On June 4, 2021, Italy launched the COVID-19 vaccination of adolescents to pace down the COVID-19 spread. Although clinical trials have evaluated mRNA vaccine effectiveness in adolescents, there is limited literature on its real-world effectiveness. Accordingly, this study aimed to estimate the effectiveness of mRNA COVID-19 vaccines against SARS-CoV-2 infection and mild or severe COVID-19 in a cohort of Sicilian adolescents within a six-month observation period.


A retrospective cohort study was conducted with adolescents aged 12–18, residents of Sicily, that were followed from July 15 to December 31, 2021. SARS-CoV-2 infections, mild and severe COVID-19, and COVID-19-related intubation or deaths during the study period were compared between subjects vaccinated with two doses of mRNA vaccines and unvaccinated individuals. The Cox regression analysis, adjusted for age and sex, was performed to compare the two groups.


Overall, the study included a total at-risk population of 274,782 adolescents with 61.4% (168,633) of them having completed the vaccination cycle by the end of the study. Unvaccinated subjects had higher incidence rates of SARS-CoV-2 (1,043 x 10,000 vs. 158.7 x 10,000 subjects), mild COVID-19 (27.7 x 10,000 vs. 1.8 x 10,000 subjects) and severe COVID-19 (1.41 x 10,000 vs. 0 subjects) compared to the vaccinated population. The estimated adjusted vaccine effectiveness against SARS-CoV-2 infection was 71.2%, reaching 92.1% and 97.9% against mild and severe COVID-19, respectively.


This study provides rigorous evidence of the mRNA COVID-19 vaccines effectiveness in protecting adolescents from both SARS-CoV-2 infection, and mild or severe COVID-19.

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Competing Interests

CONFLICT OF INTEREST DISCLOSURES: The authors have no conflicts of interest relevant to this article to disclose.