Burkart Katrin, Liang Caihua, Rafferty Quinn, Gillespie Catherine W, McLaughlin Susan, Oros Andrei, Suba Jam, Bruno Duilia, Fahey Marion, Grajales Ana G, Haeberer Mariana, Lade Caroline, Yoshida Asuka, Gessner Bradford D, Begier Elizabeth
Institute for Health Metrics and Evaluation, University of Washington, Seattle, USA.
Global Medical Development, Scientific and Clinical Affairs, Pfizer Inc., Collegeville, PA, USA.
EClinicalMedicine. 2025 Jun 16;85:103292. doi: 10.1016/j.eclinm.2025.103292. eCollection 2025 Jul.
Respiratory syncytial virus (RSV) in adults is typically underdiagnosed due to non-specific symptoms, infrequent routine testing, and low-test sensitivity; consequently, its impact is not well understood. To address this gap, we developed a novel approach to estimate adult RSV-related hospitalizations, leveraging methods from the Global Burden of Disease (GBD) study.
We collected aggregated clinical data from hospital statistics and insurance claims on respiratory and cardiorespiratory hospitalizations and RSV activity proxies for age groups 18-59 years, 60-74 years, ≥60 years, and ≥75 years in 15 countries (Argentina, Brazil, Canada, Chile, Georgia, Germany, Greece, Ireland, Italy, Japan, Mexico, New Zealand, Poland, Spain, and the United States) between 1992 and 2021. In addition, we collected RSV surveillance data, i.e., the percentage of samples tested positive for RSV from the WHO GISRS platform-the Global Influenza Surveillance and Response System and from country-specific reporting platforms for countries from North and South America, Europe and Asia, covering the years 2015-2023. Using the GBD comparative risk assessment framework, we estimated exposure-response relationships between RSV activity and hospitalizations using generalized additive models (GAMs), adjusting for trend, seasonality, meteorological influence and influenza activity, between the years 2015-2019, and calculated the population attributable fraction (PAF) and RSV-attributable hospitalizations. We evaluated the predictive power of surveillance-based versus hospital-based RSV proxies based on adjusted R, and generalized cross-validation (GCV) score.
We identified significant relationships (p-value < 0.01) between RSV activity and increased respiratory and cardiorespiratory hospitalizations among adults. Generally, hospital-based RSV proxies predicted hospitalization better than surveillance-based proxies. RSV-attributable hospitalization rates and PAFs varied substantially by age and country. The highest annual RSV-attributable hospitalization rates were estimated for individuals 75 years and older, ranging from 110.9 (95% uncertainty interval [UI]: 66.9-156.1, median: 113.5, inter quartile range [IQR]: 10.4) per 100,000 population in Argentina for respiratory hospitalizations to 1199.8 (1087.0-1313.8, 1209.5, 88.9) per 100,000 in New Zealand for cardiorespiratory hospitalizations. The lowest RSV-attributable hospitalizations, for respiratory and cardiorespiratory diseases, were found for adults aged 18-59 years in Spain with 5.0 (95% UI: 0.8-9.3) hospitalizations per 100,000 for the hospital-based proxy.
Innovations introduced by this analysis include non-parametric modelling of the exposure-response relationship between RSV activity and hospitalizations and evaluating the predictive reliability of two RSV proxies. Our findings highlight the substantial adult RSV disease burden, provide estimates for countries with no prior data (particularly those in (sub)tropical climates such as Mexico and Brazil), and illustrate the considerable geographic variability in adult RSV incidence. These results can guide future research, interventions, and policy decisions, including those involving adult RSV vaccines.
This study was sponsored by Pfizer Inc.
由于症状不具特异性、常规检测频率低以及检测灵敏度不高，成人呼吸道合胞病毒（RSV）感染通常诊断不足；因此，其影响尚未得到充分了解。为填补这一空白，我们采用了一种新方法，利用全球疾病负担（GBD）研究中的方法来估算成人RSV相关住院病例数。
我们收集了1992年至2021年间15个国家（阿根廷、巴西、加拿大、智利、格鲁吉亚、德国、希腊、爱尔兰、意大利、日本、墨西哥、新西兰、波兰、西班牙和美国）18 - 59岁、60 - 74岁、≥60岁和≥75岁年龄组的呼吸道和心肺住院病例以及RSV活动指标的医院统计数据和保险理赔汇总临床数据。此外，我们收集了RSV监测数据，即来自世卫组织全球流感监测和应对系统（GISRS）平台以及北美、南美、欧洲和亚洲各国特定报告平台的RSV检测呈阳性样本的百分比，涵盖2015 - 2023年。利用GBD比较风险评估框架，我们使用广义相加模型（GAMs）估计了2015 - 2019年间RSV活动与住院病例之间的暴露 - 反应关系，并对趋势、季节性、气象影响和流感活动进行了调整，计算了人群归因分数（PAF）和RSV归因住院病例数。我们基于调整后的R值和广义交叉验证（GCV）分数评估了基于监测的RSV指标与基于医院的RSV指标的预测能力。
我们发现RSV活动与成人呼吸道和心肺住院病例增加之间存在显著关系（p值<0.01）。一般来说，基于医院的RSV指标比基于监测的指标对住院病例的预测效果更好。RSV归因住院率和PAF在不同年龄和国家之间差异很大。估计75岁及以上人群的年度RSV归因住院率最高，从阿根廷每10万人口中因呼吸道住院的110.9（95%不确定区间[UI]：66.9 - 156.1，中位数：113.5，四分位间距[IQR]：10.4）到新西兰每10万人口中心肺住院的1199.8（1087.0 - 1313.8，1209.5，88.9）不等。西班牙18 - 59岁成年人因呼吸道和心肺疾病的RSV归因住院病例数最低，基于医院的指标为每10万人口中有5.0（95% UI：0.8 - 9.3）例住院。
本分析引入的创新包括对RSV活动与住院病例之间的暴露 - 反应关系进行非参数建模，以及评估两种RSV指标的预测可靠性。我们的研究结果突出了成人RSV疾病的巨大负担，为没有先前数据的国家（特别是墨西哥和巴西等（亚）热带气候国家）提供了估计，并说明了成人RSV发病率在地理上的显著差异。这些结果可为未来的研究、干预措施和政策决策提供指导，包括那些涉及成人RSV疫苗的决策。
本研究由辉瑞公司赞助。
