ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway.

The ATR-CHK1 DNA damage response pathway becomes activated by the exposure of RPA-coated single-stranded DNA (ssDNA) that forms as an intermediate during DNA damage and repair, and as a part of the replication stress response. Here, we identify ZNF827 as a component of the ATR-CHK1 kinase pathway. We demonstrate that ZNF827 is a ssDNA binding protein that associates with RPA through concurrent binding to ssDNA intermediates. These interactions are dependent on two clusters of C2H2 zinc finger motifs within ZNF827. We find that ZNF827 accumulates at stalled forks and DNA damage sites, where it activates ATR and promotes the engagement of homologous recombination-mediated DNA repair. Additionally, we demonstrate that ZNF827 depletion inhibits replication initiation and sensitizes cancer cells to the topoisomerase inhibitor topotecan, revealing ZNF827 as a therapeutic target within the DNA damage response pathway.

The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation.

The Eyes Absent proteins (EYA1-4) are a biochemically unique group of tyrosine phosphatases known to be tumour-promoting across a range of cancer types. To date, the targets of EYA phosphatase activity remain largely uncharacterised. Here, we identify Polo-like kinase 1 (PLK1) as an interactor and phosphatase substrate of EYA4 and EYA1, with pY445 on PLK1 being the primary target site. Dephosphorylation of pY445 in the G2 phase of the cell cycle is required for centrosome maturation, PLK1 localization to centrosomes, and polo-box domain (PBD) dependent interactions between PLK1 and PLK1-activation complexes. Molecular dynamics simulations support the rationale that pY445 confers a structural impairment to PBD-substrate interactions that is relieved by EYA-mediated dephosphorylation. Depletion of EYA4 or EYA1, or chemical inhibition of EYA phosphatase activity, dramatically reduces PLK1 activation, causing mitotic defects and cell death. Overall, we have characterized a phosphotyrosine signalling network governing PLK1 and mitosis.

Distinct modes of telomere synthesis and extension contribute to Alternative Lengthening of Telomeres.

Alternative lengthening of telomeres (ALT) is a homology-directed repair mechanism that becomes activated in a subset of cancers to maintain telomere length. One of the defining features of ALT cells is the prevalence of extrachromosomal telomeric repeat (ECTR) DNA. Here, we identify that ALT cells engage in two modes of telomere synthesis. Non-productive telomere synthesis occurs during the G2 phase of the cell cycle and is characterized by newly synthesized internal telomeric regions that are not retained in the subsequent G1, coinciding with an induction of ECTR DNA. Productive telomere synthesis occurs specifically during the transition from G2 to mitosis and is defined as the extension of the telomere termini. While many proteins associated with break-induced telomere synthesis function in both non-productive and productive telomere synthesis, POLH specifically promotes productive telomere lengthening and suppresses non-productive telomere synthesis. These findings delineate the mechanism and cell cycle regulation of ALT-mediated telomere synthesis and extension.

Deconstructing heterogeneity of replicative senescence in human mesenchymal stem cells at single cell resolution.

Following prolonged cell division, mesenchymal stem cells enter replicative senescence, a state of permanent cell cycle arrest that constrains the use of this cell type in regenerative medicine applications and that in vivo substantially contributes to organismal ageing. Multiple cellular processes such as telomere dysfunction, DNA damage and oncogene activation are implicated in promoting replicative senescence, but whether mesenchymal stem cells enter different pre-senescent and senescent states has remained unclear. To address this knowledge gap, we subjected serially passaged human ESC-derived mesenchymal stem cells (esMSCs) to single cell profiling and single cell RNA-sequencing during their progressive entry into replicative senescence. We found that esMSC transitioned through newly identified pre-senescent cell states before entering into three different senescent cell states. By deconstructing this heterogeneity and temporally ordering these pre-senescent and senescent esMSC subpopulations into developmental trajectories, we identified markers and predicted drivers of these cell states. Regulatory networks that capture connections between genes at each timepoint demonstrated a loss of connectivity, and specific genes altered their gene expression distributions as cells entered senescence. Collectively, this data reconciles previous observations that identified different senescence programs within an individual cell type and should enable the design of novel senotherapeutic regimes that can overcome in vitro MSC expansion constraints or that can perhaps slow organismal ageing.

Epidemiology of RSV Bronchiolitis Among Young Children in Central New York Before and After the Onset of the COVID-19 Pandemic.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalizations among infants in the United States. Unpredictability in RSV seasonality has occurred following the onset of the coronavirus disease 2019 (COVID-19) pandemic. Local surveillance networks can enhance the ability to appropriately time prophylaxis when exposure risk is highest. METHODS: A retrospective, cohort study was conducted to describe the epidemiologic patterns of RSV disease among outpatient, emergency department and inpatient encounters in children <5 years in Central New York before and after the onset of the COVID-19 pandemic. Local data were collected from October 2015 to January 2023 and compared to state-level data. Linear regression models were used to identify clinical and sociodemographic differences before and after the pandemic. RESULTS: Local variation in RSV seasonality was noted prior to the COVID-19 pandemic, however highly atypical circulation patterns appeared in the post-COVID-19 era. Since March 2020, patterns for local and state-defined RSV seasons have remained atypical (local season onset in 2021: week 27 and 2022: week 27; state season onset in 2021: week 31 and 2022: week 38). After adjusting for increases in testing, RSV bronchiolitis cases were not significantly different during pre- and post-pandemic eras. In comparison to the 2021 bronchiolitis season, the 2022 season had a higher proportion of RSV cases despite decreased testing. CONCLUSIONS: Temporal patterns for RSV have shifted during the COVID-19 pandemic. Local surveillance networks may be advantageous in trending community-level RSV activity to optimize prophylaxis administration. Changes in RSV testing patterns occurred throughout the study period and should be accounted for when describing infant and childhood RSV disease.

Optimal site of care for administration of extended half-life respiratory syncytial virus (RSV) antibodies to infants in the United States (US).

INTRODUCTION: New extended half-life antibodies for the single-dose prevention of medically attended (MA) respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) have been developed for administration to all infants before or during their first RSV season. For infants born during the season, administration as soon as feasible after birth would provide optimal protection and minimize access disparities. The objective of this study was to assess the time from birth hospitalization discharge to the first outpatient visit (FOV) among US infants in order to determine optimal site of administration for the extended half-life antibody. MATERIAL AND METHODS: This retrospective, observational, time-to-event analysis uses the Merative™ MarketScan® Commercial and Multi-State Medicaid Databases. Time to FOV is reported separately for the COVID-19 and recent pre-COVID-19 eras and for commercially insured and Medicaid infants. RESULTS: Overall, 73.8 % of Medicaid infants had an FOV within 5 days as compared to 84.7 % of commercially insured infants. Estimates were higher during the COVID-19 era. Urban commercially insured infants had much higher FOV completion than their counterparts. Among Medicaid infants, urban Black and rural White infants were least likely to complete their FOV within 5 days of birth hospitalization discharge. DISCUSSION AND CONCLUSION: FOV within 5 days after birth hospitalization discharge for Medicaid infants is substantially lower than that of commercially insured infants. Approximately 1 in 4 Medicaid infants and 1 in 8 infants with commercial insurance did not have an outpatient visit within 5 days of birth hospitalization discharge. For US infants born during the RSV season, administration of extended half-life RSV antibodies in the newborn nursery prior to discharge would ensure optimal uptake and minimize access disparities.

Quality of life burden on United States infants and caregivers due to lower respiratory tract infection and adjusting for selective testing: Pilot prospective observational study.

Background and Aims: Policymakers need data about the burden of respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI) among infants. This study estimates quality of life (QoL) for otherwise healthy term US infants with RSV-LRTI and their caregivers, previously limited to premature and hospitalized infants, and corrects for selective testing. Methods: The study enrolled infants <1 year with a clinically diagnosed LRTI encounter between January and May 2021. Using an established 0-100 scale, the 36 infants' and caregivers' QoL at enrollment and quality-adjusted life year losses per 1000 LRTI episodes (quality-adjusted life years [QALYs]/1000) were validated and analyzed. Regression analyses examined predictors of RSV-testing and RSV-positivity, creating modeled positives. Results: Mean QoL at enrollment in outpatient (n = 11) LRTI-tested infants (66.4) was lower than that in not-tested LRTI infants (79.6, p = 0.096). For outpatient LRTI infants (n = 23), median QALYs/1000 losses were 9.8 and 0.25 for their caregivers. RSV-positive outpatient LRTI infants (n = 6) had significantly milder QALYs/1000 losses (7.0) than other LRTI-tested infants (n = 5)(21.8, p = 0.030). Visits earlier in the year were more likely to be RSV-positive than later visits (p = 0.023). Modeled RSV-positivity (51.9%) was lower than the observed rate (55.0%). Infants' and caregivers' QALYs/1000 loss were positively correlated (rho = 0.34, p = 0.046), indicating that infants perceived as sicker imposed greater burdens on caregivers. Conclusions: The overall median QALYs/1000 losses for LRTI (9.0) and RSV-LRTI (5.6) in US infants are substantial, with additional losses for their caregivers (0.25 and 0.20, respectively). These losses extend equally to outpatient episodes. This study is the first reporting QALY losses for infants with LRTI born at term or presenting in nonhospitalized settings, and their caregivers.

Public health impact and cost-effectiveness of implementing a 'pre-vaccination screening' strategy with the dengue vaccine in Puerto Rico.

BACKGROUND: The World Health Organization (WHO) recommended 'pre-vaccination screening' as its preferred implementation strategy when using the licensed dengue vaccine (CYD-TDV; Dengvaxia, Sanofi), so that only individuals with previous dengue infection are vaccinated. The US Centers for Disease Control and Prevention (CDC) recommended use of CYD-TDV to prevent dengue in children with previous laboratory-confirmed dengue infection in regions where dengue is endemic. Here, we evaluate the public health impact and cost-effectiveness of a 'pre-vaccination screening' strategy in Puerto Rico. METHODS: The current analysis builds upon a previously published transmission model used to assess the benefits/risks associated with dengue vaccination. For 'pre-vaccination screening', three alternative testing methods were assessed: one using an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) dengue serotest, another with dengue serotesting using a rapid diagnostic test (RDT), and one using both sequentially (as recommended in Puerto Rico). The time horizon considered was 10 years. RESULTS: In Puerto Rico, the disability-adjusted life years (DALYs) averted for 'pre-vaccination screening' with an ELISA-based program, RDT-based program, and both sequentially would be a median 1,192 (95% CI: 716-2,232), 2,812 (95% CI: 1,579-5,019), and 1,017 (95% CI: 561-1,738), respectively. These benefits would arise from the reduction in cases: median 24,961 (95% CI: 17,480-36,782), 58,273 (95% CI: 40,729-84,796), 20,775 (95% CI: 14,637-30,374) fewer cases, respectively. The cost per DALY averted from a payer perspective would be US$12,518 (95 %CI: US$4,749-26,922), US$10,047 (95% CI: US$3,350-23,852), and US$12,334 (95% CI: US$4,965-26,444), respectively. All three strategies would be cost saving from a societal perspective. CONCLUSIONS: Our study supports the WHO and CDC 'pre-vaccination screening' guidance for CYD-TDV implementation. In Puerto Rico, regardless of the testing strategy and even with a relatively low rate of testing, it would be cost-effective from a payer perspective and cost saving from a societal perspective.

Inequalities in Health Impact of Alternative Reimbursement Pathways for Nirsevimab in the United States.

The target populations and financing mechanisms for a new health technology may affect health inequalities in access and impact. We projected the distributional consequences of introducing nirsevimab for prevention of respiratory syncytial virus in a US birth cohort of infants through alternative reimbursement pathway scenarios. Using the RSV immunization impact model, we estimated that a vaccine-like reimbursement pathway would cover 32% more infants than a pharmaceutical pathway. The vaccine pathway would avert 30% more hospitalizations and 39% more emergency room visits overall, and 44% and 44%, respectively, in publicly insured infants. The vaccine pathway would benefit infants from poorer households.

Medically Attended Illness due to Respiratory Syncytial Virus Infection Among Infants Born in the United States Between 2016 and 2020.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization in the United States. Preterm infants and those with select comorbidities are at highest risk of RSV-related complications. However, morbidity due to RSV infection is not confined to high-risk infants. We estimated the burden of medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) among infants in the United States. METHODS: We analyzed commercial (MarketScan Commercial [MSC], Optum Clinformatics [OC]), and Medicaid (MarketScan Medicaid [MSM]) insurance claims data for infants born between April 2016 and February 2020. Using both specific and sensitive definitions of MA RSV LRTI, we estimated the burden of MA RSV LRTI during infants' first RSV season, stratified by gestational age, comorbidity status, and highest level of medical care associated with the MA RSV LRTI diagnosis. RESULTS: According to the specific definition 75.0% (MSC), 78.6% (MSM), and 79.6% (OC) of MA RSV LRTI events during infants' first RSV season occurred among term infants without known comorbidities. CONCLUSIONS: Term infants without known comorbidities account for up to 80% of the MA RSV LRTI burden in the United States during infants' first RSV season. Future prevention efforts should consider all infants.

Respiratory Syncytial Virus During the COVID-19 Pandemic Compared to Historic Levels: A Retrospective Cohort Study of a Health System.

BACKGROUND: Surveillance in 2020-2021 showed that seasonal respiratory illnesses were below levels seen during prior seasons, with the exception of interseasonal respiratory syncytial virus (RSV). METHODS: Electronic health record data of infants aged <1 year visiting the Duke University Health System from 4 October 2015 to 28 March 2020 (pre-COVID-19) and 29 March 2020 to 30 October 2021 (COVID-19) were assessed. International Classification of Diseases-Tenth Revision (ICD-10) codes for RSV (B97.4, J12.1, J20.5, J21.0) and bronchiolitis (RSV codes plus J21.8, J21.9) were used to detail encounters in the inpatient (IP), emergency department (ED), outpatient (OP), urgent care (UC), and telemedicine (TM) settings. RESULTS: Pre-COVID-19, 88% of RSV and 92% of bronchiolitis encounters were seen in ambulatory settings. During COVID-19, 94% and 93%, respectively, occurred in ambulatory settings. Pre-COVID-19, the highest RSV proportion was observed in December-January (up to 38% in ED), while the peaks during COVID-19 were seen in July-September (up to 41% in ED) across all settings. RSV laboratory testing among RSV encounters was low during pre-COVID-19 (IP, 51%; ED, 51%; OP, 41%; UC, 84%) and COVID-19 outside of UC (IP, 33%; ED, 47%; OP, 47%; UC, 87%). Full-term, otherwise healthy infants comprised most RSV encounters (pre-COVID-19, up to 57% in OP; COVID-19, up to 82% in TM). CONCLUSIONS: With the interruption of historical RSV epidemiologic trends and the emergence of interseasonal disease during COVID-19, continued monitoring of RSV is warranted across all settings as the changing RSV epidemiology could affect the distribution of health care resources and public health policy.

Impact of Respiratory Syncytial Virus on Child, Caregiver, and Family Quality of Life in the United States: Systematic Literature Review and Analysis.

BACKGROUND: Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection in US children, reduces quality of life (QOL) of children, their caregivers, and families. METHODS: We conducted a systematic literature review in PubMed, EconLit, and other databases in the United States of articles published since 2000, derived utility lost per RSV episode from cohort studies, and performed a systematic analysis. RESULTS: From 2262 unique citations, 35 received full-text review and 7 met the inclusion criteria (2 cohort studies, 4 modeling studies, and 1 synthesis). Pooled data from the 2 cohort studies (both containing only hospitalized premature infants) gave quality-adjusted life-year (QALY) losses per episode of 0.0173 at day 38. From the cohort study that also assessed caregivers' QOL, we calculated net QALYs lost directly attributable to RSV per nonfatal episode from onset to 60 days after onset for the child, caregiver, child-and-caregiver dyad of 0.0169 (167% over prematurity alone), 0.0031, and 0.0200, respectively. CONCLUSION: Published data on QOL of children in the United States with RSV are scarce and consider only premature hospitalized infants, whereas most RSV episodes occur in children who were born at term and were otherwise healthy. QOL studies are needed beyond hospitalized premature infants.

Mortality Among US Infants and Children Under 5 Years of Age with Respiratory Syncytial Virus and Bronchiolitis: A Systematic Literature Review.

BACKGROUND: A systematic literature review was conducted to summarize the mortality (overall and by disease severity factors) of US infants and children aged <5 years with respiratory syncytial virus (RSV) or all-cause bronchiolitis (ACB). METHODS: Comprehensive, systematic literature searches were conducted; articles were screened using prespecified eligibility criteria. A standard risk of bias tool was used to evaluate studies. Mortality was extracted as the rate per 100 000 or the case fatality ratio (CFR; proportion of deaths among RSV/ACB cases). RESULTS: Among 42 included studies, 36 evaluated inpatient deaths; 10 used nationally representative populations updated through 2013, and only 2 included late-preterm/full-term otherwise healthy infants and children. The RSV/ACB definition varied across studies (multiple International Classification of Diseases [ICD] codes; laboratory confirmation); no study reported systematic testing for RSV. No studies reported RSV mortality rates, while 3 studies provided ACB mortality rates (0.57-9.4 per 100 000). CFRs ranged from 0% to 1.7% for RSV (n = 15) and from 0% to 0.17% for ACB (n = 6); higher CFRs were reported among premature, intensive care unit-admitted, and publicly insured infants and children. CONCLUSIONS: RSV mortality reported among US infants and children is variable. Current, nationally representative estimates are needed for otherwise healthy, late-preterm to full-term infants and children.

Systematic Literature Review of Respiratory Syncytial Virus Laboratory Testing Practices and Incidence in United States Infants and Children <5 Years of Age.

BACKGROUND: Respiratory syncytial virus (RSV) can cause serious illness in those aged <5 years in the United States, but uncertainty remains around which populations receive RSV testing. We conducted a systematic literature review of RSV testing patterns in studies published from 2000 to 2021. METHODS: Studies of RSV, medically attended RSV lower respiratory tract infections (LRTIs), and bronchiolitis were identified using standard methodology. Outcomes were clinical decisions to test for RSV, testing frequency, and testing incidence proportions in inpatient (IP), emergency department (ED), outpatient (OP), and urgent care settings. RESULTS: Eighty good-/fair-quality studies, which reported data from the period 1988-2020, were identified. Twenty-seven described the clinical decision to test, which varied across and within settings. Two studies reported RSV testing frequency for multiple settings, with higher testing proportions in IP (n = 2, range: 83%-85%, 1996-2009) compared with ED (n = 1, 25%, 2006-2009) and OP (n = 2, 15%-25%, 1996-2009). Higher RSV testing incidence proportions were observed among LRTI infant populations in the ED (n = 1, 74%, 2007-2008) and OP (n = 2, 54%-69%, 1995-2008). Incidence proportions in LRTI populations were not consistently higher in the IP setting (n = 13). Across studies and time, there was heterogeneity in RSV testing patterns, which may reflect varying detection methods, populations, locations, time periods, and healthcare settings. CONCLUSIONS: Not all infants and children with LRTI are tested for RSV, highlighting underestimation of RSV burden across all settings.

A Systematic Literature Review of the Burden of Respiratory Syncytial Virus and Health Care Utilization Among United States Infants Younger Than 1 Year.

BACKGROUND: The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized. METHODS: We systematically reviewed studies of RSV and bronchiolitis published 2000-2021 (data years, 1979-2020). Outcomes included RSV hospitalization (RSVH)/bronchiolitis hospitalization rates, emergency department (ED)/outpatient (OP) visit rates, and intensive care unit (ICU) admissions or mechanical ventilation (MV) use among RSV-/bronchiolitis-hospitalized infants. Study quality was determined using standard tools. RESULTS: We identified 141 good-/fair-quality studies. Five national studies reported annual average RSVH rates (range, 11.6 per 1000 per year among infants aged 6-11 months in 2006 to 50.1 per 1000 per year among infants aged 0-2 months in 1997). Two national studies provided RSVH rates by primary diagnosis for the entire study period (range, 22.0-22.7 per 1000 in 1997-1999 and 1997-2000, respectively). No national ED/OP data were available. Among 11 nonnational studies, RSVH rates varied due to differences in time, populations (eg, prematurity), and locations. One national study reported that RSVH infants with high-risk comorbidities had 5-times more MV use compared to non-high-risk infants in 1997-2012. CONCLUSIONS: Substantial data variability was observed. Nationally representative studies are needed to elucidate RSV burden and HCU.

Respiratory Syncytial Virus Is the Leading Cause of United States Infant Hospitalizations, 2009-2019: A Study of the National (Nationwide) Inpatient Sample.

BACKGROUND: This study describes leading causes of hospitalization, including respiratory syncytial virus (RSV), in United States infants (<1 year) from 2009 through 2019. METHODS: Within the National (Nationwide) Inpatient Sample (NIS) data, hospitalizations were determined by primary diagnosis using International Classification of Diseases, Ninth or Tenth Revision codes. RSV was defined as 079.6, 466.11, 480.1, B97.4, J12.1, J20.5, or J21.0. Bronchiolitis was defined as 466.19, J21.8, or J21.9. Leading causes overall and by sociodemographic variables were identified. The Kids' Inpatient Database (KID) was used for confirmatory analyses. RESULTS: Acute bronchiolitis due to RSV (code 466.11 or J21.0) was the leading primary diagnosis, accounting for 9.6% (95% confidence interval [CI], 9.4%-9.9%) and 9.3% (95% CI, 9.0%-9.6%) of total infant hospitalizations from January 2009 through September 2015 and October 2015 through December 2019, respectively; it was the leading primary diagnosis in every year accounting for >10% of total infant hospitalizations from December through March, reaching >15% in January-February. From 2009 through 2011, acute bronchiolitis due to RSV was the leading primary diagnosis in every birth month. Acute bronchiolitis due to RSV was the leading cause among all races/ethnicities, except Asian/Pacific Islanders, and all insurance payer groups. KID analyses confirmed these results. CONCLUSIONS: Acute bronchiolitis due to RSV is the leading cause of US infant hospitalizations.

Mortality Associated With Respiratory Syncytial Virus, Bronchiolitis, and Influenza Among Infants in the United States: A Birth Cohort Study From 1999 to 2018.

BACKGROUND: Infant mortality due to respiratory syncytial virus (RSV) in the United States is not well understood. METHODS: From 1999 to 2018, RSV, bronchiolitis, and influenza deaths were described for infants <1 year using linked birth/death datasets from the National Vital Statistics System. Mortality was described overall and by infant birth and death characteristics. Bronchiolitis was included as the plausible upper limit of RSV, while influenza served as a comparator. RESULTS: Total infant deaths were 561 RSV, 1603 bronchiolitis, and 504 influenza, and rates were 6.9 (95% confidence interval [CI], 6.4-7.5), 19.8 (95% CI, 18.9-20.8), and 6.2 (95% CI, 5.7-6.8) per 1 000 000 live births, respectively. The highest RSV rates were observed among <29 weeks' gestational age infants (103.5; 95% CI, 81.8-129.1), American Indian/Alaskan Native (20.3; 95% CI, 11.6-33.0), and Medicaid-insured (7.3; 95% CI, 5.9-8.9). However, RSV mortality burden was greatest in full-term (53.7%), white (44.9%), and Medicaid-insured (61.7%) infants. Deaths outside the inpatient setting were 21% and 54% for RSV and bronchiolitis; more Medicaid- (58%) and other/unknown-insured (69%) infants with bronchiolitis died outside of the inpatient setting, compared to privately insured infants (48%) (P = .0327). CONCLUSIONS: These national estimates emphasize the importance of considering all infants across all healthcare settings when describing RSV mortality.

Cost of Respiratory Syncytial Virus Infections in US Infants: Systematic Literature Review and Analysis.

BACKGROUND: Limited data are available on the economic costs of respiratory syncytial virus (RSV) infections among infants and young children in the United States. METHODS: We performed a systematic literature review of 10 key databases to identify studies published between 1 January 2014 and 2 August 2021 that reported RSV-related costs in US children aged 0-59 months. Costs were extracted and a systematic analysis was performed. RESULTS: Seventeen studies were included. Although an RSV hospitalization (RSVH) of an extremely premature infant costs 5.6 times that of a full-term infant ($10 214), full-term infants accounted for 82% of RSVHs and 70% of RSVH costs. Medicaid-insured infants were 91% more likely than commercially insured infants to be hospitalized for RSV treatment in their first year of life. Medicaid financed 61% of infant RSVHs. Paying 32% less per hospitalization than commercial insurance, Medicaid paid 51% of infant RSVH costs. Infants' RSV treatment costs $709.6 million annually, representing $187 per overall birth and $227 per publicly funded birth. CONCLUSIONS: Public sources pay for more than half of infants' RSV medical costs, constituting the highest rate of RSVHs and the highest expenditure per birth. Full-term infants are the predominant source of infant RSVHs and costs.

Respiratory Syncytial Virus Burden and Healthcare Utilization in United States Infants <1 Year of Age: Study of Nationally Representative Databases, 2011-2019.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospitalizations in United States infants aged <1 year, but research has focused on select populations. METHODS: National (Nationwide) Inpatient Sample and National Emergency Department (ED) Sample data (2011-2019) were used to report RSV hospitalization (RSVH), bronchiolitis hospitalization (BH), and ED visit counts, percentage of total hospitalizations/visits, and rates per 1000 live births along with inpatient mortality, mechanical ventilation (MV), and total charges (2020 US dollars). RESULTS: Average annual RSVH and RSV ED visits were 56 927 (range, 43 845-66 155) and 131 999 (range, 89 809-177 680), respectively. RSVH rates remained constant over time (P = .5), whereas ED visit rates increased (P = .004). From 2011 through 2019, Medicaid infants had the highest average rates (RSVH: 22.3 [95% confidence interval {CI}, 21.5-23.1] per 1000; ED visits: 55.9 [95% CI, 52.4-59.4] per 1000) compared to infants with private or other/unknown insurance (RSVH: P < .0001; ED visits: P < .0001). From 2011 through 2019, for all races and ethnicities, Medicaid infants had higher average RSVH rates (up to 7 times) compared to infants with private or other/unknown insurance. RSVH mortality remained constant over time (P = .8), whereas MV use (2019: 13% of RSVH, P < .0001) and mean charge during hospitalization (2019: $21 513, P < .0001) increased. Bronchiolitis patterns were similar. CONCLUSIONS: This study highlights the importance of ensuring access to RSV preventive measures for all infants.