Using intelligent computer programs, the secondary structure and thermodynamic properties of hsa-mir-181a ACE2 were investigated in both vaccinated and unvaccinated samples, comparing them to the wild type. By utilizing the RNAalifold web server, a consensus structure of aligned micro-RNA sequences was predicted, along with the minimum free energy (MFE) and equilibrium base-pairing probabilities. The results showed a strong correlation between the secondary structure of hsa-mir-181a ACE2 and the vaccination status, with a higher MFE observed in the vaccinated group. This study proved a significant relationship between the secondary structure of hsa-mir-181a ACE2 and the selected class of vaccinated or unvaccinated. The value of (MFE) of the secondary structure of microRNA increased in vaccinated compared with unvaccinated, with a significant difference evident. Also, at the thermodynamic free energy (value) level, the vaccination was increased compared to the unvaccinated as the difference was clear and the relationship was achieved.