Meta-analysis finds RSV outcomes peak in early infancy in low- and middle-income countries

BACKGROUND: Low-income and middle-income countries (LMICs) bear the greatest burden of respiratory syncytial virus (RSV) disease. WHO recommends passive immunisation to protect infants younger than 6 months and, in some strategies, infants up to age 12 months, but detailed age data are needed to determine optimal timing and impact. Our study estimates age distributions for the full range of RSV outcomes among children younger than 5 years in LMICs. METHODS: We conducted a systematic review and meta-analysis of RSV age distributions for seven health or health-care outcomes (hereafter, RSV outcomes): community cases, outpatient or clinic visits, emergency room visits, inpatient ward admissions, intensive care unit (ICU) admissions, facility deaths, and non-facility deaths. Inclusion required at least 30 laboratory-confirmed counts of RSV disease in children younger than 5 years, for a single RSV outcome from a single LMIC in the pre-COVID-19 decade (Jan 1, 2010, to Dec 31, 2019). We invited authors of included studies to share RSV counts by week or month of age. Using a Bayesian hierarchical model, we fitted parametric age distributions (by week for children <5 years) to each dataset, and derived pooled estimates of the mode, median, and mean age for each RSV outcome. The study was registered with PROSPERO (CRD42023435080). FINDINGS: We included 160 datasets with 131 124 RSV counts in children younger than 5 years. The mode (peak) age was 3 weeks (95% credible interval 1-6) for non-facility deaths (57% <6 months), 4 weeks (1-8) for facility deaths (57% <6 months), 7 weeks (6-8) for ICU admissions (60% <6 months), 17 weeks (14-19) for inpatient ward admissions (41% <6 months), 10 weeks (5-17) for emergency room visits (40% <6 months), 28 weeks (22-32) for outpatient or clinic visits (19% <6 months), and 22 weeks (17-28) for community cases (26% <6 months). Considering the most severe RSV outcomes, 20% of ICU admissions and 23% of facility deaths were in infants younger than 8 weeks. INTERPRETATION: Our findings reaffirm the importance of immunising the youngest infants who bear the greatest burden of severe RSV outcomes. Our estimates should allow more precise quantification of the potential impact of RSV prevention strategies across the full range of RSV disease severity in children younger than 5 years. FUNDING: WHO.