First cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the Dominican Republic (DR) were reported in early 2020. During the first trimester of 2021 a national vaccination campaign was deployed, including whole-virus inactivated, adenovirus-based, and mRNA vaccines platforms. To better understand the effectiveness and efficiency of vaccines to reduce COVID-19 related deaths, among vaccinated (2-doses), unvaccinated and partially vaccinated (1-doses), and SARS-CoV-2 variants we analyzed clinical and molecular data obtained from breakthrough infections in hospitalized individuals. Samples from SARS-CoV-2 infected hospitalized patients were collected for viral sequencing. During the study period, we analyzed the data of thirty-three (n=33) COVID-19 case-patients from June to September 2021. Studied cases reported receiving a whole-virus attenuated vaccine (CoronaVac) in 36.8%. The survival rate among two-dose vaccinated individuals was 73% (95% CI, 70.8 to 74.2) compared to 65% in unvaccinated individuals. Molecular variant analysis of variant circulation among infections was initially due to B.1.621 (Mu) and rapidly shifting to B.1.617 (Delta) variants. No differences in outcomes between Mu, Iota, or Delta infections were observed. This suggests that VOIs can also have a deleterious impact on vaccinated individuals.