To assess SARS-CoV-2 reinfection incidence in the post-vaccination period, we carried out a prospective cohort study of blood donors from Amazonas and Sao Paulo States, Brazil. Anti-nucleocapsid immunoglobulin (IgG anti-N) tests carried out by blood centers in 2020 were used to identify previous SARS-CoV-2 infections in blood donors and divide them into two groups: prior infection (n=386) and no prior infection (n=111). From March 2021 to January 2022, donors were followed up for six months, during which IgG anti-N and real-time reverse transcription polymerase chain reaction tests were performed every two months to detect SARS-CoV-2 infections. Symptoms and vaccination status were also recorded. Most participants (93.6%) received at least one COVID-19 vaccine dose. Reinfection incidence in the prior infection group equaled 1.39 per 100 person-months (95% CI: 0.90-2.06), in comparison to 2.68 per 100 person-months (95% CI: 1.28-4.93) for new infections in those without prior infection. The incidence risk ratio showed no significant association (0.52, 95% CI: 0.25-1.13). However, prior infection significantly increased the probability of remaining uninfected (Log-rank: p=0.009). Most reinfections (84%) showed no symptoms and occurred post-vaccination during the Delta and Omicron waves. IgG anti-N seroprevalence decreased in the prior infection group (from 35.5% at baseline to 22.5% after six months, p=0.003). Despite no significant incidence risk ratio differences, donors with prior infection had lower infection rates and a higher likelihood of remaining uninfected. Persistent post-vaccination asymptomatic infections emphasize the need for ongoing prevention, genomic surveillance, and booster programs to address emerging variants and protect vulnerable populations.
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