Background: To break the spread of COVID-19, people must adopt preven-tive health measures such as vaccination. A vaccine breakthrough infection is the detection of SARS-CoV-2 RNA or antigen in a specimen collected from a person ≥ 14 days after receipt of all recommended vaccine doses. Kwekwe City experienced an increase in breakthrough cases from one case (12 June 2021) to 39 cases (7 July 2021). The study was conducted to determine factors associated with breakthrough infections. Methods: We conducted an un-matched 1:2 case-control study. A case is defined as a patient who had two doses of a COVID-19 vaccine and had a positive SARS-CoV-2 antigen/PCR test at least two weeks after the date of receiving the second dose of the vac-cine in Kwekwe City from June 12, 2021. An interviewer-administered ques-tionnaire was used to collect data. We used the Epi Info software to generate means, frequencies, and proportions, to calculate measures of associations that include odds ratios. Results: Fifty-four cases in the records met the case definition for breakthrough infections, and two had died giving a case fatality rate of 3.7%. Fifty-one of the remaining 52 cases and 102 controls were re-cruited. Being within the age of 55 - 64 years (aOR = 12.22; 95% CI (1.15 - 129.81) and being unemployed (aOR = 0.26; 95% CI (0.07 - 0.93) were the independent factors associated with breakthrough infection. The median dura-tion in days between getting the second dose of the vaccine and getting tested was 57.0 (Q1 = 33; Q3 = 81) and 46 (Q1 = 33; Q3 = 64) for cases and controls respectively. There were significant differences in overall knowledge, controls had good knowledge compared to cases (p = 0.01). Conclusion: Individuals who were within the 55 - 64 years age group were more likely to have break-through infections. Those who had breakthrough infections had overall poor knowledge of COVID-19. Non-pharmacological interventions such as mask-wearing, social distancing, and frequent hand washing protect against having breakthrough infections. We recommended that residents get continu-ous education on the transmission, control, and prevention of the SARS-CoV-2 virus. The elderly should get booster doses of the vaccine.
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