In COVID-19 convalescents, IgM, similarly to IgG1, preferentially targets the S1 domain of the Spike protein [78], the region that contains the RBD and N-terminus domains and the target of most neutralising antibodies and regions of high interest for developing passive immunotherapies to deal with new SARS-CoV-2 variants of concern [79]. This evidence concerns the gene CD40LG and COVID-19.