Adjusting for Case Under-Ascertainment in Estimating RSV Hospitalisation Burden of Older Adults in High-Income Countries: a Systematic Review and Modelling Study

Introduction: Previous studies suggest diagnostic testing characteristics (i.e. variations in clinical specimens and diagnostic tests) can contribute to underestimation of RSV disease burden. We aimed to improve the understanding of RSV hospitalisation burden in older adults (aged ≥ 65 years) in high-income countries through adjusting for case under-ascertainment.

Methods: We conducted a systematic review to include data on RSV-associated acute respiratory infection (ARI) hospitalisation burden in older adults in high-income countries. To adjust for case under-ascertainment, we developed a two-step framework that incorporated empirical data on the RSV detection proportion of different clinical specimens and testing approaches as well as their statistical uncertainty. We estimated the unadjusted and adjusted RSV-associated hospitalisation burden through multilevel random-effects meta-analysis. We further explored RSV-associated in-hospital mortality burden.

Results: We included 12 studies with eligible RSV hospitalisation burden data. We estimated that pooled unadjusted hospitalisation rate was 157 per 100,000 (95% CI 98-252) for adults aged ≥ 65 years; the rate was adjusted to 347 per 100,000 (203-595) after accounting for under-ascertainment. The adjusted rate could be translated into 787,000 (460,000-1,347,000) RSV-associated hospitalisations in high-income countries in 2019, which was about 2.2 times the unadjusted estimate. Stratified analysis by age group showed that the adjusted rate increased with age, from 231 per 100,000 in adults aged 65-74 years to 692 per 100,000 in adults aged > 85 years. The in-hospital case fatality ratio of RSV was 6.1% (3.3-11.0) and the total RSV-associated in-hospital deaths in high-income countries in 2019 could be between 22,000 and 47,000.

Conclusion: This study improves the understanding of RSV-associated hospitalisation burden in older adults and shows that the true RSV-associated hospitalisation burden could be 2.2 times what was reported in existing studies. This study has implications for calculating the benefit of interventions to treat and prevent RSV-associated disease.