Background: Adult 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. 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 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). 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 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. Conclusions: 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.

Background: Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection. Methods: EMBASE, PubMed, and Web of Science were searched (January 2000−December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types. Results: Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable. Conclusions: RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates.

: Identification of risk factors for severe respiratory syncytial virus (RSV) disease in adults could facilitate their appropriate vaccine recommendations. We conducted a systematic literature review (last 10 years in PubMed/Embase) to identify quantitative estimates of risk factors for severe RSV infection outcomes in high-income countries. Severe outcomes from RSV infection included hospitalization, excess mortality, lower respiratory tract infection, or a composite measure: severe RSV, which included these outcomes and others, such as mechanical ventilation and extended hospital stay. Among 1494 articles screened, 26 met eligibility criteria. We found strong evidence that the following increased the risk of severe outcomes: age, preexisting comorbid conditions (eg, cardiac, pulmonary, and immunocompromising diseases, as well as diabetes and kidney disease), and living conditions (socioeconomic status and nursing home residence). The frequency of severe outcomes among younger adults with comorbidities was generally similar to that experienced by older adults, suggesting that immunosenescence and chronic conditions are both contributing factors for elevated risk. Trial registration: PROSPERO (CRD42022315239).

Introduction: Respiratory syncytial virus (RSV) is an important cause of severe respiratory illness in older adults and adults with respiratory or cardiovascular comorbidities. Published estimates of its incidence and prevalence in adult groups vary widely. This article reviews the potential limitations affecting RSV epidemiology studies and suggests points to consider when evaluating or designing them. Methods: Studies reporting the incidence or prevalence of RSV infection in adults in high-income Western countries from 2000 onwards were identified via a rapid literature review. Author-reported limitations were recorded, together with presence of other potential limitations. Data were synthesized narratively, with a focus on factors affecting incidence estimates for symptomatic infection in older adults. Results: A total of 71 studies met the inclusion criteria, most in populations with medically attended acute respiratory illness (ARI). Only a minority used case definitions and sampling periods tailored specifically to RSV; many used influenza-based or other criteria that are likely to result in RSV cases being missed. The great majority relied solely on polymerase chain reaction (PCR) testing of upper respiratory tract samples, which is likely to miss RSV cases compared with dual site sampling and/or addition of serology. Other common limitations were studying a single season, which has potential for bias due to seasonal variability; failure to stratify results by age, which underestimates the burden of severe disease in older adults; limited generalizability beyond a limited study setting; and absence of measures of uncertainty in the reporting of results. Conclusions: A significant proportion of studies are likely to underestimate the incidence of RSV infection in older adults, although the effect size is unclear and there is also potential for overestimation. Well-designed studies, together with increased testing for RSV in patients with ARI in clinical practice, are required to accurately capture both the burden of RSV and the potential public health impact of vaccines.

Introduction Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI)-related hospitalizations in older adults. Without RSV-specific treatment for adults, testing is uncommon, leading to potential underestimation of RSV incidence in real-world data studies. This study aimed to quantify the frequency of RSV testing during LRTI-related hospitalizations of older adults to inform interpretation of incidence estimates. Methods Administrative and billing data for hospitalizations of adults aged ≥ 65 years with a primary or secondary diagnosis of LRTI during the 2016–2019 RSV seasons (October–April) were extracted from the US all-payer Premier Healthcare Database (PHD). Billing codes identified RSV tests administered during eligible hospitalizations. The proportion of LRTI-related hospitalizations with a billed RSV test was calculated for each hospital in PHD, and summarized descriptively by hospital bed size, teaching status, and population served. Results Most of the 937 study hospitals performed RSV testing infrequently during LRTI hospitalization; median percentage of LRTI hospitalizations with RSV testing was 4.3%, and 78.4% of hospitals performed RSV testing in less than 25% of LRTI-related hospitalizations. RSV testing varied extensively by hospital type. Median percentage tested was significantly higher for hospitals with ≥ 200 beds (9.1%) versus < 200 beds (1.6%), for teaching (11.0%) versus non-teaching (2.5%) hospitals, and in urban (7.4%) versus rural (0.7%) settings. The median percentage of RSV testing increased over time, from 0.8% to 6.3% between the 2016/17 and 2018/19 seasons. Conclusion A small proportion of older adults hospitalized with LRTI are tested for RSV in US hospitals. Large variability occurs across hospital types. Consequently, retrospective database analyses likely result in a substantial underestimation of the true RSV-related hospitalization incidence. RSV incidence studies using real-world data need to assess for RSV testing frequency and adjust their results for under ascertainment associated with limited testing.

Introduction Understanding the differences between respiratory syncytial virus (RSV) subgroups A and B provides insights for the development of prevention strategies and public health interventions. We aimed to describe the structural differences of RSV subgroups, their epidemiology, and genomic diversity. The associated immune response and differences in clinical severity were also investigated. Methods A literature review from PubMed and Google Scholar (1985–2023) was performed and extended using snowballing from references in captured publications. Results RSV has two major antigenic subgroups, A and B, defined by the G glycoprotein. The RSV F fusion glycoprotein in the prefusion conformation is a major target of virus neutralizing antibodies and differs in surface exposed regions between RSV A and RSV B. The subgroups co-circulate annually, but there is considerable debate as to whether clinical severity is impacted by the subgroup of the infecting RSV strain. Large variations between the studies reporting RSV subgroup impact on clinical severity were observed. A tendency for higher disease severity may be attributed to RSV A but no consensus could be reached as to whether infection by one of the subgroup caused more severe outcomes. RSV genotype diversity decreased over the last two decades, and ON and BA have become the sole lineages detected for RSV A and RSV B, since 2014. No studies with data obtained after 2014 reported a difference in disease severity between the two subgroups. RSV F is relatively well conserved and highly similar between RSV A and B, but changes in the amino acid sequence have been observed. Some of these changes led to differences in F antigenic sites compared to reference F sequences (e.g., RSV/A Long strain), which are more pronounced in antigenic sites of the prefusion conformation of RSV B. Initial results from the second season after vaccination suggest specific RSV B efficacy wanes more rapidly than RSV A for RSV PreF-based monovalent vaccines. Conclusions RSV A and RSV B both contribute substantially to the global RSV burden. Both RSV subgroups cause severe disease and none of the available evidence to date suggests any differences in clinical severity between the subgroups. Therefore, it is important to implement measures effective at preventing disease due to both RSV A and RSV B to ensure impactful public health interventions. Monitoring overtime will be needed to assess the impact of waning antibody levels on subgroup-specific efficacy.