Only recently, the investigations have been suggesting that the achievement of a longitudinal protective immunity in COVID-19 convalescents and vaccinated subjects, as well as the development of long-term protection upon re-exposure to this pathogen both in the single individual and in the general population, depends on a coordinated, specific and polyclonal immune response, mediated by CD4/CD8 T- and B-lymphocytes, toward a wide spectrum of different epitopes belonging to distinct SARS-CoV-2 proteins [51]. This evidence concerns the gene CD4 and COVID-19.