Respiratory Syncytial Virus In Adults Research Articles

Efficacy of Respiratory Syncytial Virus Vaccination to Prevent Lower Respiratory Tract Illness in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A systematic review and meta-analysis was designed in order to ascertain the effectiveness of respiratory syncytial virus (RSV) vaccination in preventing lower respiratory tract diseases (LRTD) in older adults (age ≥ 60 years). Studies reporting on randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) and the preprint repository medRxiv until 31 March 2024. A total of nine studies were eventually included, two of which were conference proceedings. Our analysis included five RCTs on five RSV vaccines (RSVpreF, RSVPreF3, Ad26.RSV.preF, MEDI7510, and mRNA-1345). The meta-analysis documented a pooled vaccine efficacy of 81.38% (95% confidence interval (95% CI) 70.94 to 88.06) for prevention of LRTD with three or more signs/symptoms during the first RSV season after the delivery of the vaccine. Follow-up data were available for RSVPreF3 (2 RSV seasons), RSVpreF (mid-term estimates of second RSV season), and mRNA-1345 (12 months after the delivery of the primer), with a pooled VE of 61.15% (95% CI 45.29 to 72.40). After the first season, the overall risk for developing RSV-related LRTD was therefore substantially increased (risk ratio (RR) 4.326, 95% CI 2.415; 7.748). However, all estimates were affected by substantial heterogeneity, as suggested by the 95% CI of I2 statistics, which could be explained by inconsistencies in the design of the parent studies, particularly when dealing with case definition. In conclusion, adult RSV vaccination was quite effective in preventing LRTD in older adults, but the overall efficacy rapidly decreased in the second season after the delivery of the vaccine. Because of the heterogenous design of the parent studies, further analyses are required before tailoring specific public health interventions.

The Changing Detection Rate of Respiratory Syncytial Virus in Adults in Western Australia between 2017 and 2023.

The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is underexplored. Using laboratory data, we described the detection rate of RSV in adults ≥16 years in Western Australia (WA) between 2017 and 2023. With the exception of 2020, RSV detections rose annually between 2017 and 2023, reaching 50.7 per 100,000 in 2023 (95% confidence interval [CI], 47.9-53.8). RSV testing expanded considerably across the study period, with the testing in 2023 more than five times the 2017 total. The detection rate was highest in adults ≥60 years between 2017 and 2019, particularly those ≥75 years. Following 2020, the detections in all age groups increased, with the highest detection rate in 2023 in those ≥75-years (199.5 per 100,000; 95% CI, 180.5-220). NPIs significantly impacted RSV seasonality; the preceding winter pattern was disrupted, resulting in an absent 2020 winter season and two major summer seasons in 2020/21 and 2021/22. The RSV season began to realign in 2022, reverting to a winter seasonal pattern in 2023 and the largest season in the study period. Ongoing surveillance will be required to understand the stability of these increases and to delineate the impact of new immunisation strategies.

Estimated Incidence of Hospitalizations and Deaths Attributable to Respiratory Syncytial Virus Infections Among Adults in Germany Between 2015 and 2019.

Respiratory syncytial virus (RSV) burden in adults is underestimated mainly due to unspecific symptoms and limited standard-of-care testing. We estimated the population-based incidence of hospitalization and mortality attributable to RSV among adults with and without risk factors in Germany. Weekly counts of hospitalizations and deaths for respiratory, cardiovascular, and cardiorespiratory diseases were obtained (Statutory Health Insurance database, 2015-2019). A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends, and viral activity while allowing for potential overdispersion. Weekly counts of RSV and influenza hospitalizations in children < 2years and adults ≥ 60years, respectively, were used as viral activity indicators. Models were stratified by age group and risk status (defined as presence of selected comorbidities). Population-based RSV-attributable hospitalization incidence rates were high among adults ≥ 60years: respiratory hospitalizations (236-363 per 100,000 person-years) and cardiorespiratory hospitalizations (584-912 per 100,000 person-years). RSV accounted for 2-3% of all cardiorespiratory hospitalizations in this age group. The increase in cardiorespiratory hospitalization risk associated with underlying risk factors was greater in 18-44year old persons (five to sixfold higher) than in ≥ 75year old persons (two to threefold higher). This is a first model-based study to comprehensively assess adult RSV burden in Germany. Estimated cardiorespiratory RSV hospitalization rates increased with age and were substantially higher in people with risk factors compared to those without risk factors. Our study indicates that RSV, like other respiratory viruses, contributes to both respiratory and cardiovascular hospitalizations. Effective prevention strategies are needed, especially among older adults ≥ 60years and among adults with underlying risk factors.

RSV-related Community COPD Exacerbations and Novel Diagnostics: A Binational Prospective Cohort Study.

Respiratory syncytial virus (RSV) is a common global respiratory virus increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults with acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions. This prospective study aimed to establish the frequency of outpatient-managed RSV-related exacerbations of COPD in two well-characterized patient cohorts using a combination of diagnostic methods. Participants were recruited at specialist clinics in London, UK and Groningen, NL from 2017 and observed for three consecutive RSV seasons, during exacerbations and at least twice yearly. RSV infections were detected by reverse transcription-polymerase chain reaction (RT-PCR) and serologic testing. 377 patients with COPD attended 1,999 clinic visits and reported 310 exacerbations. There were 27 RSV-related exacerbations (8·7% of total); of these, seven were detected only on PCR, 16 only on serology and 4 by both methods. Increases in RSV specific N-protein antibody were as sensitive as antibody to pre-F or post-F for serodiagnosis of RSV related exacerbations. RSV is associated with 8.7% of outpatient managed COPD exacerbations in this study. Antibodies to RSV-N protein may have diagnostic value, potentially important in a vaccinated population. The introduction of vaccines that prevent RSV is expected to benefit patients with COPD.

Epidemiology and burden of respiratory syncytial virus in Italian adults: A systematic review and meta-analysis.

Respiratory syncytial virus (RSV) is a common respiratory pathogen not only in children, but also in adults. In view of a recent authorization of adult RSV vaccines in Italy, our research question was to quantify the epidemiology and burden of RSV in Italian adults. Observational studies on the epidemiology and clinical burden of laboratory-confirmed or record-coded RSV infection in Italian adults of any age were eligible. Studies with no separate data for Italian adults, modeling and other secondary publications were excluded. A literature search was performed in MEDLINE, Biological Abstracts, Global Health, Scopus and Web of Science on 22 November 2023. Critical appraisal was performed by means of a Joanna Briggs Institute checklist. Random-effects (RE) meta-analysis was performed to obtain pooled estimates and the observed heterogeneity was investigated by subgroup and meta-regression analyses. The protocol was prospectively registered (doi.org/10.17504/protocols.io.5qpvo32odv4o/v1). Thirty-five studies were identified, most of which had at least one possible quality concern. RSV seasonal attack rates ranged from 0.8 ‰ in community-dwelling older adults to 10.9% in hematological outpatients. In the RE model, 4.5% (95% CI: 3.2-5.9%) of respiratory samples tested positive for RSV. This positivity prevalence was higher in older adults (4.4%) than in working-age adults (3.5%) and in outpatient (4.9%) than inpatient (2.9%) settings. According to the meta-regression, study location and sample size were also significant predictors of RSV detection frequency. The pooled estimate of in-hospital mortality was as high as 7.2% (95% CI: 4.7-10.3%). Data on other indicators of the diseases burden, such as complication and hospitalization rates, were unavailable. RSV poses a measurable burden on Italian adults, especially those of older age and with some co-morbidities. However, several data on the natural history of RSV disease are missing and should be established by future large-scale studies.

Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase.

Estimates of the cost of medically attended lower respiratory tract illness (LRTI) due to respiratory syncytial virus (RSV) in adults, especially beyond the acute phase, is limited. This study was undertaken to estimate the attributable costs of RSV-LRTI among US adults during, and up to 1 year after, the acute phase of illness. A retrospective observational matched-cohort design and a US healthcare claims repository (2016-2019) were employed. The study population comprised adults aged ≥18 years with RSV-LRTI requiring hospitalization (RSV-H), an emergency department visit (RSV-ED), or physician office/hospital outpatient visit (RSV-PO/HO), as well as matched comparison patients. All-cause healthcare expenditures were tallied during the acute phase of illness (RSV-H: from admission through 30 days postdischarge; ambulatory RSV: during the episode) and long-term phase (end of acute phase to end of following 1-year period). The study population included 4526 matched pairs of RSV-LRTI and comparison patients (RSV-H: n = 970; RSV-ED: n = 590; RSV-PO/HO: n = 2966). Mean acute-phase expenditures were $42 179 for RSV-H (vs $5154 for comparison patients), $4409 for RSV-ED (vs $377), and $922 for RSV-PO/HO (vs $201). By the end of the 1-year follow-up period, mean expenditures-including acute and long-term phases-were $101 532 for RSV-H (vs $36 302), $48 701 for RSV-ED (vs $27 131), and $28 851 for RSV-PO/HO (vs $20 523); overall RSV-LRTI attributable expenditures thus totaled $65 230, $21 570, and $8327, respectively. The cost of RSV-LRTI requiring hospitalization or ambulatory care among US adults is substantial, and the economic impact of RSV-LTRI may extend well beyond the acute phase of illness.

The Annual Economic Burden of Respiratory Syncytial Virus in Adults in the United States

Abstract Background Current estimates of the economic burden of respiratory syncytial virus (RSV) are needed for policymakers to evaluate adult RSV vaccination strategies. Methods A cost-of-illness model was developed to estimate the annual societal burden of RSV in US adults aged ≥60 years. Additional analyses were conducted to estimate the burden of hospitalized RSV in all adults aged 50–59 years and in adults aged 18–49 years with potential RSV risk factors. Results Among US adults aged ≥60 years, the model estimated 4.0 million annual RSV cases (95% uncertainty interval [UI], 2.7–5.6 million) and an annual economic burden of $6.6 billion (95% UI, $3.1–$12.9 billion; direct medical costs, $2.9 billion; indirect costs, $3.7 billion). The 4% of RSV cases that were hospitalized contributed to 94% of direct medical costs. Additional analyses estimated $422 million in annual hospitalization costs among all adults aged 50–59 years. Among adults aged 18–49 years with RSV risk factors, annual per capita burden was highest among people with congestive heart failure at $51 100 per 1000 people. Discussion The economic burden of RSV is substantial among adults aged ≥50 years and among adults aged 18–49 years with RSV risk factors, underscoring the need for preventive interventions for these populations.

Clinical Phenotypes and Molecular Characteristics of Respiratory Syncytial Virus in Adults: A Monocentric Prospective Study Between 2019 and 2022.

Respiratory syncytial virus (RSV) infection is a major cause of pneumonia in adults. Little is known on the viral genetic diversity and the associated clinical phenotypes in this population. This single-center prospective cohort study included RSV-infected patients hospitalized between January 2019 and December 2022. Of 100 patients, including 41 with severe infection, 72 were infected with RSV-B. RSV genome sequencing showed no clustering according to severity. Patients infected with RSV-B with risk factors for severe pneumonia had significantly higher fusion protein diversity scores. No amino acid substitutions conferring resistance to nirsevimab were detected.

Evaluation of a stabilized RSV pre-fusion F mRNA vaccine: Preclinical studies and Phase 1 clinical testing in healthy adults

Human respiratory syncytial virus (RSV) causes a substantial proportion of respiratory tract infections worldwide. Although RSV reinfections occur throughout life, older adults, particularly those with underlying comorbidities, are at risk for severe complications from RSV. There is no RSV vaccine available to date, and treatment of RSV in adults is largely supportive. A correlate of protection for RSV has not yet been established, but antibodies targeting the pre-fusion conformation of the RSV F glycoprotein play an important role in RSV neutralization. We previously reported a Phase 1 study of an mRNA-based vaccine (V171) expressing a pre-fusion-stabilized RSV F protein (mDS-Cav1) in healthy adults. Here, we evaluated an mRNA-based vaccine (V172) expressing a further stabilized RSV pre-fusion F protein (mVRC1). mVRC1 is a single chain version of RSV F with interprotomer disulfides in addition to the stabilizing mutations present in the mDS-Cav1 antigen. The immunogenicity of the two mRNA-based vaccines encoding mVRC1 (V172) or a sequence-optimized version of mDS-Cav1 to improve transcriptional fidelity (V171.2) were compared in RSV-naïve and RSV-experienced African green monkeys (AGMs). V172 induced higher neutralizing antibody titers than V171.2 and demonstrated protection in the AGM challenge model. We conducted a Phase 1, randomized, placebo-controlled, clinical trial of 25 μg, 100 μg, 200 μg, or 300 μg of V172 in healthy older adults (60–79 years old; N = 112) and 100 μg, 200 μg, or 300 μg of V172 in healthy younger adults (18–49 years old; N = 48). The primary clinical objectives were to evaluate the safety and tolerability of V172, and the secondary objective was to evaluate RSV serum neutralization titers. The most commonly reported solicited adverse events were injection-site pain, injection-site swelling, headache, and tiredness. V172 was generally well tolerated in older and younger adults and increased serum neutralizing antibody titers, pre-fusion F-specific competing antibody titers, and RSV F-specific T-cell responses.

Burden of illness associated with Respiratory Syncytial Virus (RSV)-related hospitalizations among adults in Ontario, Canada: A retrospective population-based study

BackgroundGlobally, RSV is a common viral pathogen that causes 64 million acute respiratory infections annually. Our objective was to determine the incidence of hospitalization, healthcare resource use and associated costs of adults hospitalized with RSV in Ontario, Canada. MethodsTo describe the epidemiology of adults hospitalized with RSV, we used a validated algorithm applied to a population-based healthcare utilization administrative dataset in Ontario, Canada. We created a retrospective cohort of incident hospitalized adults with RSV between September 2010 and August 2017 and followed each person for up to two years. To determine the burden of illness associated with hospitalization and post-discharge healthcare encounters each RSV-admitted patient was matched to two unexposed controls based on demographics and risk factors. Patient demographics were described and mean attributable 6-month and 2-year healthcare costs (2019 Canadian dollars) were estimated. ResultsThere were 7,091 adults with RSV-associated hospitalizations between 2010 and 2019 with a mean age of 74.6 years; 60.4 % were female. RSV-coded hospitalization rates increased from 1.4 to 14.6 per 100,000 adults between 2010–2011 and 2018–2019. The mean difference in healthcare costs between RSV-admitted patients and matched controls was $28,260 (95 % CI: $27,728 - $28,793) in the first 6 months and $43,721 over 2 years (95 % CI: $40,383 – $47,059) post-hospitalization. ConclusionsRSV hospitalizations among adults increased in Ontario between 2010/11 to 2018/19 RSV seasons. RSV hospitalizations in adults were associated with increased attributable short-term and long-term healthcare costs compared to matched controls. Interventions that could prevent RSV in adults may reduce healthcare burden.

Leveraging Influenza Virus Surveillance From 2012 to 2015 to Characterize the Burden of Respiratory Syncytial Virus Disease in Canadian Adults ≥50 Years of Age Hospitalized With Acute Respiratory Illness.

Respiratory syncytial virus (RSV) disease in older adults is undercharacterized. To help inform future immunization policies, this study aimed to describe the disease burden in Canadian adults aged ≥50 years hospitalized with RSV. Using administrative data and nasopharyngeal swabs collected from active surveillance among adults aged ≥50 years hospitalized with an acute respiratory illness (ARI) during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, RSV was identified using a respiratory virus multiplex polymerase chain reaction test to describe the associated disease burden, incidence, and healthcare costs. Of 7797 patients tested, 371 (4.8%) were RSV positive (2.2% RSV-A and 2.6% RSV-B). RSV prevalence varied by season from 4.2% to 6.2%. Respiratory virus coinfection was observed in 11.6% (43/371) of RSV cases, with influenza A being the most common. RSV hospitalization rates varied between seasons and increased with age, from 8-12 per 100 000 population in adults aged 50-59 years to 174-487 per 100 000 in adults aged ≥80 years. The median age of RSV cases was 74.9 years, 63.7% were female, and 98.1% of cases had ≥1 comorbidity. Among RSV cases, the mean length of hospital stay was 10.6 days, 13.7% were admitted to the intensive care unit, 6.4% required mechanical ventilation, and 6.1% died. The mean cost per RSV case was $13 602 (Canadian dollars) but varied by age and Canadian province. This study adds to the growing literature on adult RSV burden by showing considerable morbidity, mortality, and healthcare costs in hospitalized adults aged ≥50 years with ARIs such as influenza.

Predicted Public Health and Economic Impact of Respiratory Syncytial Virus Vaccination with Variable Duration of Protection for Adults ≥60 Years in Belgium.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection (ARI) in older adults. This study used a static, cohort-based decision-tree model to estimate the public health and economic impact of vaccination against RSV in Belgians aged ≥60 years compared with no vaccination for different vaccine duration of protection profiles from a healthcare payer perspective. Three vaccine protection durations were compared (1, 3, and 5 years), and several sensitivity and scenario analyses were performed. Results showed that an RSV vaccine with a 3-year duration of protection would prevent 154,728 symptomatic RSV-ARI cases, 3688 hospitalizations, and 502 deaths over three years compared to no vaccination in older adults and would save EUR 35,982,857 in direct medical costs in Belgium. The number needed to vaccinate to prevent one RSV-ARI case was 11 for the 3-year duration profile, while it was 28 and 8 for the 1- and 5-year vaccine duration profiles, respectively. The model was generally robust in sensitivity analyses varying key input values. This study suggested that vaccination could substantially decrease the public health and economic burden of RSV in adults ≥60 years in Belgium, with benefits increasing with a longer duration of vaccine protection.

Diagnosis of Respiratory Syncytial Virus in Adults Substantially Increases When Adding Sputum, Saliva, and Serology Testing to Nasopharyngeal Swab RT-PCR.

Nearly all existing respiratory syncytial virus (RSV) incidence estimates are based on real-time polymerase chain reaction (RT-PCR) testing of nasal or nasopharyngeal (NP) swabs. Adding testing of additional specimen types to NP swab RT-PCR increases RSV detection. However, prior studies only made pairwise comparisons and the synergistic effect of adding multiple specimen types has not been quantified. We compared RSV diagnosis by NP swab RT-PCR alone versus NP swab plus saliva, sputum, and serology. This was a prospective cohort study over two study periods (27 December 2021 to 1 April 2022 and 22 August 2022 to 11 November 2022) of patients aged ≥ 40years hospitalized for acute respiratory illness (ARI) in Louisville, KY. NP swab, saliva, and sputum specimens were collected at enrollment and PCR tested (Luminex ARIES platform). Serology specimens were obtained at acute and convalescent timepoints (enrollment and 30-60-day visit). RSV detection rate was calculated for NP swab alone and for NP swab plus all other specimen type/test. Among 1766 patients enrolled, 100% had NP swab, 99% saliva, 34% sputum, and 21% paired serology specimens. RSV was diagnosed in 56 (3.2%) patients by NP swab alone, and in 109 (6.2%) patients by NP swab plus additional specimens, corresponding to a 1.95 times higher rate [95% confidence interval (CI) 1.62, 2.34]. Limiting the comparison to the 150 subjects with all four specimen types available (i.e., NP swab, saliva, sputum, and serology), there was a 2.60-fold increase (95% CI 1.31, 5.17) compared to NP swab alone (3.3% versus 8.7%). Sensitivities by specimen type were: NP swab 51%, saliva 70%, sputum 72%, and serology 79%. Diagnosis of RSV in adults was several-fold greater when additional specimen types were added to NP swab, even with a relatively low percentage of subjects with sputum and serology results available. Hospitalized RSV ARI burden estimates in adults based solely on NP swab RT-PCR should be adjusted for underestimation.

371. Adding sputum and saliva to nasopharyngeal swab samples for PCR detection of Respiratory Syncytial Virus in adults hospitalized with acute respiratory illness may double case detection

Abstract Background In hospitalized patients, nasopharyngeal (NP) swabs are the most common samples obtained for Respiratory Syncytial Virus (RSV) PCR testing. However, adding sputum is known to increase diagnostic yield, and saliva has been successfully used for viral respiratory infection diagnosis. We sought to compare RSV prevalence detected by PCR testing of NP swab alone versus NP swab plus saliva and sputum in adult patients hospitalized with acute respiratory illness (ARI). Methods This ongoing, prospective cohort study enrolled patients aged ≥40 years hospitalized for ARI in 4 hospitals in Louisville, Kentucky (Season 1: 27 Dec 21 – 1 Apr 22). NP swab, saliva, and sputum samples were obtained at enrollment or scavenged from standard-of-care specimens (all collected ≤3 days of admission), and PCR tested with Luminex ARIES FluA/B/RSV platform. We produced Venn diagrams of RSV positive samples by sample type for all patients and restricted to those with all 3 sample types. RSV prevalence for NP swab alone was calculated as number of patients with RSV-positive NP swabs divided by total number of patients tested. RSV prevalence by NP swab plus saliva and sputum was calculated as number of patients with RSV-positive NP swab, saliva, or sputum samples divided by total number of patients tested. Results We enrolled 653 patients and collected NP swabs (100% of patients), saliva (96%), and sputum (43% overall and 93% of the 303 sputum-producing patients). Among all patients, 28 patients tested RSV positive (Figure 1A), and when restricted to those with all 3 samples (Figure 1B), 14 tested positive. The overall cohort’s RSV prevalence by NP swab alone was 1.8% (12/653) and by NP swab plus saliva and/or sputum was 4.3% (28/653): 2.33 times higher with addition of saliva and sputum samples. Among patients with all 3 specimen types, the RSV prevalence increase was the same, and none were positive by NP swab only. Figure 1.Venn diagrams of positive RSV PCR tests (Left) A. Positive RSV PCR tests for 653 patients in overall cohort (Right) B. Positive RSV PCR tests for 275 patients with all 3 samples obtained. Conclusion RSV was most commonly detected in saliva samples. Current standard-of-care utilizing NP swab for RSV PCR testing appears to underestimate true RSV prevalence in hospitalized adult patients with ARI by more than 2-fold. Disclosures Alan Junkins, PhD, D(ABMM), Biomerieux: Advisor/Consultant Paul S. Schulz, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria Robin Hubler, MS, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds|Pfizer, Inc: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds|Pfizer, Inc: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: I am a full time employee of Pfizer and hold Pfizer stocks Bradford D. Gessner, M.D., M.P.H., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds.

2208. Rates of Medically-Attended RSV among US Adults: A Systematic Review and Meta-Analysis

Abstract Background Adult respiratory syncytial virus (RSV) vaccines are in late stages of development. A comprehensive synthesis of adult RSV burden is needed to inform public health decision-making. Methods We performed a systematic review and meta-analysis of studies describing the incidence of medically-attended RSV (MA-RSV) among US adults. We also identified studies reporting nasopharyngeal (NP) or nasal swab RT-PCR results with paired serology (four-fold-rise) or sputum (RT-PCR) to calculate RSV detection ratios quantifying improved diagnostic yield after adding a second specimen type (ie, serology or sputum). Results We identified 14 studies with 15 unique MA-RSV incidence estimates, all based on NP or nasal swab RT-PCR testing alone. Pooled annual RSV-associated incidence per 100,000 adults ≥65 years of age was 178 (95%CI: 152‒204; n=8 estimates) hospitalizations (4 prospective studies: 189; 4 model-based studies: 157), 133 (95%CI: 0‒319, n=2) emergency department (ED) admissions, and 1519 (95%CI: 1109‒1929, n=3) outpatient visits. Based on 6 studies, RSV detection was ∼1.5 times higher when adding paired serology or sputum. After adjustment for this increased yield, annual RSV-associated rates per 100,000 adults ≥65 years were 267 hospitalizations (UI: 228‒306) (prospective: 282; model-based: 236), 200 ED admissions (UI: 0‒478), and 2278 outpatient visits (UI: 1663‒2893). Persons &amp;lt; 65 years with chronic medical conditions were 1.2−28 times more likely to be hospitalized for RSV depending on risk condition. Conclusion The true burden of RSV has been underestimated and is significant among older adults and individuals with chronic medical conditions. A highly effective adult RSV vaccine would have substantial public-health impact. Disclosures John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Farid L. Khan, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds David Swerdlow, MD, Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds Luis Jodar, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Ann R. Falsey, MD, BioFire Diagnostics: Grant/Research Support|Janssen: Grant/Research Support|Merck, Sharp and Dohme: Grant/Research Support|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support.

LB745. Respiratory Syncytial Virus (RSV) Prefusion F Protein Candidate Vaccine (RSVPreF3 OA) is Efficacious in Adults ≥ 60 Years of Age (YOA)

Abstract Background RSV-associated acute respiratory infections (ARI), particularly lower respiratory tract diseases (LRTD), present a significant disease burden in older adults. Currently, there are no approved vaccines against RSV. We present results from an ongoing study designed to demonstrate the vaccine efficacy (VE) of the AS01E-adjuvanted RSVPreF3 OA in adults ≥ 60 YOA. Methods This ongoing, phase 3, observer-blind, placebo-controlled, multi-country study (NCT04886596) enrolled adults ≥ 60 YOA from the northern and southern hemispheres. Participants were randomized (1:1) to receive a single dose of RSVPreF3 OA or placebo before the RSV season. The primary objective was to demonstrate VE of a single dose of RSVPreF3 OA in preventing RSV-confirmed LRTD during one RSV season (criterion: lower limit of VE confidence interval [CI] &amp;gt; 20%). VE is reported also against severe RSV-confirmed LRTD, RSV-confirmed ARI, RSV-confirmed LRTD and RSV-confirmed ARI by RSV subtype (RSV-A and RSV-B), and RSV-confirmed LRTD by age, baseline comorbidity and frailty status. RSV-A/B was confirmed by quantitative RT-PCR. Results A total of 26,664 participants were enrolled, of whom 24,966 (RSVPreF3 OA: 12,467; placebo: 12,499) were included in the exposed set and 24,960 (RSVPreF3 OA: 12,466; placebo: 12,494) in the efficacy analysis. The mean age was 69.5 (±6.5) years and 51.7% were women. Over a median follow-up of 6.7 months (maximum 10.1 months), 47 RSV-confirmed LRTD episodes were reported (RSVPreF3 OA: 7; placebo: 40), resulting in a VE of 82.6% (96.95% CI: 57.9–94.1), thus the primary objective was met. Consistently high VE across the clinical spectrum of RSV disease, from RSV-confirmed ARI (71.7% [95% CI: 56.2–82.3]) to severe RSV-confirmed LRTD (94.1% [95% CI: 62.4–99.9]) was observed. High VE was seen in different age groups and regardless of RSV subtype, baseline comorbidity or pre-frail status (Figure 1). Cumulative incidence curves for RSV-confirmed LRTD and RSV-confirmed ARI showed persistent efficacy throughout the follow-up (Figure 2). Conclusion A single RSVPreF3 OA dose is highly efficacious against RSV-confirmed LRTD and RSV-confirmed ARI in adults ≥ 60 YOA, regardless of RSV disease severity, RSV subtype, baseline comorbidity and pre-frail status. Funding: GlaxoSmithKline Biologicals SA. Abstract and information is also available at the following link : Efficacy results for GSK's older adult RSV vaccine (investis.com). Disclosures Michael G. Ison, MD MS, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support Alberto Papi, MD, CHIESI, ASTRAZENECA, GSK, BI, MENARINI, NOVARTIS, ZAMBON, MUNDIPHARMA, SANOFI, AVILLION: Honoraria|CHIESI, ASTRAZENECA, GSK, NOVARTIS, SANOFI, IQVIA, AVILLION, ELPEN PHARMACEUTICALS: Advisor/Consultant|CHIESI, ASTRAZENECA, GSK, NOVARTIS, SANOFI, IQVIA, AVILLION, ELPEN PHARMACEUTICALS: Board Member|CHIESI, ASTRAZENECA, GSK, SANOFI: Grant/Research Support Joanne M. Langley, MD, GSK, Merck, Medicago, Sanofi, VBI, VIDO, Entos, Pfizer: Grant/Research Support Isabel Leroux-Roels, PhD MD, Curevac: payment to my institution for the conduct of clinical trials|GSK: payment to my institution for the conduct of clinical trials|ICON Genetics: payment to my institution for the conduct of clinical trials|Janssen Vaccines (J&amp;J): Board Member|Janssen Vaccines (J&amp;J): payment to my institution for the conduct of clinical trials|Osivax: payment to my institution for the conduct of clinical trials Federico Martinon-Torres, MD, PhD, Assoc. Prof, GlaxoSmithKline, Pfizer, Sanofi, Merck, Moderna, Astra Zeneca, Biofabri, Janssen, Novavax: Advisor/Consultant|GlaxoSmithKline, Pfizer, Sanofi, Merck, Moderna, Astra Zeneca, Biofabri, Janssen, Novavax: Grant/Research Support|GlaxoSmithKline, Pfizer, Sanofi, Merck, Moderna, Astra Zeneca, Biofabri, Janssen, Novavax: Honoraria|GlaxoSmithKline, Pfizer, Sanofi, Merck, Moderna, Astra Zeneca, Biofabri, Janssen, Novavax: Clínical trials fees paid to my institution Tino F. Schwarz, Prof. Dr. MD, GlaxoSmithKline: Advisor/Consultant Richard N. Van Zyl-Smit, PhD MD, MSD, Pfizer, GSK, Astra Zeneca, Roche, Novartis, Boehringer Ingelheim, Cipla, J&amp;J, Glenmark: Advisor/Consultant|MSD, Pfizer, GSK, Astra Zeneca, Roche, Novartis, Boehringer Ingelheim, Cipla, J&amp;J, Glenmark: Honoraria Nancy Dezutter, PhD, PharmD, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Nathalie De Schrevel, PhD, GlaxoSmithKline: GSK employee Laurence Fissette, Master in Statistics, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Marie-Pierre David, Master in Statistics, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Marie Van Der Wielen, MD, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Lusine Kostanyan, MD, GlaxoSmithKline: GSK employee|GlaxoSmithKline: Stocks/Bonds Veronica Hulstrøm, PhD MD, GlaxoSmithKline: GSK employee.

EE63 Economic Burden of Respiratory Syncytial Virus in Adults in the United States

EE63 Economic Burden of Respiratory Syncytial Virus in Adults in the United States

EE490 Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase

EE490 Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase

Modelled estimates of hospitalisations attributable to respiratory syncytial virus and influenza in Australia, 2009-2017.

Respiratory syncytial virus (RSV) and influenza are important causes of disease in children and adults. In Australia, information on the burden of RSV in adults is particularly limited. We used time series analysis to estimate respiratory, acute respiratory infection, pneumonia and influenza, and bronchiolitis hospitalisations attributable to RSV and influenza in Australia during 2009 through 2017. RSV and influenza-coded hospitalisations in &lt;5-year-olds were used as proxies for relative weekly viral activity. From 2009 to 2017, the estimated all-age average annual rates of respiratory hospitalisations attributable to RSV and seasonal influenza (excluding 2009) were 54.8 (95% confidence interval [CI]: 20.1, 88.8) and 87.8 (95% CI: 74.5, 97.7) per 100,000, respectively. The highest estimated average annual RSV-attributable respiratory hospitalisation rate per 100,000 was 464.2 (95% CI: 285.9, 641.2) in &lt;5-year-olds. For seasonal influenza, it was 521.6 (95% CI: 420.9, 600.0) in persons aged ≥75 years. In ≥75-year-olds, modelled estimates were approximately eight and two times the coded estimates for RSV and seasonal influenza, respectively. RSV and influenza are major causes of hospitalisation in young children and older adults in Australia, with morbidity underestimated by hospital diagnosis codes.

Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta-analysis

BackgroundAdult respiratory syncytial virus (RSV) vaccines are in the late stages of development. A comprehensive synthesis of adult RSV burden is needed to inform public health decision-making.MethodsWe performed a systematic review and meta-analysis of studies describing the incidence of medically attended RSV (MA-RSV) among US adults. We also identified studies reporting nasopharyngeal (NP) or nasal swab reverse transcription polymerase chain reaction (RT-PCR) results with paired serology (4-fold-rise) or sputum (RT-PCR) to calculate RSV detection ratios quantifying improved diagnostic yield after adding a second specimen type (ie, serology or sputum).ResultsWe identified 14 studies with 15 unique MA-RSV incidence estimates, all based on NP or nasal swab RT-PCR testing alone. Pooled annual RSV-associated incidence per 100 000 adults ≥65 years of age was 178 (95% CI, 152‒204; n = 8 estimates) hospitalizations (4 prospective studies: 189; 4 model-based studies: 157), 133 (95% CI, 0‒319; n = 2) emergency department (ED) admissions, and 1519 (95% CI, 1109‒1929; n = 3) outpatient visits. Based on 6 studies, RSV detection was ∼1.5 times higher when adding paired serology or sputum. After adjustment for this increased yield, annual RSV-associated rates per 100 000 adults age ≥65 years were 267 hospitalizations (uncertainty interval [UI], 228‒306; prospective: 282; model-based: 236), 200 ED admissions (UI, 0‒478), and 2278 outpatient visits (UI, 1663‒2893). Persons <65 years with chronic medical conditions were 1.2−28 times more likely to be hospitalized for RSV depending on risk condition.ConclusionsThe true burden of RSV has been underestimated and is significant among older adults and individuals with chronic medical conditions. A highly effective adult RSV vaccine would have substantial public health impact.