1714. Influenza C Virus in U.S. Children with Acute Respiratory Infection 2016-2019

Abstract Background Influenza C virus (ICV) is associated with acute respiratory infection (ARI); however, the burden of ICV is not well-described. We sought to determine the burden and characteristics of ICV in a prospective, population-based cohort. Methods The study was conducted within the New Vaccine Surveillance Network (NVSN), a CDC-led, seven-site network that performs population-based surveillance for ARI in children < 5 years. Nasal/throat swabs were collected from emergency department (ED) or inpatient children with ARI, or healthy controls in clinic, between 12/05/2016-10/31/2019 and tested by real-time RT-PCR for ICV and other respiratory viruses. Preliminary data were extracted and demographic/clinical features of ICV+ cases analyzed. We sequenced the hemagglutinin-esterase (HE) gene from ICV+ Pittsburgh samples. Results Among 19,321 children with ARI or healthy controls enrolled and tested for ICV from 2016-2019, 115/17,668 (0.7%) ARI cases and 8/1653 (0.5%) healthy controls tested positive for ICV. The median age of ICV+ ARI subjects was 19 months (IQR 10,46) and 81(70%) were ≤36 months. 42.6% (49) were white, 33.9% (39) black, and 16.5% (19) Hispanic, with the remainder Asian or unknown; 56.5% (62) attended daycare. Among ICV+ ARI cases, 67.8% (78) had fever, 94.8% (109) cough, and 60.8% (70) wheezing. 45.2% (52) ICV+ cases occurred in 2016-17, 6.5% (8) in 2017-2018, and 47.8% (55) in 2018-19 (Table). 40% (46) of ICV+ cases were seen in the ED, while the remainder were inpatients. Median length of stay was 2d (IQR,1-3) with 15 admitted to ICU. 67.8% (78/115) ARI cases had 1 or 2 co-detected pathogens, with rhinovirus (26), respiratory syncytial virus (26), and adenovirus (14) most frequently co-detected. ARI symptoms including fever, myalgias, chills, and wheezing did not differ significantly between coinfected subjects and those who were only ICV+. HE sequences were in the two currently circulating Kanagawa and Sao Paulo lineages. ICV+ Cases by Site and Year Conclusion ICV was an uncommon cause of ARI symptoms leading to healthcare encounters in young children. The prevalence varied year-to-year and between different geographic regions. Most children infected with ICV were ≤3 years old and had co-detected pathogens. ICV was similarly rarely detected in healthy controls. Disclosures Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial) 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)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member)

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78. Acute Respiratory Illnesses in Children During the sars-cov-2 Pandemic: A Prospective Multicenter Surveillance Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.388 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S170-S171

Author(s):

Zaid Haddadin ◽

Jennifer E Schuster ◽

Andrew J Spieker ◽

Herdi Kurnia Rahman ◽

Laura S Stewart ◽

...

Keyword(s):

Research Study ◽

Vaccine Trial ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Respiratory Illnesses ◽

Study Investigator ◽

Support Research ◽

Research Grant

Abstract Background A state of emergency was declared in the United States (US) on March 13, 2020 in response to the SARS-CoV-2 pandemic. Healthcare providers had to alter practice patterns and research priorities. We assessed the frequency of acute respiratory illnesses (ARI) in children, notably those due to respiratory syncytial virus (RSV) and influenza, before and during the pandemic. Methods We conducted multi-center active prospective ARI surveillance in children as part of the New Vaccine Surveillance Network. Children < 18 years with fever and/or respiratory symptoms were enrolled in emergency department and inpatient settings at seven US medical centers over four respiratory seasons during 2016–2020 (Fig 1). Pandemic-related restrictions to patient access limited enrollment in some sites beginning March 2020. Respiratory specimens were collected and tested at each site for RSV and influenza by qRT-PCR. Data were analyzed by calendar weeks. We compared the cumulative proportions of RSV and influenza detection after week 13 in 2020 to the previous seasons using Fisher’s exact test. Figure 1. Numbers of Eligible and Enrolled Acute Respiratory Illness Cases, and Proportions of RSV and Influenza Detection by Week, Stratified by Study Season Results Of 44,247 eligible children, 25,375 (57%) were enrolled and tested for RSV and/or influenza. A total of 6351/25375 (25%) and 3446/25372 (14%) children were RSV and influenza-positive over the four seasons, respectively. In 2020, we noted a rapid drop in eligible and enrolled ARI subjects after weeks 11–13 (Fig 1). During weeks 13–18 in 2016–2019, the three-year average of eligible and enrolled subjects was 1802 and 978, respectively. However, over the same period in 2020, there were 675 eligible and 278 enrolled subjects, representing declines of 62.5% and 71.6% respectively (Fig 1). In 2020, there were no RSV or influenza cases detected in weeks 15–18, and the cumulative proportions of RSV and influenza detection after week 13 were lower compared to previous seasons (p< 0.001) (Figs 1 and 2). Figure 2. Cumulative Proportions of Weekly RSV and Influenza Detection by Study Season Conclusion There was a considerable decline in ARI visits and the proportion of RSV and influenza detection across seven distinct geographic sites during the pandemic compared with previous seasons. These findings might be attributable to social distancing measures to lessen the spread of SARS-CoV-2, changes in healthcare-seeking behaviors, and limited access to medical care. Disclosures Zaid Haddadin, MD, CDC (Grant/Research Support, Research Grant or Support)Quidel Corporation (Grant/Research Support, Research Grant or Support)sanofi pasteur (Grant/Research Support, Research Grant or Support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member) Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial) Janet A. Englund, MD, AstraZeneca (Scientific Research Study Investigator)GSK group of companies (Scientific Research Study Investigator)Meissa vaccines (Consultant)Merck (Scientific Research Study Investigator)Sanofi Pasteur (Consultant) 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)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1532 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S757-S758

Author(s):

Olivia D Reese ◽

Ashley Tippett ◽

Laila Hussaini ◽

Luis Salazar ◽

Megan Taylor ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Healthy Controls ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Tract Infections ◽

The Impact ◽

Research Grant

Abstract 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)

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LB13. The Efficacy and Impact in Heathy Infants of Nirsevimab on Medically Attended RSV Lower Respiratory Tract Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1649 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S811-S812

Author(s):

Laura Hammitt ◽

Ron Dagan ◽

Yuan Yuan ◽

Manuel Baca Cots ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Term Infants ◽

Study Investigator ◽

Support Research ◽

Research Grant

Abstract Background Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in infants. Nirsevimab is a single-dose monoclonal antibody with extended half-life that was shown to protect preterm infants 29 to < 35 weeks gestation against RSV LRTI. However, most medically attended (MA) cases occur in otherwise healthy, term infants for whom there is currently no effective RSV prevention strategy. We report the primary analysis of efficacy and safety, along with the impact of nirsevimab in late preterm and term infants (≥ 35 weeks gestation) in the phase 3 MELODY study (NCT03979313). Methods Infants were randomized 2:1 to receive one intramuscular injection of nirsevimab (50 mg if < 5 kg; 100 mg if ≥ 5 kg at dosing) or placebo entering their first RSV season. The primary endpoint was the incidence of MA RSV LRTI over 150 days postdose. Cases met predefined clinical criteria of disease severity and were confirmed by real-time reverse-transcriptase PCR. Safety was evaluated through 360 days postdose. Enrollment started on 23 July 2019 and was suspended following the declaration of the COVID-19 pandemic by the WHO on 11 March 2020. Results Overall, 1490 infants were randomized and included in the intent-to-treat population; 1465 (98%) completed the 150-day efficacy follow-up, and 1367 (92%) completed the 360-day safety follow-up. The incidence of MA RSV LRTI was 1.2% (n=12/994) in the nirsevimab group and 5.0% (n=25/496) in the placebo group, giving nirsevimab an efficacy of 74.5% (95% confidence interval [CI]: 49.6, 87.1; p< 0.0001). Nirsevimab averted 93.6 (95% CI 63.0, 124.0) MA LRTIs per 1000 infants dosed. Nirsevimab was well tolerated, with similar rates of adverse events (87.4% nirsevimab; 86.8% placebo) and serious adverse events (6.8% nirsevimab; 7.3% placebo) between groups. Conclusion In this phase 3 study, a single dose of nirsevimab protected late preterm and term infants against MA RSV LRTI over an RSV season with a favorable safety profile. Approximately 11 infants need to be immunized to prevent 1 case of LRTI; nirsevimab has the potential to be an important intervention to reduce the burden of RSV LRTI in healthy infants. Disclosures Laura Hammitt, MD, MedImmune (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Novavax (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Laura Hammitt, MD, MedImmune (Individual(s) Involved: Self): Grant/Research Support, Research grant to my institution; Merck (Individual(s) Involved: Self): Grant/Research Support, Research grant to my institution; Pfizer (Individual(s) Involved: Self): Grant/Research Support, Research grant to my institution Ron Dagan, MD, Medimmune/AstraZeneca (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau) Yuan Yuan, PhD, AstraZeneca (Employee, Shareholder) Shabhir A. Mahdi, PhD, BMGF (Research Grant or Support)EDCTP (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melody (Research Grant or Support)Minervax (Research Grant or Support)Novavax (Research Grant or Support)SAMRC (Research Grant or Support) William J. Muller, MD, PhD, Ansun (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)AstraZeneca (Scientific Research Study Investigator)Genentech (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Janssen (Scientific Research Study Investigator)Karius (Scientific Research Study Investigator)Melinta (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)Nabriva (Scientific Research Study Investigator)Seqirus (Scientific Research Study Investigator)Tetraphase (Scientific Research Study Investigator) William J. Muller, MD, PhD, Ansun (Individual(s) Involved: Self): Grant/Research Support; Astellas (Individual(s) Involved: Self): Research Grant or Support; AstraZeneca (Individual(s) Involved: Self): Grant/Research Support; BD (Individual(s) Involved: Self): Research Grant or Support; Eli Lilly (Individual(s) Involved: Self): Grant/Research Support; Gilead (Individual(s) Involved: Self): Grant/Research Support; Karius, Inc. (Individual(s) Involved: Self): Grant/Research Support, Scientific Research Study Investigator; Melinta (Individual(s) Involved: Self): Grant/Research Support; Merck (Individual(s) Involved: Self): Grant/Research Support; Moderna (Individual(s) Involved: Self): Grant/Research Support; Nabriva (Individual(s) Involved: Self): Grant/Research Support; Seqirus (Individual(s) Involved: Self): Consultant; Tetraphase (Individual(s) Involved: Self): Grant/Research Support Heather J. Zar, PhD, AstraZeneca (Grant/Research Support)Novavax (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member) Dennis Brooks, MD, AstraZeneca (Employee) Amy Grenham, MSc, AstraZeneca (Employee, Shareholder) Ulrika Wählby Hamrén, PhD, AstraZeneca R&D (Employee, Shareholder) Vaishali S. Mankad, MD, AstraZeneca (Employee) Therese Takas, BSc, AstraZeneca (Employee, Other Financial or Material Support, Own stock in AstraZeneca) Jon Heinrichs, PhD, AstraZeneca (Shareholder)Bristol Myers Squibb (Shareholder)J&J (Shareholder)Merck (Shareholder)Organon (Shareholder)Procter & Gamble (Shareholder)Sanofi (Shareholder)Sanofi Pasteur (Employee) Amanda Leach, MRCPCH, AstraZeneca (Employee, Shareholder) M. Pamela Griffin, MD, AstraZeneca (Employee) Tonya L. Villafana, PhD, AstraZeneca (Employee)

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354. SARS-CoV-2 Viral Viability Culture and Sequencing from Immunocompromised Patients with Persistently Positive SARS-CoV-2 PCR Results

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.555 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S281-S281

Author(s):

Abby Sung ◽

Adam Bailey ◽

Meghan Wallace ◽

Henry B Stewart ◽

David McDonald ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator ◽

Jewish Hospital ◽

Support Research ◽

Research Grant

Abstract Background Immunocompromised (IC) patients (pts) can have prolonged SARS-CoV-2 PCR positivity, even after resolution of COVID-19 symptoms. This study aimed to determine if viable virus could be detected in samples collected > 21 days after an initial positive (pos) SARS-CoV-2 PCR in IC pts. Methods We obtained 20 remnant SARS-CoV-2 PCR pos nasopharyngeal swabs from IC pts (bone marrow or solid organ transplant, high dose steroids, immunosuppressive medications) with a pos repeat PCR within the previous 30 days. The repeat specimens were cultured on Vero-hACE2-TMPRSS2 cells and incubated for 96 hours to assess viral viability. Viable RNA and infectious virus in the cultured cells were measured by qPCR and infectious plaque assays. RNA sequencing was performed on a HiSeq platform (Illumina). Samples also underwent SARS-CoV-2 antigen (Ag) testing (BD Veritor). Clinical data were extracted from the electronic health record by chart review. Results Pt characteristics are in Table 1. Viral cultures from the repeat specimen were negative (neg) for 18 pts and pos for 2 (Table 2). Pt 1 is a 60M treated with obinatuzumab 19 days prior to his first pos PCR test, with repeat specimen collected 21 days later (cycle threshold (Ct) not available). Pt 1 had a low viral titer (27 PFU/mL) & a D614G mutation on sequencing. Pt 2 is a 75M treated with rituximab 10 days prior to his first pos PCR test, with repeat specimen collected 23 days later (Ct 27.56/27.74). Pt 2 had a high viral titer (2e6 PFU/mL) and D614G, S98F, and S813I mutations. Demographics of Study Population (N=20) Characteristics of patients with a positive SARS-CoV-2 viral culture Conclusion 90% of specimens collected > 21 days after an initial pos SARS-CoV-2 PCR did not have viable virus detected on their repeat specimen. The 2 pts with pos viral cultures had active hematologic malignancies treated with an anti-CD20 mAb at the time of COVID-19 diagnosis. One pt had a high concentration of active, viable virus. No known variants of concern were noted in this cohort, collected in Q2 2020, though prolonged replication is a risk for variant development. Further data are needed about risk factors for persistent viable viral shedding & methods to prevent transmission of viable virus from IC hosts. Disclosures Victoria J. Fraser, MD, CDC Epicenters (Grant/Research Support)Cigna/Express Scripts (Other Financial or Material Support, Spouse is Chief Clinical Officer)Doris Duke Fund to Retain Clinical Scientists (Grant/Research Support, Research Grant or Support)Foundation for Barnes-Jewish Hospital (Grant/Research Support, Research Grant or Support)NIH (Grant/Research Support, Research Grant or Support) Victoria J. Fraser, MD, Centers for Disease Control and Prevention (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; Cigna/Express Scripts (Individual(s) Involved: Spouse/Partner): Employee; Doris Duke Charitable Foundation (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; National Institutes of Health (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; The Foundation for Barnes-Jewish Hospital (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Michael S. Diamond, MD, PhD, Carnival Corporation (Consultant)Emergent BioSolutions (Grant/Research Support)Fortress Biotech (Consultant)Immunome (Advisor or Review Panel member)Inbios (Consultant)Moderna (Grant/Research Support, Advisor or Review Panel member)Vir Biotechnology (Consultant, Grant/Research Support) Carey-Ann Burnham, PhD, BioFire (Grant/Research Support, Other Financial or Material Support)bioMerieux (Grant/Research Support)Cepheid (Consultant, Grant/Research Support)Luminex (Grant/Research Support)Roche (Other Financial or Material Support) Carey-Ann Burnham, PhD, BioFire (Individual(s) Involved: Self): Grant/Research Support; bioMerieux (Individual(s) Involved: Self): Grant/Research Support, Scientific Research Study Investigator, Speakers’ bureau; Cepheid (Individual(s) Involved: Self): Consultant, Grant/Research Support, Scientific Research Study Investigator; Luminex (Individual(s) Involved: Self): Scientific Research Study Investigator Hilary Babcock, MD, MPH, FIDSA, FSHEA, Nothing to disclose

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1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1290 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S582-S583

Author(s):

Eleni Karantoni ◽

Yiqi Su ◽

Anat Stern ◽

Phaedon D Zavras ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

T Cell ◽

Panel Member ◽

Multivariable Model ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Advisory Boards ◽

Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

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1475. Impact of a Routine Infant PCV Program on the Serotype Distribution of Episodes of Invasive Pneumococcal Disease (IPD) and Non-bacteremic Pneumococcal Pneumonia in Adults

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1656 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S739-S739

Author(s):

Allison McGeer

Keyword(s):

Pneumococcal Pneumonia ◽

Herd Immunity ◽

Panel Member ◽

Population Based ◽

Review Panel ◽

Vaccine Type ◽

Bacteremic Pneumococcal Pneumonia ◽

Type Strains ◽

Routine Infant ◽

Research Grant

Abstract Background Herd immunity from pediatric pneumococcal conjugate vaccine (PCV) programs has resulted in substantial reductions in IPD due to PCV serotypes (ST). We assessed whether similar changes in ST distribution occur in non-bacteremic pneumococcal pneumonia (NBPP). Methods The Toronto Invasive Bacterial Diseases Network performs population-based surveillance for IPD and hospitalized, culture-confirmed NBPP in Toronto/Peel Region, Canada (Pop 4.5M). Patient data are collected by interview/chart review; illness associated with respiratory isolates is categorized using Musher criteria. Results Since 2002, 6627 episodes of IPD, and 7323 non-bacteremic episodes with a respiratory isolate of S. pneumoniae (2180 meeting modified Musher criteria for NBPP) have occurred in adults. Distributions of vaccine-type serotypes in IPD and NBPP pre-PCV7 (2002-2004), post-PCV7 (2006-2009) and late post-PCV13 (2014-2019) are shown in the Figure. There were no significant changes in distribution of vaccine serotype groups from 2014-2019 in IPD or NBPP. From 2014-2019, serotypes included in PCV13 and PCV20 were associated with 33% and 59% of IPD cases, and 29% and 49% of NBPP cases in adults.. Figure. distribution of serotype groups included in different pneumococcal vaccines in cases of IPD and non-bacteremic pneumonia Conclusion Eight years post routine infant PCV13 implementation, PCV13 type IPD and NBPP persists in adults. The distribution of vaccine-type strains is similar in IPD and NBPP; although non-vaccine-type strains are more common in NBPP. Disclosures Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)

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108. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.418 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S183-S183

Author(s):

Rajesh Gandhi ◽

Joshua Cyktor ◽

Ronald Bosch ◽

Hanna Mar ◽

Gregory Laird ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Panel Member ◽

Plasma Viremia ◽

Research Support ◽

Review Panel ◽

Proviral Dna ◽

Hiv 1 ◽

Over Time ◽

Residual Plasma Viremia ◽

Research Grant

Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well-defined in people on ART. Methods We separately quantified intact and defective proviruses (using an intact proviral DNA assay), residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Longitudinal measurements were done at three timepoints: timepoint 1 was a median of 7.1 years on ART; timepoint 2 was a median of 3.7 years later; timepoint 3 was a median of 5.5 years after timepoint 1 and a median 12 years after starting ART (Figure 1). Figure 1: Study timepoints Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life 7.1 years; 95% confidence interval [CI], 3.9, 18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6, 75). When we evaluated the change in proviral DNA per year, intact proviral DNA declined significantly more (p< 0.001) than defective proviral DNA (the latter did not change) (Figure 2). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART timepoint to about 5% at the last timepoint (Figure 3). At timepoint 1, intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Figure 2: Percent change in HIV-1 proviral DNA per year Figure 3: Total HIV-1 proviruses (grey bars) and the percentage of intact proviruses (red lines, displaying median, Q1, Q3) by timepoint. Conclusion Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion. Disclosures Rajesh Gandhi, MD, Merck (Advisor or Review Panel member) Gregory Laird, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Albine Martin, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Bernard Macatangay, MD, Gilead (Grant/Research Support) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV Healthcare (Consultant, Research Grant or Support) Janet Siliciano, PhD, Gilead (Advisor or Review Panel member)US Military HIV Research Program (Advisor or Review Panel member) John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant)

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120. An open-label comparative trial of SUBA-itraconazole (SUBA) versus conventional itraconazole (c-itra) for treatment of proven and probable endemic mycoses (MSG-15): a pharmacokinetic (PK) and adverse Event (AE) analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.120 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S72-S72

Author(s):

Peter G Pappas ◽

Andrej Spec ◽

Marisa Miceli ◽

Gerald McGwin ◽

Rachel McMullen ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Serum Levels ◽

Research Support ◽

Open Label ◽

Review Panel ◽

Study Investigator ◽

Endemic Mycoses ◽

Research Grant

Abstract Background C-itra is the drug of choice for treatment of most non-CNS, non-life-threatening forms of endemic mycoses (EM), including histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis and talaromycosis. SUBA represents a new formulation of itraconazole that utilizes nanotechnology to improve bioavailability when administered orally. SUBA is formulated as nanoparticles allowing for absorption in the small bowel while not relying on gastric acidity for optimal absorption. MSG-15 is an open-label, comparative clinical trial comparing SUBA to c-itra for the treatment of EM. Herein we report the final PK and AE profiles of these two compounds. Methods Subjects with proven and probable EM were eligible this open-label comparative study. The protocol allowed up to 14 d of prior therapy with any antifungal for this episode of EM. Subjects were randomized to receive either SUBA 130 mg po bid or c-itra 200 mg po bid for up to 6 months. Follow up occurred at 7, 14, 28, 42, 84 and 180 d post-enrollment. PK samples were obtained at 7, 14, and 42 d. Clinical assessment, including symptom assessment, AEs, overall drug tolerance, and quality of life were assessed at each visit. We used descriptive statistics for this analysis. Results 89 subjects with EM entered the trial, including 43 on SUBA and 46 on c-itra. We measured PK serum levels of itra and hydroxyl-itra at days 7, 14, and 42 and these data are depicted in Figures 1-3. There were no significant differences in these levels, including combined itra/hydroxyl-itra levels, among the two study arms. AUC for itra and hydroxyl-itra were similar for both arms. AEs as assessed at each study evaluation were also quite similar among the two study arms. Overall, any AE occurred in 74% vs 85% of SUBA and c-itra recipients, respectively (NS). Drug-related AEs occurred in 35% vs 41% of SUBA and itra recipients, respectively (NS). Most common drug-related AEs included cardiovascular (edema and hypertension), nausea and loss of appetite. Combined Itraconazole and Hydroxy-itraconazole Concentration Over Time Conclusion Compared to c-itra, SUBA demonstrates almost identical serum levels despite being dosed at roughly 60% standard dosing for c-itra (130 mg po bid vs 200 mg po bid). SUBA is slightly better tolerated than c-itra, although the specific AEs are similar. Disclosures Peter G. Pappas, MD, Astellas (Research Grant or Support)Cidara (Research Grant or Support)F2G (Consultant)Matinas (Consultant, Scientific Research Study Investigator)Mayne Pharma (Research Grant or Support)Scynexis (Research Grant or Support) Andrej Spec, MD, MSCI, Mayne Pharma (Grant/Research Support) Marisa Miceli, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) George R. R. Thompson III, III, MD, Amplyx (Consultant, Grant/Research Support)Appili (Consultant)Astellas (Consultant, Grant/Research Support)Avir (Grant/Research Support)Cidara (Consultant, Grant/Research Support)F2G (Consultant, Grant/Research Support)Mayne (Consultant, Grant/Research Support)Merck (Scientific Research Study Investigator)Pfizer (Advisor or Review Panel member)

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548. Baseline characteristics associated with clinical improvement and mortality in hospitalized patients with moderate COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.742 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S340-S340

Author(s):

Antonella Castagna ◽

David Shu Cheong Hui ◽

Kathleen M Mullane ◽

Mamta Jain ◽

...

Keyword(s):

Clinical Improvement ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Hospitalized Patients ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Baseline Characteristics ◽

Research Grant

Abstract Background Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report baseline characteristics associated with clinical improvement at day (d) 14. Methods We enrolled hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation >94% on room air, and radiological evidence of pneumonia. Patients were randomized 1:1:1 to receive 5d or 10d of intravenous RDV once daily plus standard of care (SoC), or SoC only. For this analysis, patients were followed through discharge, d14, or death. Baseline demographic and disease characteristics associated with clinical improvement in oxygen support (≥2-point improvement on a 7-category ordinal scale ranging from discharge to death) were evaluated using multivariable logistic regression methods. Results 584 patients were randomized and treated (5/10d RDV, n=384; SoC: n=200). 159 (27%) were ≥65y, 227 (39%) female, 328 (61%) white, 102 (19%) Asian, and 99 (19%) Black. 252 participants (43%) were enrolled in Europe, 260 (45%) North America (NA), and 72 (12%) in Asia. Most patients (483 [83%]) were not on supplemental oxygen but required medical care at baseline. In a multivariable model, 5/10d RDV was significantly positively associated with clinical improvement (adjusted odds ratio [OR] 1.69, 95% CI: 1.08, 2.65; p=0.0226). Significant covariables positively associated with clinical improvement included age < 65y (p< 0.0001) and region of treatment (Europe and NA vs Asia, p< 0.0001 each; Table); other examined factors were not significantly associated with clinical improvement, including gender, race, ethnicity, baseline oxygen support, duration of symptoms and hospitalization, obesity, and baseline transaminase levels. Table 1. Conclusion In moderate COVID-19 patients, after adjusting for treatment arm, age < 65y and region (NA vs Asia; Europe vs Asia) were associated with higher rates of clinical improvement. These observations recapitulate younger age as positive prognostic factor, and highlight the differences in the impact of the pandemic globally. Disclosures Antonella Castagna, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) David Shu Cheong Hui, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Kathleen M. Mullane, DO, PharmD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator) Mamta Jain, MD, Gilead Sciences Inc. (Scientific Research Study Investigator, Research Grant or Support)GlaxoSmithKline (Advisor or Review Panel member)Janssen (Research Grant or Support)Merck (Research Grant or Support) Massimo Galli, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Personal fees) Shan-Chwen Chang, MD, PhD, Gilead Sciences Inc. (Scientific Research Study Investigator) Robert H. Hyland, MD, Gilead Sciences Inc. (Employee, Shareholder) Devi SenGupta, MD, Gilead Sciences Inc. (Employee, Shareholder) Huyen Cao, MD, Gilead Sciences Inc. (Employee, Shareholder) Hailin Huang, PhD, Gilead Sciences Inc. (Employee, Shareholder) Anand Chokkalingam, PhD, Gilead Sciences (Employee) Anu Osinusi, MD, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Christoph Lübbert, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) David Chien Boon Lye, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) David Chien Boon Lye, MD, NO DISCLOSURE DATA Judith A. Aberg, MD, Theratechnology (Consultant) Enrique Navas Elorza, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Karen T. Tashima, MD, Bristol-Myers Squibb (Research Grant or Support)Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator)GlaxoSmithKline (Research Grant or Support)Merck (Research Grant or Support)Tibotec (Research Grant or Support)Viiv Healthcare (Research Grant or Support) Mark McPhail, MD, Gilead Sciences Inc. (Scientific Research Study Investigator)

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1211. Incidence of All-Cause Community-Acquired Pneumonia in Ontario and British Columbia, Canada, 2002-2018; a Canadian Immunization Research Network (CIRN) study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1403 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S695-S696

Author(s):

Sharifa Nasreen ◽

John Wang ◽

Jeffrey Kwong ◽

Natasha S Crowcroft ◽

Manish Sadarangani ◽

...

Keyword(s):

Older Adults ◽

British Columbia ◽

Pneumococcal Conjugate Vaccine ◽

Age Groups ◽

Panel Member ◽

Community Acquired Pneumonia ◽

Annual Incidence ◽

Research Support ◽

Review Panel ◽

Research Grant

Abstract Background Community-acquired pneumonia (CAP) causes substantial morbidity and mortality. There is a lack of data on the comprehensive burden of CAP across the life span in Canada. We estimated the incidence of all-cause CAP in all age groups in Ontario and British Columbia (BC), Canada. Methods We identified hospitalized and outpatient CAP episodes from the Discharge Abstract Database (DAD) and physician billing claims databases (Ontario Health Insurance Plan in Ontario and Medical Services Plan in BC) in both provinces. The National Ambulatory Care Reporting System was used to identify CAP episodes from emergency department visits in Ontario. CAP recorded with a primary or secondary diagnosis was identified using International Classification of Diseases 9 (480–486, 510, 513) and 10 (J10.0, J11.0, J12–J18, J86.9, J85.1) codes. We estimated the age and sex adjusted annual incidence of CAP overall, and by age groups (0–4, 5–17, 18–39, 40–64, 65–74, 75–84 and ≥85 years) according to routine childhood pneumococcal conjugate vaccine (PCV) immunization periods from 2005–2018 in Ontario and from 2002–2018 in BC. Poisson regression models were fitted with population denominators from Statistics Canada to estimate the incidence rates. Results Ontario had 3,607,186 CAP episodes from 2005–2015 with a mean annual incidence of 2,801 (95% confidence interval [CI]: 2,748, 2,854) per 100,000 population; incidence declined from 3,077/100,000 in 2005 to 2,604/100,000 in 2010 before increasing to 2,843/100,000 in 2018. BC had 1,146,172 CAP episodes from 2002–2008, with a mean annual incidence of 2,146 (95% CI: 2105, 2189); the incidence increased from 2,005 /100,000 in 2002 to 2,199/100,000 in 2018. A high incidence of CAP was observed in children aged 0–4 years and older adults, particularly in adults aged ≥85 years in both provinces across all PCV program periods (Figure 1). Figure 1: Age group-specific incidence of all-cause community-acquired pneumonia according to childhood pneumococcal conjugate vaccine (PCV) program periods in Ontario (PCV7 [1 Jan 2005–30 Sep 2009]), PCV10 [1 Oct 2009–31 Oct 2010] and PCV13 [1 Nov 2010–31 Dec 2018]) and British Columbia (PCV7 [1 Sep 2003–31 May 2010] and PCV13 [1 Jun 2010–31 Dec 2018]), Canada Conclusion CAP continues to be a public health burden in Canada despite publicly funded pneumococcal vaccination programs. Ontario seems to have higher CAP burden than British Columbia that warrants further investigation. The youngest cohort of children and older adults contribute significantly to the CAP burden. Disclosures Manish Sadarangani, BM BCh, DPhil, GlaxoSmithKline (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)Seqirus (Grant/Research Support)Symvivo (Grant/Research Support)VBI Vaccines (Research Grant or Support) Allison McGeer, MSc,MD,FRCPC,FSHEA, GlaxoSmithKline (Advisor or Review Panel member)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) James D. Kellner, MD, FRCPC, FIDSA, Pfizer, Merck, GSK, Moderna (Grant/Research Support) Shaun Morris, MD, MPH, DTM&H, FRCPC, FAAP, GSK (Speaker’s Bureau)Pfizer (Advisor or Review Panel member)Pfizer (Grant/Research Support) Shaza A. Fadel, PhD MPH, Merck (Other Financial or Material Support, Salary is paid by the University of Toronto via a donation by Merck to the Centre for Vaccine Preventable Diseases to support educational and operational activities.) Fawziah Marra, BSc(Pharm), PharmD, Pfizer Canada (Research Grant or Support)

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