Strengths and weaknesses
Our study has several strengths. First, it is based on a large population of children and adults covering a wide range of ages (range: 2-80), with detailed assessment of both RSV and RV-specific IgG levels and personal factors. Moreover, this population includes a subpopulation of individuals with respiratory viruses IgG assessment in both childhood and early adulthood allowing to specifically characterize change in IgG levels at the individual level over time. Novel and validated micro-array techniques were used to assess IgG levels. Then, different antigens were studied, related to two different respiratory viruses, RSV and RV. For RV, the analyses were based on micro-arrayed VP1 N-terminal peptides from a panel of the most representative RV strains covering the three genetic species.
We acknowledge that our study also suffers from some limitations. First, we did not have any information about the number of infections or the time at which viral infection occurs. Consequently, we were unable to assess the time elapsed between the last viral infection and the time of blood sampling. Secondly, some personal factors, like genetic factors which could interact with personal factors, were not considered in this analysis, and should deserve further investigation but are out of the scope of the present study. Furthermore, the large majority of our population is Caucasian, and generalization of our results to other ethnic groups cannot be done, but allows analyzing a homogenous population, therefore limiting risk for confounding bias. Additionally, one has to consider that a percentage of subjects (≥ 55%) had an allergic sensitization. Finally, given the EGEA study design, asthma could be considered as a collider bias and may distort the association investigated (40). However, the fact that all the patterns of associations reported in this study were stable regardless of the asthma status supports the absence of collider bias in our results.