Background: In 2014, the Advisory Committee on Immunization Practices recommended routine use of the 13valent pneumococcal conjugate vaccine (PCV13) in adults age > 65 years. Incidence of most PCV13-serotype cases declined, however serotype 3 cases have persisted. We estimated PCV13 vaccine effectiveness (VE) against PCV13-serotypes and serotype 3 invasive pneumococcal disease (IPD) among Kaiser Permanente Northern California (KPNC) adults. Methods: This observational study included adults >65 years between September 1, 2014-December 31, 2020. We used active laboratory-based surveillance to identify and serotype all Streptococcus pneumoniae isolates obtained from normally-sterile sites. We estimated the odds ratio (OR) of vaccine-type IPD using conditional logistic regression stratified by age and calendar day, adjusting for sex, age, race, ethnicity, influenza vaccine receipt, 23-valent pneumococcal polysaccharide vaccine receipt since age 65, pneumonia risk factors, healthcare utilization, and KPNC service area. We estimated VEAdjusted as (1-ORAdjusted) x 100 %. Results: There were 610,576 adults >65 years in the study population. By the end of the study period, PCV13 coverage was nearly 80 %. There were 307 IPD cases during the study period, of which 98 (31.9 %) were serotype 3. PCV13 was associated with a VEAdjusted of 61.5% (95% CI: 36.2, 76.7; p < 0.001) against PCV13serotype IPD and 46.3 % (95 % CI: -2.4, 77.9; p = 0.06) against serotype 3 IPD. Conclusions: PCV13 vaccination protected adults >65 years against IPD due to PCV13 serotypes. Continued surveillance will be critical in the >65-year-old population to assess the impact of higher valent PCVs on IPD serotype distribution, including individual serotypes such as serotype 3.

BACKGROUND:In the United States, the invasive pneumococcal disease incidence in Indigenous populations is higher than in the general population. Molecular detection and/or specimen sampling from multiple body sites could enhance our understanding of pneumococcal carriage, a prerequisite for disease. METHODS:Persons aged <5 and ≥18 years from the Navajo Nation and White Mountain Apache Tribal lands were enrolled in an observational carriage study from October 2015 through September 2017. Swabs from the nasopharynx (all participants) and oropharynx (adults only) were collected and tested by enriched culture or molecular methods (lytA and piaB polymerase chain reaction [PCR]). Cultured Streptococcus pneumoniae was serotyped by sequencing. PCR-positive samples were serotyped by 13-valent pneumococcal conjugate vaccine (PCV13)-type PCR and TaqMan array card PCR. RESULTS:An overall 1503 participants were enrolled (age <5 years, n = 600; ≥18 years, n = 903). Among children, pneumococcal positivity was similar by culture (49.5%) and PCR (50.8%); PCV13-type carriage was 8.0% by any method. Among adults, oropharyngeal swab positivity by PCR was 18.5%, an increase when compared with cultured oropharyngeal swabs (0.6%) and nasopharyngeal swabs by culture (7.9%) or PCR (5.3%); PCV13-type carriage by any sample or method was 8.0%. CONCLUSIONS:PCV13-type carriage persists in Indigenous populations. Use of molecular methods and oropharyngeal swabs for adults increased carriage prevalence estimates.

Background:Healthcare workers are at increased risk of exposure to respiratory pathogens including Streptococcus pneumoniae (pneumococcus). While little asymptomatic carriage has been reported in young-to-middle-aged adults, this may be due to nonsensitive diagnostic methods. The aim of the current study was to investigate the rates of pneumococcal carriage in a large cohort of healthcare workers, using saliva as a respiratory specimen. Methods:We evaluated pneumococcal carriage in convenience samples of saliva, self-collected from asymptomatic healthcare workers (Connecticut, USA) who were testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 30 March to 11 June 2020. DNA extracted from the culture-enriched saliva was later tested using quantitative polymerase chain reaction for piaB, lytA, and serotype. Saliva samples were considered positive for pneumococcus when the piaB cycle threshold value was <40. Results:Study participants were 22-74 years old (mean age, 38.5 years), 75% female, 75% white, and with occupations including registered nurses (48%), medical doctors (23%), and patient care assistants (5%). Overall, 138 of 1241 samples (11%) from 86 of 392 individuals (21%) tested piaB positive at some point during the 4-month study period, with 28 (33%) colonized individuals positive at multiple time points. Carriers reflected the overall study population. No significant demographic characteristics were associated with detection of pneumococcus. Colonized individuals primarily carried serotypes 19F (25.6%) and 3 (12.8%). Conclusions:During a period of mandatory masking, we identified a cumulative pneumococcal carriage prevalence of 21% among healthcare workers. This study highlights that healthcare workers may act as unrecognized reservoirs of pneumococcus in the population. Despite long-standing pediatric immunization programs, vaccine-targeted serotypes continue to be prevalent among the adult population.

ABSTRACT Background Important questions remain about the sources of transmission of pneumococcus to older adults in the community. This is a critical question for understanding the potential indirect effects of using pneumococcal conjugate vaccines (PCVs) in children and older adults. For non-institutionalized individuals, the most likely source of adult-to-adult transmission is in the household. The goal of this study was to characterize the dynamics and risk factors for acquisition of pneumococcus in older adults. Methods We designed a longitudinal study to sample adults >60 years of age living in the same household (New Haven, CT, USA), and without younger contacts residing in the household. Saliva samples and questionnaires regarding social behaviors and health status were obtained every 2 weeks for a period of 10 weeks. DNA extracted from culture-enriched saliva was tested using qPCR for pneumococcus genes piaB and lytA . Results Across two study seasons (November 2020-August 2021, November 2021-September 2022), 121 individuals from 61 households were followed for 6 study visits; 62 individuals were enrolled in both seasons. Overall, 52/1088 (4.8%) samples tested positive for pneumococcus based on piaB , with 27/121 (22.3%) individuals colonized on at least one time point. Several individuals were colonized at multiple timepoints including two individuals who were colonized throughout the 10-week sampling period; two others were colonized at 5 of 6 time points. In 5 instances, both members of the household were carriers in the same season, though not necessarily at the same time point. Pneumococcal carriage was substantially higher among individuals who had contact with children (10.0% vs 1.6%). Participants who reported recent contact with <5-year-olds and 5-9-year-olds had particularly elevated prevalence (13.8%; 14.1%, respectively). Conclusions Contact with young children was the most important factor that influenced pneumococcal acquisition rates. While there were several instances where both adult household members were colonized at the same time or at sequential visits, these individuals also both typically had contact with children.

Abstract Background Nirmatrelvir-ritonavir (NMV-r) is an oral antiviral medication used for the treatment of mild-to-moderate COVID-19 in patients aged 12 years or older at high risk of progression to severe disease and hospitalization. Following real-world utilization beginning in late 2021, millions of patients worldwide have been treated with NMV-r and many studies have described outcomes following treatment. This systematic literature review (SLR) was conducted to summarize the real-world clinical impact of NMV-r to inform healthcare decision-making. Methods Real-world studies of NMV-r use available in English, with ≥5 subjects, and reporting on hospitalization and/or mortality outcomes were identified from Embase, PubMed, and relevant congress abstracts. Studies were evaluated for eligibility using population, intervention, comparison, outcome, study design criteria and time period (Dec 2021-Nov 2022) (Table 1). Dual-independent screening was used at the title, abstract and full-text levels with third reviewer consensus; data were extracted by a single reviewer with validation by a second reviewer prior to a quality rating assessment.Table 1.Population-Intervention-Comparators-Outcomes-Study Design Criteria Results The SLR identified 28 eligible studies (Figure 1) representing 74,386 subjects that received NMV-r. The majority of studies reported on use in the United States (n=13) and patient vaccination status (n=25). Of the 16 studies that reported variant or sub-lineage data, all included patients treated during the Omicron period. Despite differences in baseline patient characteristics, treatment with NMV-r was consistently associated with a reduction in relative risk for hospitalization alone (n=5) or hospitalization and mortality (n=20). Studies that measured 30-day all-cause hospitalization (n=3) reported odds ratios (ORs) ranging from 0.43 to 0.54 (NMV-r vs. no NMV-r). Three studies measured 28-day all-cause mortality and reported ORs ranging from 0.05 to 0.23 (NMV-r vs. no NMV-r).Figure 1.Preferred Reporting Items for Systematic Reviews and Meta-Analyses Flow Diagram Conclusion Real-world studies show that NMV-r provides effective protection against hospitalization and death during the Omicron era among high-risk individuals. Outcomes following use of NMV-r in the real-world should be continually monitored as new studies are published and as the natural history of COVID-19 and treatment landscape continue to evolve. Disclosures Ashley S. Cha-Silva, PharmD, MS, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Meghan B. Gavaghan, MPH, Pfizer: Advisor/Consultant Jennifer L. Nguyen, ScD, MPH, MHCI, pfizer: employee Ronika Alexander-Parrish, RN, MAEd, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Jingyan Yang, MHS, DrPH, Pfizer Inc.: Stocks/Bonds Jaymin Patel, PharmD, Pfizer: Advisor/Consultant Denise A. Garner, PharmD, Pfizer: Advisor/Consultant Richard Stanford, PharmD, MS, Pfizer: Advisor/Consultant Genevieve Meier, PharmD, MSc, PhD, Pfizer: Advisor/Consultant

Carriage of Streptococcus pneumoniae (pneumococcus) in the upper respiratory tract is considered a prerequisite to invasive pneumococcal disease. During the first year of the COVID-19 pandemic, markedly lower rates of invasive pneumococcal disease were reported worldwide.

Abstract Background Important questions remain about the role of older adults in driving transmission of pneumococcus in the community. This is a critical question for understanding the potential indirect effects of using pneumococcal conjugate vaccines (PCVs) in older adults. For non-institutionalized individuals, the most likely source of adult-to-adult transmission is in the household. The goal of this study was to characterize the dynamics and risk factors for acquisition of pneumococcus in older adults. Methods We designed a longitudinal study to sample adults > 60 years of age living in the same household (New Haven, CT), and without younger contacts residing in the household. Saliva samples and questionnaires regarding social behaviors and health status were obtained every 2 weeks for a period of 10 weeks. DNA extracted from culture-enriched saliva was tested using qPCR for pneumococcus genes piaB and lytA. Results Across the two study seasons (November 2020-August 2021, November 2021-September 2022), 184 individuals from 93 households were sampled and completed all 6 visits. Overall, 31/184 (16.8%) individuals were colonized on at least one time point based on qPCR detection of piaB. Two individuals were colonized at 6/6 time points, and two others were colonized at 5/6 time points during the 10-week sampling period. In 7/93 (7.5%) households, both members were colonized, though not necessarily at the same time point. Pneumococcal colonization was substantially higher among individuals who had contact with children < 18 years as compared to those with no recent contact with children (9.4% vs 2.3%). Participants who reported recent contact with < 5 year olds and 5-9 year olds had particularly elevated prevalence (14.3%; 13.0%, respectively). Conclusion Pneumococcal acquisition related to adult-to-adult transmission is low. Contact with pre-school and young school-aged children was the most important factor that influenced acquisition rates of pneumococcus among older adult households. Disclosures Anne L. Wyllie, PhD, Co-Diagnostics: Board Member|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support Ronika Alexander-Parrish, RN, MAEd, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Adriano Arguedas, Medical director, Pfizer: Emplyee|Pfizer: Stocks/Bonds Bradford D. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Daniel M. Weinberger, PhD, GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support

IMPORTANCE Following routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in children in 2010, invasive pneumococcal disease rates have decreased substantially in children and adults. In 2014, the Advisory Committee for Immunization Practices recommended routine use of PCV13 among adults aged 65 years or older; previously only 23-valent pneumococcal polysaccharide vaccine (PPV23) was recommended. OBJECTIVE To estimate the association between the incidence of hospitalized all-cause pneumonia and lower respiratory tract infections (LRTI) and PCV13 vaccination among older adults at Kaiser Permanente Northern California (KPNC). DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included adults at KPNC aged 65 years or older between July 1, 2015, and June 30, 2018, born after 1936 with no known history of PPV23 or PCV13 receipt before age 65. The study took place at an integrated health care system with an annual membership more than 4 million individuals, approximately 15% of whom are 65 years or older and broadly representative of the region. Data analysis took place from July 2018 to December 2021, and data collection took place from November 2016 to June 2018. EXPOSURES PCV13 vaccination status was ascertained from the electronic medical record (EMR). Individuals were considered vaccinated 14 days following immunization. MAIN OUTCOMES AND MEASURES First hospitalized all-cause pneumonia was identified in the EMR using primary/secondary discharge diagnosis International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. First hospitalized LRTI was identified using pneumonia codes and acute bronchitis codes. Relative risk (RR) of first pneumonia or LRTI hospitalization of individuals who were PCV13 vaccinated vs PCV13 unvaccinated was estimated using Poisson regressions adjusted for sex, race, ethnicity, age, influenza vaccine receipt, PPV23 receipt since age 65, pneumonia risk factors, health care use, and season. Vaccine effectiveness (VE) was estimated as (1-RR) x 100%. RESULTS Of 192 061 adults, 107 957 (56%) were female and 139 024 (72%) were White individuals. PCV13 coverage increased from 0 in 2014 to 135 608 (76.9%) by 2018. There were 3488 individuals with 3766 pneumonia hospitalizations and 3846 individuals with 4173 LRTI hospitalizations. PCV13 was associated with an adjusted VE of 10.0% (95% CI, 2.4-17.0; P = .01) against hospitalized pneumonia and 9.4% (95% CI, 2.1-16.1; P = .01) against hospitalized LRTI. CONCLUSIONS AND RELEVANCE In the context of a robust pediatric PCV13 immunization program, PCV13 vaccination of adults aged 65 years or older was associated with significant reductions in hospitalizations for all-cause pneumonia and LRTI. Vaccinating older adults with PCVs may provide broader public health benefit against pneumonia hospitalizations.

Objectives To determine the incidence, aetiology and pneumococcal serotype distribution of community-acquired pneumonia (CAP) in Brazilian adults during a 2-year period. Design Prospective population-based surveillance study. Setting Patients from two emergency hospitals in Brazil were consecutively included in this study. Participants A total of 111 adults aged 50 years and older with radiographically-confirmed CAP requiring an emergency department visit were prospectively enrolled between January 2018 and January 2020. Main outcome measures Incidence rates of CAP were calculated according to age and pathogen. Pathogens were identified by conventional microbiological methods. Additionally, a novel, Luminex-based serotype specific urinary antigen detection assay was used to detect serotypes included in pneumococcal vaccines. Results Mean age of participants was 64 years and 31% were aged ≥70 years. Aetiology was established in 61 (57%) patients; among identified cases, the most common pathogens were Streptococcus pneumoniae (42/61, 69%) and influenza (4/61, 7%). Among serotypes identified from the 42 cases of pneumococcal CAP, estimated coverage ranged by pneumococcal vaccine formulations from 47.6% (13-valent), 59.5% (20-valent, licenced in the USA only) and 71.4% (23-valent). In patients with CAP, 20-valent pneumococcal vaccine serotypes were identified 2.5 times more frequently than 10-valent pneumococcal vaccine serotypes (22.5% vs 9.0%). The incidence rate for CAP in adults aged ≥50 years was 20.1 per 10 000 person-years. In general, the incidence of CAP increased consistently with age, reaching 54.4 (95% CI 36.8 to −76.6) per 10 000 in adults 80 years or older. Conclusions We observed a high burden of pneumococcal CAP among adults in Brazil. Despite the routine immunisation of children and high-risk adults against pneumococcal disease in the Brazilian national vaccination programme, a persistent burden of pneumococcal CAP caused by vaccine serotypes remains in this population.

ABSTRACT Background Infections with respiratory viruses (e.g., influenza, RSV) can increase the risk of severe pneumococcal infections. Likewise, pneumococcal co-infection is associated with poorer outcomes in viral respiratory infection. However, there are limited data describing the frequency of pneumococcus and SARS-CoV-2 co-infection and the role of co-infection in influencing COVID-19 severity. Methods The study included patients admitted to Yale-New Haven Hospital who were symptomatic for respiratory infection and tested positive for SARS-CoV-2 during March-August 2020. Patients were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and serotype-specific urine antigen detection (UAD) assays (to identify presumed lower respiratory tract pneumococcal disease). Results Among 148 subjects, the median age was 65 years; 54.7% were male; 50.7% had an ICU stay; 64.9% received antibiotics; 14.9% died while admitted. Pneumococcal carriage was detected in 3/96 (3.1%) individuals tested by saliva RT-qPCR. Additionally, pneumococcus was detected in 14/127 (11.0%) individuals tested by UAD, and more commonly in severe than moderate COVID-19 (OR: 2.20; 95% CI: [0.72, 7.48]); however, the numbers were small with a high degree of uncertainty. None of the UAD-positive individuals died. Conclusions Pneumococcal LRTI, as detected by positive UAD, occurred in patients hospitalized with COVID-19. Moreover, pneumococcal LRTI was more common in those with more serious COVID-19 outcomes. Future studies should assess how pneumococcus and SARS-CoV-2 interact to influence COVID-19 severity in hospitalized patients. One Sentence Summary Pneumococcal lower respiratory tract infection, as detected by positive UAD, occurred in patients hospitalized with COVID-19 at rates similar to those reported prepandemic.

Streptococcus pneumoniae is a major cause of community-acquired pneumonia, bacteremia, and meningitis in older adults worldwide. Two pneumococcal vaccines containing S. pneumoniae capsular polysaccharides are in current use: the polysaccharide vaccine PPSV23 and the glycoconjugate vaccine PCV13. In clinical trials, both vaccines elicit similar opsonophagocytic killing activity. In contrast to polysaccharide vaccines, conjugate vaccines have shown consistent efficacy against nasopharyngeal carriage and noninvasive pneumonia overall and for some prevalent individual serotypes. Given these different clinical profiles, it is crucial to understand the differential immunological responses induced by these two vaccines. Here, we used a high-throughput systems serology approach to profile the biophysical and functional features of serum antibodies induced by PCV13 and PPSV23 at 1 month and 1 year. In comparison with PPSV23, PCV13 induced higher titers across antibody isotypes; more durable antibody responses across immunoglobulin G (IgG), IgA, and IgM isotypes; and increased antigenic breadth. Although titers measured in opsonophagocytic activity (OPA) assays were similar between the two groups, confirming what was observed in clinical studies, serum samples from PCV13 vaccinees could induce additional non-OPA antibody-dependent functions, including monocyte phagocytosis and natural killer cell activation. In a multivariate modeling approach, distinct humoral profiles were demonstrated in each arm. Together, these results demonstrate that the glycoconjugate PCV13 vaccine induces an antigenically broader, more durable, polyfunctional antibody response. These findings may help explain the increased protection against S. pneumoniae colonization and noninvasive pneumonia and the longer duration of protection against invasive pneumococcal disease, mediated by PCV13.

BACKGROUND:Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. METHODS:This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). RESULTS:Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. CONCLUSIONS:The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine.

Abstract Background Despite the widespread use of pneumococcal conjugate vaccines, particularly in children, an important burden of pneumococcal disease remains in older adults. The acquisition and transmission rates of pneumococcus between older adults have not been well characterized. Methods Between October 2020-June 2021, couples living in the Greater New Haven Area were enrolled if both individuals were over the age of 60 years and did not have any individuals under the age of 60 years living in the household. Saliva samples and questionnaires regarding social patterns and medical history were obtained every 2 weeks for a period of 10 weeks. Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive for pneumococcal carriage when qPCR Ct-values for piaB +/- lytA were less than 40. Results To date, we have collected 495 saliva samples from 95 individuals (48 households). Of 495 saliva samples, 31 (5.9%) have tested positive for pneumococcus by either piaB only (n=9) or both lytA and piaB (n=22). Of 95 individuals, 16 (16.8%) (representing 13, or 27.1% households) have tested positive at least once. Six of the 16 (37.5%) carriers tested positive at multiple timepoints, though none were colonized at all 6 time points over the course of the 10 weeks of study enrolment. For 3 of the 48 (6.3%) households, both members of the couple were identified as carriers, though not necessarily at the same sampling moment. Conclusion The preliminary findings of this longitudinal transmission model demonstrate evidence of pneumococcal acquisition among older adults measured by molecular tools. These transmission patterns and high rates of pneumococcal carriage in adults were observed during a period when the COVID-19 pandemic led to numerous preventative public health measures that may have reduced pneumococcal transmission (e.g., social distancing, mask wearing, bans on mass gatherings, restaurant closures, travel restrictions). Disclosures Anne Wyllie, PhD, Global Diagnostic Systems (Consultant)Pfizer (Advisor or Review Panel member, Research Grant or Support)PPS Health (Consultant)Tempus Labs, Inc (Research Grant or Support) Ronika Alexander-Parrish, RN, MAEd, Pfizer (Employee, Shareholder) Adriano Arguedas, MD, Pfizer (Employee) Bradford D. Gessner, MD, MPH, Pfizer Inc. (Employee) Daniel Weinberger, PhD, Affinivax (Consultant)Merck (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)

Introduction: Comprehensive vaccination coverage among homeless children in the United States (US) is largely unknown although a few studies suggest low coverage with single vaccinations. This study compared vaccination coverage with a combined 7-vaccines series among homeless children in the District of Columbia (DC) to coverage among other US children. Materials and methods: A cross-sectional survey of homeless children in DC was conducted from 2018 to 2019. Recruitment occurred at housing shelters, social services centers, and a diaper dispensary, and through limited chain referral. English-speaking parents of a child aged 19 to 35 months who spent the majority of the last 30 nights homeless were recruited. Participants consented for their child's healthcare providers to submit vaccination records. The vaccination coverage estimate of this sample was compared with estimates of three populations in the 2018 National Immunization Survey (NIS): children in DC (NIS DC), children in the US (NIS US), and children in the US below the federal poverty level (NIS poor). Results: Most of the 135 children had experienced at least two lifetime episodes (63.7%) and 12 months (57%) of homelessness. The estimated percent up to date was 52.6% (95% CI: 43.8%, 61.3%). This estimate was 20.4 (95% CI: 11.9, 28.8, p < .0001), 20 (95% CI: 11.5, 28.4, p < .0001), and 11.5 (95% CI: 3.1, 20, p < .01) percentage points lower than estimates for the NIS DC, NIS US and NIS poor populations, respectively. After adjusting for child's age and race/ethnicity, vaccination coverage of the NIS DC sample was below that of NIS US (p < .01) and NIS poor samples (p < .05). Conclusion: Children experiencing homelessness may be at risk of under-vaccination, even when compared to a general population of children in poverty. Awareness of this heightened risk may allow for more precise targeting of vaccination delivery support specifically to children experiencing homelessness. (c) 2021 Elsevier Ltd. All rights reserved.

Objectives To examine parental beliefs and logistical challenges to early childhood vaccination completion as well as opportunities to support improved vaccine uptake among families experiencing homelessness. Study design A cross-sectional survey was conducted between February 2018 and October 2019 with parents of children ages 19-35 months old experiencing homelessness. Participants were recruited from 10 locations that serve families experiencing homelessness in Washington, DC and by referral from other participants. Vaccination records were obtained from health care providers to determine the child's up-to-date (UTD) status with a combined 7-vaccine series. Results Of 135 children of participants, only 69 (51.1%) were UTD. Most participants had at least 1 concern about childhood vaccines and at least 1 logistical barrier to completing vaccination (57% and 85.9%, respectively). The most frequent barriers were getting a convenient appointment time (46.3%), remembering appointments (44.8%), and commuting to appointments (44.4%). Although only 53.3% of the participants' children attended a licensed daycare center and only 43.7% received benefits from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), use of either of these programs that routinely assess vaccination status was associated with over 3 times higher adjusted odds of being UTD (aOR 3.4, 95% CI 1.6-7.3, and aOR 3.1, 95% CI 1.4-6.5, respectively). Conclusions Logistical barriers to accessing primary care services are common among children experiencing homelessness, underscoring the importance of health care providers offering vaccines at every opportunity. Government-regulated programs are useful for promoting vaccination, and enrollment should be encouraged because many children experiencing homelessness may not access them.

Abstract Background Streptococcus pneumoniae (pneumococcus) is a common colonizer of the upper respiratory tract and can progress to cause invasive and mucosal disease. Additionally, infection with pneumococcus can complicate respiratory viral infections (influenza, respiratory syncytial virus, etc.) by exacerbating the initial disease. Limited data exist describing the potential relationship of SARS-CoV-2 infection with pneumococcus and the role of co-infection in influencing COVID-19 severity. Methods Inpatients and healthcare workers testing positive for SARS-CoV-2 during March-August 2020 were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and for inpatients only, serotype-specific urine antigen detection (UAD) assays (to identify pneumococcal pneumonia). A multinomial multivariate regression model was used to examine the relationship between pneumococcal detection and COVID-19 severity. Results Among the 126 subjects who tested positive for SARS-CoV-2, the median age was 62 years; 54.9% of subjects were male; 88.89% were inpatients; 23.5% had an ICU stay; and 13.5% died. Pneumococcus was detected in 17 subjects (13.5%) by any method, including 5 subjects (4.0%) by RT-qPCR and 12 subjects (13.6%) by UAD. Little to no bacterial growth was observed on 21/235 culture plates. Detection by UAD was associated with both moderate and severe COVID-19 disease while RT-qPCR detection in saliva was not associated with severity. None of the 12 individuals who were UAD-positive died. Conclusion Pneumococcal pneumonia (as determined by UAD) continues to occur during the ongoing pandemic and may be associated with more serious COVID-19 outcomes. Detection of pneumococcal carriage may be masked by high levels of antibiotic use. Future studies should better characterize the relationship between pneumococcus and SARS-CoV-2 across all disease severity levels. Disclosures Akiko Iwasaki, PhD, 4Bio (Consultant, Advisor or Review Panel member)Adaptive Biotechnologies (Consultant, Advisor or Review Panel member)Blavatnik (Grant/Research Support)HHMI (Grant/Research Support)Mathers (Grant/Research Support)NIH (Grant/Research Support)Spring Discovery (Grant/Research Support)Spring Discovery (Consultant, Advisor or Review Panel member)Vedanta InProTher (Consultant, Advisor or Review Panel member)Yale School of Medicine (Grant/Research Support) Nathan D. Grubaugh, PhD, Tempus Labs (Consultant) Ronika Alexander-Parrish, RN, MAEd, Pfizer (Employee, Shareholder) Adriano Arguedas, MD, Pfizer (Employee) Bradford D. Gessner, MD, MPH, Pfizer Inc. (Employee) Daniel Weinberger, PhD, Affinivax (Consultant)Merck (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support) Anne Wyllie, PhD, Global Diagnostic Systems (Consultant)Pfizer (Advisor or Review Panel member, Research Grant or Support)PPS Health (Consultant)Tempus Labs, Inc (Research Grant or Support)

Abstract Background Routine use of 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants since early 2010 and for adults ≥65 years since 2014 when KPNC began routine use of PCV13 in adults. PCV13 vaccine effectiveness (VE) against vaccine-type invasive pneumococcal disease (IPD) has been demonstrated; however, recent surveillance data have been interpreted as showing limited population-level impact of PCV13 on serotype 3 IPD. We estimated PCV13 VE against IPD due to vaccine serotypes at Kaiser Permanente Northern California (KPNC). Methods The study period spanned September 2014 through September 2018. The cohort included KPNC members who were aged ≥65 years with no record of pneumococcal polysaccharide vaccine (PPV23) receipt before age 65 years. We compared IPD cases with KPNC members who were the same age on the date of the positive pneumococcal culture using conditional logistic regression, conditioned on age and date, and controlled for sex, race, KPNC service area and membership history, prior season influenza vaccine receipt, PPV23 receipt after age 65 years, risk factors for IPD, and healthcare utilization. Results From September 2014 to September 2018, PCV13 vaccine coverage among persons ≥65 years old increased from < 1% to 77%. During the same period, there was a total of 245 IPD cases. For a variety of reasons, we did not have serotype results for 57 (23%) IPD cases, which were excluded from the analysis. There were 61 (25%) PCV13-type IPD cases included in the analysis, of which 33 (14%) were serotype 3. PCV13 VE against PCV13-type serotypes was 68.0% (95% CI: 37.7%, 83.6%; P-value < 0.01), and 53.4% (95% CI: −10.0%, 80.3%; P = 0.08) against serotype 3. Conclusion During the first 4 years of PCV13 vaccination implementation in adults ≥65 years of age at KPNC, PCV13 provided significant protection against PCV13-type IPD. Further surveillance will allow for more precise estimation of PCV13 VE on overall and serotype 3 IPD over time. Disclosures All authors: No reported disclosures.

Abstract Background Native Americans experience a high burden of community-acquired pneumonia (CAP). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was introduced for adults ≥65yrs in 2014. Data on CAP etiology can guide prevention and treatment. Methods We enrolled adults hospitalized with CAP and age-group-matched non-hospitalized controls on Navajo and White Mountain Apache tribal lands. Nasopharyngeal/oropharyngeal (NP/OP) swabs from cases and controls were tested by multiplex PCR for respiratory pathogens. Urine from cases and controls was tested for pneumococcus (Sp) by conventional (BinaxNOW) and serotype-specific urine antigen detection (UAD) for 24 serotypes (PCV13 types plus 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, 33F). Blood culture and chest radiographs (CXRs) were obtained from cases at the provider’s discretion. Radiographic pneumonia was determined by clinical interpretation of CXRs. Results From March 2016 to March 2018, we enrolled 580 CAP cases with CXR confirmation and 411 controls. Positive blood culture was identified in 42/483 (9%), of which 29 (69%) were Sp. Sp was detected in 164/572 (29%) cases (table). Of 125 cases with serotype information available, serotypes 3 (n = 35; 28%) 8 (n = 19; 15%) and 20 (n = 15; 12%) were the most common. Among 53 Sp cases aged ≥65 years, 26 (49%) were PCV13-type. Compared with blood culture, UAD was 100% sensitive and 100% concordant (n = 24). Viruses were detected by NP/OP PCR in 43% of CAP cases and 18% of controls. Influenza A, parainfluenza type 3, rhinovirus, and RSV were statistically significantly associated with case status. Among 263 cases in whom all diagnostic tests were collected, 63% had a pathogen detected: bacteria alone in 19%, viruses alone in 23%, and both bacterial and viral infection in 22%. Bacterial causes outnumbered viral causes when adjusting for virus detection in the control population. Conclusion Pneumococci were the most common etiology identified among Native American adults with CAP. UAD improved detection of pneumococcal CAP. Respiratory viruses also contributed substantially to CAP burden. Broader prevention strategies, including new vaccines, are required to prevent viral pneumonia and pneumococcal pneumonia caused by serotypes not contained in currently-available vaccines. Disclosures All authors: No reported disclosures.