Background and objectives: A new pandemic has emerged across the world:Covid-19. Covid-19 has affected hundreds of millions of people globally. To stop the spread of the virus and gain a mass immunity several vaccines have been developed. BNT162b2-mRNA-vaccine has been shown to be largely effective and is widely administered. However the vaccine is not free from adverse events that could discourage vaccination in many people. The aim was evaluated adverse effect and immunological effect after second dose of BNT162b2-mRNA-vaccine in a healthcare population that take Pidotimod versus control subjects. Methods: All nurses and doctors working in Covid-19 unit were proposed to participate, up to the enrollment of 30participants. 10 participants took Pidotimod 800mg bid orally fasting, from the fourth day before the second dose of the BNT162b2-mRNA-vaccine, for a total of six days. The remaining 20 participants did not take any therapy. We studied the differences in anti-SARS-CoV2 IgM and IgG levels and the difference of frequency of adverse events between the two groups Results: Although there was no significant difference in IgG production between the two groups, we found a lower frequency of vaccine adverse events in the group supplemented with pidotimod. Conclusions: This work demonstrates how pidotimod, despite not having a proven efficacy in increasing the production of antibodies, significantly reduces the adverse events described compared to people vaccinated without pidotimod supplementation. The results we described in this paper could encourage many more clinicians and people to vaccinate and gain the mass immunity needed to end this pandemic.