Effectiveness of Messenger RNA Coronavirus Disease 2019 Vaccines Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Delta Variant Epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS).

Background: Although high vaccine effectiveness of messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines has been reported in studies in several countries, data are 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 years visiting hospitals or clinics with signs or symptoms consistent with COVID-19 from 1 July to 30 September 2021, when the Delta variant was dominant (≥90% of 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 16-64 years 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 2 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%-93.9%) among patients aged 16-64 years and 90.3% (95% CI, 73.6%-96.4%) among patients aged ≥65 years. Among patients aged 16-64 years, vaccine effectiveness was 91.8% (95% CI, 80.3%-96.6%) within 1-3 months after full vaccination, and 86.4% (95% CI, 56.9%-95.7%) within 4-6 months.

Conclusions: mRNA COVID-19 vaccines had high effectiveness against symptomatic SARS-CoV-2 infections in Japan during July-September 2021, when the Delta variant was dominant nationwide.