Based on the first immunological model of COVID-19 supported by an in-depth scientific report published on May 2nd of 2020 in the Journal of Pediatric Allergy and Immunology (Matricardi et al., 2020), the risk and severity of COVID-19 symptoms and potential fatality in healthy populations derives from the balance between two core parameters: (1) their overall level of viral exposure and (2) the efficacy of the local innate immune response (i.e., natural IgA and IgM antibodies, mannose-binding lectin) (Matricardi et al., 2020). This evidence concerns the gene CD40LG and COVID-19.