This might be related to low assay specificity due to the polymeric nature of IgM, as cross-reactive anti-SARS-CoV-2 IgM antibodies were also detected in pre-COVID-19 samples.33 Furthermore, these prevaccination IgM responses could be related to the cross-reactivity induced against other human CoVs following infection due to isotype class-switching. This evidence concerns the gene CD40LG and infection.