SARS-CoV-2 has caused the most devastating pandemic of all time in recent human history. However, there is a serious paucity of high-quality data on aggravating factors and mechanisms of co-infection. This study aimed to identify the trending patterns of bacterial co-infections and types and associated outcomes in three phases of the pandemic. Using quality hospital data, we have investigated the SARS-CoV-2 fatality rates, profiles, and types of bacterial co-infections before, during, and after COVID-19 vaccination. Out of 389 isolates used in different aspects, 298 were examined before and during the pandemic ( = 149 before, = 149 during). In this group, death rates were 32% during compared to only 7.4% before the pandemic with significant association (-value = 0.000000075). However, the death rate was 34% in co-infected ( = 170) compared to non-co-infected patients ( = 128), indicating a highly significant value (-value = 0.00000000000088). However, analysis of patients without other serious respiratory problems ( = 28) indicated that among the remaining 270 patients, death occurred in 30% of co-infected patients ( = 150) and only 0.8% of non-co-infected ( = 120) with a high significant -value = 0.00000000076. The trending patterns of co-infections before, during, and after vaccination showed a significant decline in with concomitant peaks in Gram negatives = 149 before/ = 149 during, including = 11/49 before/during, = 10/24, = 8/25, = 5/16, and 13/1. Nevertheless, in the post-vaccination phase ( = 91), gender-specific co-infections were examined for potential differences in susceptibility. Methicillin-resistant dominated both genders followed by in males and females, with the latter gender showing higher rates of isolations in both species. declined to third place in male patients. The drastic decline in and Gram negatives post-vaccination strongly implied a potential co-protection in vaccines. Future analysis would gain more insights into molecular mimicry.