ABSTRACT
Background: Although high vaccine effectiveness of messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines was reported in studies in several countries, data is limited from Asian countries, especially against the Delta (B.1.617.2) variant. Methods: We conducted a multicenter test-negative case-control study in patients aged [≥]16 visiting hospitals or clinics with signs or symptoms consistent with COVID-19 from July 1 to September 30, 2021, when the Delta variant was dominant ([≥]90% of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infections) nationwide in Japan. Vaccine effectiveness of BNT162b2 or mRNA-1273 against symptomatic SARS-CoV-2 infections was evaluated. Waning immunity among patients aged 16 to 64 was also assessed. Results: We enrolled 1936 patients, including 396 test-positive cases and 1540 test-negative controls for SARS-CoV-2. The median age was 49 years, 53.4% were male, and 34.0% had underlying medical conditions. Full vaccination (receiving two doses [≥]14 days before symptom onset) was received by 6.6% of cases and 38.8% of controls. Vaccine effectiveness of full vaccination against symptomatic SARS-CoV-2 infections was 88.7% (95% confidence interval [CI], 78.8 to 93.9) among patients aged 16 to 64 and 90.3% (95% CI, 73.6 to 96.4) among patients aged [≥]65. Among patients aged 16 to 64, vaccine effectiveness within one to three months after full vaccination was 91.8% (95% CI, 80.3 to 96.6), and was 86.4% (95% CI, 56.9 to 95.7) within four to six months. Conclusions: mRNA COVID-19 vaccines had high effectiveness against symptomatic SARS-CoV-2 infections in Japan during July 1 to September 30, 2021, when the Delta variant was dominant nationwide.