Understanding the age spectrum of respiratory syncytial virus associated hospitalisation and mortality burden based on statistical modelling methods: a systematic analysis

Abstract

Background: Statistical modelling studies based on excess morbidity and mortality are important for understanding RSV disease burden for age groups that are less frequently tested for RSV. We aimed to understand the full age spectrum of RSV morbidity and mortality burden based on statistical modelling studies, as well as the value of modelling studies in RSV disease burden estimation.

Methods: The databases Medline, Embase and Global Health were searched to identify studies published between January 1, 1995, and December 31, 2021, reporting RSV-associated excess hospitalisation or mortality rates of any case definitions using a modelling approach. All reported rates were summarised using median, IQR (Interquartile range) and range by age group, outcome and country income group; where applicable, a random-effects meta-analysis was conducted to combine the reported rates. We further estimated the proportion of RSV hospitalisations that could be captured in clinical databases.

Results: A total of 32 studies were included, with 26 studies from high-income countries. RSV-associated hospitalisation and mortality rates both showed a U-shape age pattern. Lowest and highest RSV acute respiratory infection (ARI) hospitalisation rates were found in 5-17 years (median: 1.6/100,000 population, IQR: 1.3-18.5) and < 1 year (2235.7/100,000 population, 1779.1-3552.5), respectively. Lowest and highest RSV mortality rates were found in 18-49 years (0.1/100,000 population, 0.06-0.2) and ≥ 75 years (80.0/100,000 population, 70.0-90.0) for high-income countries, respectively, and in 18-49 years (0.3/100,000 population, 0.1-2.4) and < 1 year (143.4/100,000 population, 143.4-143.4) for upper-middle income countries. More than 70% of RSV hospitalisations in children < 5 years could be captured in clinical databases whereas less than 10% of RSV hospitalisations could be captured in adults, especially for adults ≥ 50 years. Using pneumonia and influenza (P&I) mortality could potentially capture half of all RSV mortality in older adults but only 10-30% of RSV mortality in children.

Conclusions: Our study provides insights into the age spectrum of RSV hospitalisation and mortality. RSV disease burden using laboratory records alone could be substantially severely underreported for age groups ≥ 5 years. Our findings confirm infants and older adults should be prioritised for RSV immunisation programmes.

Trial registration: PROSPERO CRD42020173430.

Keywords: Burden of disease; Hospitalisation; Model; Mortality; Respiratory syncytial virus; Systematic reviews.

Fig. 1

PRISMA diagram for selection of studies

Fig. 2

Median, IQR and ranges of reported estimates of rates of RSV-associated hospitalisation in high-income countries. ALRI, acute lower respiratory infection; ARI, acute respiratory infection; C&R, circulatory and respiratory; CRD, chronic respiratory infection; P&I, pneumonia and influenza. Y-axis is displayed in log scale. The dotted line is used for distinguishing the estimates for broader age groups from finer age groups. Number at the bottom of each panel indicates number of data-points, if studies reported estimates for multiple years or seasons, then this study contributes to multiple data points. This data is available in Additional file 1: Tables S5-S6, S8-10

Fig. 3

Comparison of modelled and recorded estimates by age group for studies reporting RSV-associated hospitalisation rates. The y-axis represents the ratio of recorded estimates to modelled estimates and is displayed in log scale. Number at the bottom of indicates number of data-points, if studies reported estimates for multiple years or seasons, then this study contributes to multiple data points. Recorded estimates, also called directly observed number/rate, represents hospital admissions with laboratory confirmed virus infection. Modelled estimates represent hospital admissions rate estimated from statistical models

Fig. 4

Median, IQR and ranges of reported estimates of rates of RSV-associated mortality. ARI, acute respiratory infection; C&R, circulatory and respiratory; P&I, pneumonia and influenza. Y-axis is displayed in log scale. The dotted line is used for distinguishing the estimates for broader age groups from finer age groups. Number at the bottom of each panel indicates number of data-points, if studies reported estimates for multiple years or seasons, then this study contributes to multiple data points. This data is available in Additional file 1: Tables S4-5, S7-9, 11–13