wk 8 from BL within both SER-109 subjects and PBO subjects (Fig1) and by recurrence status (Fig2). Subjects achieved significant improvement in all domains at Wk 8 from BL regardless of treatment group. When examining recurrence status within treatment arms, all PBO subjects with non-recurrence showed improvement in all health domains, while PBO subjects with recurrence had declines in several subdomains (Fig3B). Similarly, SER-109 subjects with non-recurrence showed improvement in all domains compared to BL. However, overall and mental domain/subdomains scores also improved in SER-109 subjects with recurrence (Fig3A). Conclusion Significant HRQoL improvements were associated with CDI nonrecurrence, which highlights the negative impact of this debilitating infection. SER-109 was associated with improved overall and mental scores, regardless of clinical outcome. Further investigation is warranted on the impact of SER-109 on mental health even among those with CDI recurrence. Disclosures Elizabeth Hohmann, MD, Seres Therapeutics (Research Grant or Support) Paul Feuerstadt, MD, FACG, Ferring/Rebiotix Pharmaceuticals (Consultant, Scientific Research Study Investigator, Speaker’s Bureau)Finch Pharmaceuticals (Scientific Research Study Investigator)Merck and Co (Speaker’s Bureau)SERES Therapeutics (Consultant, Scientific Research Study Investigator)Takeda Pharmaceuticals (Consultant) Christine Lee, MD, FRCPC, Pfizer (Board Member)Rebiotix-Ferring (Board Member)Rebiotix-Ferring (Grant/Research Support)Seres (Grant/Research Support)Summit (Grant/Research Support) Sissi Pham, PharmD, Seres (Consultant) Pat Ray Reese, PhD, Reese Associates, LLC (Consultant, Independent Contractor) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder) Kevin W. Garey, Pharm.D., M.S., FASHP, Summit Therapeutics (Research Grant or Support)

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1394. Impact of 7-Valent and 13-Valent Pneumococcal Conjugate Vaccines in the United States: A Systematic Literature Review

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1576 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S706-S706

Author(s):

Kristin Kistler ◽

Evelyn F Gomez-Espinosa ◽

Kelly Sutton ◽

Ruth Chapman ◽

Desmond Dillon-Murphy ◽

...

Keyword(s):

United States ◽

Literature Review ◽

Systematic Literature Review ◽

Pneumococcal Disease ◽

Research Study ◽

Scientific Research ◽

The United States ◽

Conjugate Vaccines ◽

Pneumococcal Conjugate Vaccines ◽

Study Investigator

Abstract Background The availability of 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines (PCVs) in the United States (US) since 2000 and 2010, respectively, has substantially reduced the occurrence, morbidity and mortality of pneumococcal disease. This systematic literature review aimed to assess the impact of the PCVs in reducing the pneumococcal disease burden since their introduction. Methods We searched Embase and Medline and disease-surveillance websites for observational studies of US participants < 19 years, published 1999–2019 and reporting incidence or prevalence of acute otitis media, invasive pneumococcal disease, meningitis, or pneumococcal disease-related morbidity, mortality, healthcare resource utilization (HCRU) or costs. Results Of 499 citations identified from the databases and other sources, 125 met inclusion criteria (Figure), all indicating clear reductions in multiple manifestations of pneumococcal disease with PCV7 and PCV13 use. However, variations across studies in outcomes reported, study years, and age strata, confounded assessment of vaccine impact on specific pneumococcal disease outcomes and key burden indicators, such as tympanostomy tube placement and antibiotic prescriptions. Conclusion PCVs have greatly decreased multiple manifestations of pneumococcal disease in the US. However, granular data on the frequency and morbidity associated with specific pneumococcal diseases and on associated HCRU are needed to quantify the public-health impact of these vaccines. Disclosures Kristin Kistler, PhD, Evidera, Inc. (Employee, Evidera, Inc. received the funding to conduct this study.) Evelyn F. Gomez-Espinosa, BSc, PhD, Evidera Inc (Employee, Scientific Research Study Investigator)Pfizer Inc (Consultant, Scientific Research Study Investigator) Kelly Sutton, PhD, Evidera (Other Financial or Material Support, Evidera, Inc. received the funding to conduct this study.) Ruth Chapman, MSc, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Desmond Dillon-Murphy, MSc, PhD, Evidera, Inc. (Evidera, Inc. received the funding to conduct this study.) (Consultant) Matthew Wasserman, MSc., Pfizer Inc. (Employee)

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584. Phase 1 Placebo-Controlled Trial of COVI-VAC™, an Intranasal, Live Attenuated COVID-19 Vaccine

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.782 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S394-S394

Author(s):

Sybil Tasker ◽

Daryl Bendel ◽

Melissa Bevan ◽

Steffen Mueller ◽

Anna Kushnir ◽

...

Keyword(s):

Young Adults ◽

Adverse Events ◽

Board Member ◽

Research Study ◽

Serum Antibody ◽

Scientific Research ◽

Viral Shedding ◽

Study Investigator ◽

Furin Cleavage Site ◽

Viral Vaccine

Abstract Background COVI-VACTM is an intra-nasal live-attenuated SARS-COV-2 synthetic viral vaccine being developed for the prevention of COVID-19. COVI-VAC is attenuated through deletion of the furin cleavage site and introduction of 283 silent deoptimizing mutations that maintain viral amino acid sequence but result in significant attenuation due to slow translation in the human host cell. Notably, COVI-VAC includes all viral antigens and is not limited to spike. COVI-VAC has demonstrated attenuation, immunogenicity and single dose protection in both Syrian golden hamster and non-human primate models. Methods 48 healthy young adults were enrolled in an inpatient quarantine setting to one of 3 dose escalating cohorts and randomized to COVI-VAC or saline placebo given as nose drops, as a single 0.5mL dose or 2 doses 28 days apart. Endpoints included solicited and unsolicited adverse events, serum cytokines, viral shedding and sequence stability, mucosal and serum antibody responses and IFN ELISpot. Subjects will be followed for 1 year for late safety events and durability of immune response. Results Dosing is complete. There has been no trend in solicited reactogenicity events, and all unsolicited adverse events reported to date have been mild. There have been no SAEs or Grade 3 or 4 events. Vaccine virus from anonymized subjects was shed at levels lower than that likely to result in onward transmission, and the deoptimized sequence of the shed virus remained unchanged compared to the original vaccine sequence. Unblinded data including immunogenicity will be available prior to the IDWeek meeting. Conclusion COVI-VAC appears safe and well tolerated in healthy young adults. Vaccination resulted in minimal viral shedding without sequence instability. Safety and shedding data supports continued development in a wider Phase 2/3 population. Disclosures Sybil Tasker, MD, MPH, FIDSA, Codagenix Inc (Employee, Shareholder) Daryl Bendel, MD, Codagenix Inc (Scientific Research Study Investigator) Melissa Bevan, MD, Codagenix Inc (Scientific Research Study Investigator) Steffen Mueller, PhD, Codagenix Inc (Board Member, Employee, Shareholder) Anna Kushnir, PHD, Codagenix Inc (Employee) Brandon Londt, PhD, Codagenix Inc (Other Financial or Material Support, contracted lab services) J. Robert Coleman, PhD, Codagenix Inc. (Board Member, Employee, Shareholder)

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1150. Pediatric Osteoarticular Infections Caused by Mycobacteria Tuberculosis Complex: A Twenty-Six Year Review of Cases in San Diego, California

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1343 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S666-S667

Author(s):

Ian Drobish ◽

Nanda Ramchandar ◽

Vanessa Raabe ◽

Alice Pong ◽

John S Bradley ◽

...

Keyword(s):

Research Study ◽

Bone Biopsy ◽

Scientific Research ◽

The United States ◽

Sample Type ◽

Tuberculosis Complex ◽

Osteoarticular Infections ◽

Study Investigator ◽

Mycobacteria Tuberculosis ◽

Culture Yield

Abstract Background Osteoarticular infections (OAI) account for 10-20% of extrapulmonary Mycobacteria tuberculosis (MTB) complex infections in children. Given the rarity of MTB OAI, the epidemiology, disease manifestations, and treatment are poorly characterized. We describe 21 children treated for MTB complex OAI over a 26-year period at a tertiary pediatric center in southern California. Methods We conducted a retrospective review of children diagnosed with MTB complex OAI and cared for between 31 Dec 1992 to 31 Dec 2018 at a single tertiary care pediatric hospital with close proximity to the United States-Mexico border. Results We identified 21 children with MTB complex OAI during the study period (Table 1). Concurrent pulmonary disease (4.8%), meningitis (9.5%), and intra-abdominal involvement (14.3%) were all observed. MTB complex was identified by culture from operative samples in 15/21 children (71.4%); 8/15 (51.3%) cultures were positive for Mycobacterium bovis. Of the eight cases of vertebral OAI (the most common site), one was culture-positive for M. bovis. Open bone biopsy was the most common procedure for procurement of a tissue sample and had the highest culture yield (Table 2). The median duration of antimicrobial therapy was 52 weeks (IQR 52-58). Successful completion of therapy was documented in 15 children (71.4%). Seven children (33.3%) experienced long term sequelae related to their infection. Table 1. Twenty-one children with Mycobacteria tuberculosis complex osteoarticular infections. Table 2. Surgical sample type and percent positivity. Conclusion Among the 21 children with MTB complex OAI assessed, 8 of 15 (53.3%) children with a positive tissue culture had M. bovis (intrinsically resistant to pyrazinamide), representing a higher percentage than in previous reports and potentially reflecting its presence in unpasteurized dairy products in the California-Baja region. Local epidemiological trends in endemic MTB complex species should be considered when evaluating and managing MTB complex OAI. Bone biopsy produced the highest culture yield in this study. Given the rarity of this disease, multicenter collaborative studies are needed to improve our understanding of the presentation and management of pediatric MTB complex OAI. Disclosures Vanessa Raabe, MD, MSc, Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, Editorial support)Sanofi (Scientific Research Study Investigator)

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Identifying Foot and Ankle Patients at Risk to Fall Based on Patient Reported Outcomes Assessments

Foot & Ankle Orthopaedics ◽

10.1177/2473011418s00026 ◽

2018 ◽

Vol 3 (3) ◽

pp. 2473011418S0002

Author(s):

Judith Baumhauer ◽

Jack Teitel ◽

Allison McIntyre ◽

David Mitten ◽

Jeff Houck

Keyword(s):

At Risk ◽

Effect Size ◽

Fall Risk ◽

Patient Reported Outcomes ◽

The United States ◽

Foot And Ankle ◽

Falls Risk ◽

Orthopaedic Patients ◽

Patient Reported ◽

Patients At Risk

Category: Other Introduction/Purpose: Each year approximately 30-40% of people over the age of 65 fall. Approximately one half of these falls result in an injury with the estimated annual direct medical costs of $30 billion. Pain, mobility issues, neuropathy and post-operative weight bearing limitations make foot and ankle patients particularly vulnerable to falls. Current approaches to determine at risk patients are cumbersome and time consuming requiring performance testing and “hands on” clinical assessment. The efficiency of obtaining PRO, such as PROMIS, in the clinical arena has been well documented. The purpose of this study is determine if patient reported outcomes (PROMIS) can identify orthopaedic and specifically foot and ankle patients at risk to fall. Methods: Prospective patient reported outcomes (PROMIS CAT physical function, pain interference and depression and CMS fall risk assessment questions) and patient demographics were collected for all patients at each clinic visit from an academic orthopaedic multi-specialty practice between January 2015 and November 2017. Standardized yes/no validated self-reported fall risk questions include: “Have you fallen in the last year?” and “Do you feel you are at risk of falling?” Histograms, t-tests, confidence intervals and effect size were used to determine the fall risk “YES” patients were different than the “NO” for ALL orthopaedic patients and specifically foot and ankle patients. Logistic Regression was used to determine if age, gender, height, weight, and PROMIS scales predicted self-reported falls risk. Results: 94,761 orthopaedic patients comprising 315,273 visits (44% male, mean age 53.7+/-17 years) and 13,720 foot/ankle patients comprising 33,480 visits (37% male, mean age 52.7+/-16.1 years) had complete data for analysis. Table 1 provides the means/SD/p-values/effect sizes for patient self-identifying at risk to fall stratified by PROMIS PF/ PI/Dep t-scores. Although all PROMIS scores demonstrated significant impairment between patients at risk designation (yes/no), PROMIS PF had the largest effect size for ALL Ortho and FOOT AND ANKLE patients (0.8 and 0.7 respectively). Patients who are at risk to fall have PROMIS PF t-scores >1.5 lower than the United States normative population while the patients not at risk are less <1 SD. In the adjusted regression models gender and PROMIS PF had the largest coefficients. Conclusion: Falls are a major threat to quality of life and independence yet prevention/treatment strategies are difficult to implement across a health system. There is also a tremendous societal cost with orthopaedic surgeons often the recipient of these debilitated patients. PROMIS assessments are part of the AOFAS OFAR initiative to track patient recovery with treatment and can additional be used to fulfill a quality indicator requirement by CMS. This study demonstrates these assessments (PROMIS threshold values) can also be linked to self-report falls risk (yes/no) and may identify patients at risk with no face to face time required from the provider.

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1157. Clinical Safety, Efficacy, and Pharmacokinetics of Fosmanogepix, a Novel First-in-class Antifungal, in Patients with Renal Insufficiency: Subset Analysis from a Phase 2 Candidemia Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1343 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S605-S605

Author(s):

Pierre Bulpa ◽

Galia Rahav ◽

Ilana Oren ◽

Mickaël Aoun ◽

George R Thompson ◽

...

Keyword(s):

Renal Function ◽

Renal Insufficiency ◽

Antifungal Agents ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Antifungal Treatment ◽

Successful Outcome ◽

Review Panel ◽

Study Investigator

Abstract Background Fosmanogepix (FMGX) is a first-in-class antifungal agent, with a unique MOA targeting the fungal enzyme Gwt1, and broad-spectrum activity against yeasts and molds, including fungi resistant to other antifungal agents. Patients with candidemia often have underlying renal insufficiency or are receiving medications that affect renal function. This analysis evaluated outcomes in patients with varying degrees of renal insufficiency. Methods This global, multicenter, open-label, non-comparative study evaluated the safety and efficacy of FMGX for first-line treatment of candidemia. Patients with a recent diagnosis of candidemia defined as positive blood culture for Candida spp within 96 hrs prior to study entry with ≤ 2 days of prior antifungal treatment were eligible, including those with renal insufficiency. Patients with neutropenia, C. krusei infection, deep-seated Candida infections or receiving hemodialysis were excluded. Subjects were treated with FMGX for up to 14 days: 1000 mg IV BID for 1 day, then 600 mg IV QD for at least 2 days, followed by either 600 mg IV QD or 700 mg PO QD. Patients requiring antifungal treatment beyond 14 days received fluconazole. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by an independent data review committee. Successful outcome was defined as survival with clearance of Candida from blood cultures with no additional antifungal treatment. Results 14/21 (66%) subjects had some degree of renal insufficiency: 7 had mild renal insufficiency (GFR:60-89), 5 had moderate renal insufficiency (GFR:30-59), and 2 had severe renal insufficiency (GFR:15-29). 12/14 (86%) completed study treatment, and treatment was successful at EOST in 12/14 (86%) subjects. Decline in renal function was not observed at EOST. 4 had worsening of renal function during the follow-up period; none required dialysis. Renal impairment did not increase exposure of FMGX. There were no treatment-related adverse events. Conclusion FMGX demonstrated high level treatment success with no evidence of drug-related nephrotoxicity, with no dose adjustments required. These preliminary data support the continued evaluation of FMGX in patients with candidemia and renal dysfunction as an alternative to potentially nephrotoxic antifungal agents. Disclosures Pierre Bulpa, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Mickaël Aoun, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Bart Jan Kullberg, MD, FRCP, FIDSA, Amplyx (Advisor or Review Panel member) Sara Barbat, BSN, RN, Amplyx Pharmaceuticals (Employee) Pamela Wedel, BSc, Amplyx Pharmaceuticals (Employee) Haran T. Schlamm, MD, Amplyx (Consultant) Michael Hodges, BSc. MD, Amplyx Pharmaceuticals Inc. (Employee)

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