AbstractMembrane computing is a natural computing procedure inspired in the compartmental structure of living cells. This approach allows mimicking the complex structure of biological processes, and, when applied to transmissible diseases, can simulate a virtual ‘epidemic’ based on interactions between elements within the computational model according to established conditions. General and focused vaccination strategies for controlling SARS-Cov-2 epidemics have been simulated for 2.3 years from the emergence of the epidemic in a hypothetical town of 10320 inhabitants in a country with mean European demographics where COVID-19 is imported. The age and immunological-response groups of the hosts and their lifestyles were minutely examined. The duration of natural, acquired immunity influenced the results; the shorter the duration, the more endemic the process, resulting in higher mortality, particularly among elderly individuals. During epidemic valleys between waves, the proportion of infected patients belonging to symptomatic groups (mostly elderly) increased in the total population, a population that largely benefits from standard double vaccination, particularly with boosters. There was no clear difference when comparing booster shots provided at 4 or 6 months after standard double-dose vaccination. Vaccines even of moderate efficacy (short-term protection) were effective in decreasing the number of symptomatic cases. Generalized vaccination of the entire population (all ages) added little benefit to overall mortality rates, and this situation also applied for generalized lockdowns. Elderly-only vaccination and lockdowns, even without general interventions directed to reduce population transmission, is sufficient for dramatically reducing mortality.