Population-based serology reveals risk factors for RSV infection in children younger than 5 years

Abstract

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization in infants. Underlying risk factors for RSV infection in the general population are not well understood, as previous work has focused on severe outcomes of infection in a clinical setting. Here we use RSV-specific IgG and IgA antibody measurements from two population-based cross-sectional serosurveys carried out in the Netherlands (n = 682) to classify children up to 5 years as seronegative or seropositive. We employ a generalized additive model to estimate the probability of prior RSV infection as function of age, date of birth within the year, and other risk factors. The analyses show that the majority of children have experienced a RSV infection before the age of 2 years. Age and birthdate are strong predictors of RSV infection in the first years of life, and children born in summer have higher estimated probability of infection than those born in winter [e.g., 0.56 (95% CI 0.45-0.66) vs. 0.32 (0.21-0.45) at age 1 year]. Our analyses reveal that the mean age at infection depends on date of birth, which has implications for the design of vaccination programmes and prioritisation schemes for the prophylactic use of monoclonal antibodies.

Figure 1

IgG and IgA concentrations as a function of age. Scatter diagram showing the IgG concentration as a function of age, and coloured by IgA concentration for three antigens, prefusion F (left-hand panel), postfusion F (middle panel), and N (right-hand panel).

Figure 2

Dependence of infection status on age and date of birth within the year. (A) Bar chart (top) and proportional bar chart (bottom) showing the total number of samples (green), and fractions that are classified as infected (orange) and uninfected (blue). (B,C) Lexis diagrams of infection status of infants under 12 months of age in the 2006/2007 and 2016/2017 cohorts (see Supplement Figure 3 for full age range). Left-hand y-axes correspond to individual life histories. Individuals are born at the green dots, and sampled at the orange (infected) and blue (uninfected) dots, respectively. Right-hand Y-axes correspond to the histograms of the weekly number of positive RSV tests in hospitals in the Netherlands, representing the RSV epidemics.

Figure 3

Estimates of the probability of prior infection as function of age and birth DOY. Panels show the estimated probability of prior infection as function of birth DOY within the years for various ages (baseline model). Shaded areas represent 95% confidence envelopes. See Supplement Figure 4 for additional results.

Figure 4

Estimates of the probability of prior infection as function of age, birth DOY, and risk factors. Shown is the estimated probability of prior infection as function of birth DOY within the year for various ages and for living with or without a young sibling (siblings0–4). Colours indicate visiting a day-care and shaded areas represent 95% confidence envelopes.