Vaccine effectiveness against SARS-CoV-2 variants in adolescents from 15 to 90 days after second dose: a population-based test-negative case-control study

To estimate the vaccine effectiveness (VE) against hospitalization and severe illness in adolescents due to infection with SARS-CoV-2 variants (gamma, delta, and omicron).A test-negative, case-control analysis was conducted in Brazil from July 2021 to March 2022. We enrolled 8,458 eligible individuals (12 - 19 years of age) hospitalized with an acute respiratory syndrome, including 3,075 cases with laboratory-proven COVID-19 and 4,753 controls with negative tests for COVID-19. The primary exposure of interest was vaccination status. The primary outcome was SARS-CoV-2 infection during gamma/delta vs. omicron-predominant periods. The adjusted odds ratio for the association of prior vaccination and outcomes was used to estimate VE.In the pre-omicron period, VE against COVID-19 hospitalization was 88% (95%CI, 83% to 92%) and has dropped to 59% (95%CI, 49% to 66%) during the omicron period. For hospitalized cases of COVID-19, considering the entire period of the analysis, 2-dose schedule was moderately effective against ICU admission (46%, [95%CI, 27 to 60]), need of mechanical ventilation (49%, [95%CI, 32 to 70]), severe COVID-19 (42%, [95%CI, 17 to 60]), and death (46%, [95%CI, 8 to 67]). There was a substantial reduction of about 40% in the VE against all endpoints, except for death, during the omicron-predominant period. Among cases, 240 (6.6%) adolescents died; of fatal cases, 224 (93.3%) were not fully vaccinated.Among adolescents, the VE against all endpoints was substantially reduced during the omicron-predominant period. Our findings suggest that the two-dose regimen may be insufficient for SARS-CoV-2 variants and support the need for updated vaccines to provide better protection against severe COVID-19.