key: cord-0937315-tf6brdvl authors: Maeda, Haruka; Saito, Nobuo; Igarashi, Ataru; Ishida, Masayuki; Suami, Kazuya; Yagiuchi, Ai; Kimura, Yuya; Komino, Masaru; Arai, Hiromi; Morikawa, Toru; Motohashi, Iori; Miyazawa, Rei; Moriyama, Tetsu; Kamura, Hiroshi; Terada, Mayumi; Kuwamitsu, Osamu; Hayakawa, Tomoichiro; Sando, Eiichiro; Ohara, Yasuji; Teshigahara, Osamu; Suzuki, Motoi; Morimoto, Konosuke title: Effectiveness of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections during the Delta variant epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS) date: 2022-04-19 journal: Clin Infect Dis DOI: 10.1093/cid/ciac292 sha: a68d64cffce235809d5babff8ddcb1f79a3a1a5b doc_id: 937315 cord_uid: tf6brdvl 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], 78.8–93.9) among patients aged 16 to 64 and 90.3% (95% CI, 73.6–96.4) 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, 80.3–96.6), and was 86.4% (95% CI, 56.9–95.7) 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. vaccines, especially against the Delta (B.1.617.2) variant, from Asian countries is limited. 8 In February 2021, the Japanese government initiated a national COVID-19 vaccination 9 campaign (Supplementary Figure 1) . It is crucial to assess COVID-19 vaccine effectiveness 10 domestically when evaluating the national policy and, going forward, determining the optimal 11 vaccination policy. Vaccine effectiveness has been estimated to attenuate due to the emergence of 12 new variants [7] . Accordingly, we started surveillance activity from July 1, 2021 to monitor 13 vaccine effectiveness of COVID-19 vaccines in Japan, named Vaccine Effectiveness Real-time 14 Surveillance for SARS-CoV-2 (VERSUS). In this study, we evaluated vaccine effectiveness of 15 mRNA COVID-19 vaccines, BNT165b2 and mRNA-1273, against symptomatic SARS-CoV-2 16 infections during the Delta variant epidemic in Japan using data registered for our surveillance. We conducted a prospective test-negative case-control study [8, 9] . The case group included 4 individuals having signs or symptoms and positive test results of SARS-CoV-2, and the control 5 group included individuals having signs or symptoms but negative test results of SARS-CoV-2. 6 All SARS-CoV-2 tests were performed in medical institutions in clinical practice. The following 7 test methods were included, which are commonly used for diagnosis in Japan [10, 11]: nucleic 8 acid amplification tests including polymerase chain reaction (PCR), loop-medical isothermal 9 amplification (LAMP) [12] , nicking endonuclease amplification reaction (NEAR) [13] , and 10 transcription-mediated amplification (TMA) [14] ; and antigen quantification test [15, 16] . A 11 rapid antigen test was not included in this study. Statistical analysis 9 The odds ratio (OR) was calculated by comparing the odds of antecedent COVID-19 vaccination 10 in test-positive versus test-negative patients. A mixed-effects logistic regression model was used 11 to calculate adjusted ORs. Age, sex, presence of underlying medical conditions, calendar weeks, 12 and history of contact with COVID-19 patients were applied as the fixed effects, and study sites 13 as the random effect to the logistic model. Vaccine effectiveness was defined as one minus 14 adjusted ORs, expressed as a percentage [8, 9] . vaccines. We also performed analyses on each vaccine product separately. We excluded the 5 episodes with undocumented vaccine products from the analysis of each vaccine product. 6 Additionally, to assess the extent of waning immunity of mRNA COVID-19 vaccines against the 7 Delta variant in Japan, we evaluated vaccine effectiveness separately between two groups: 8 episodes within one to three months and episodes within four to six months after full vaccination 9 status (14 days after the second vaccine receipt) among patients aged 16 to 64 years. We also Table 8 1 and Supplementary Table 2 and are similar to the primary analysis. In this prospective test-negative case-control study, we confirmed high mRNA COVID-19 12 vaccine effectiveness against symptomatic SARS-CoV-2 infections in Japan. We estimated that against symptomatic SAR-CoV-2 infections in Japan. The patients included in this study were those examined for SARS-CoV-2 tests between 14 Vaccination is one of the essential strategies to tackle the COVID-19 pandemic, and it is crucial 15 to continue this surveillance activity, including the evaluation of vaccine effectiveness against the 16 Omicron variant, to assess the optimal domestic COVID-19 vaccination strategy. Efficacy and Safety of the mRNA-1273 SARS-2 CoV-2 Vaccine Safety and Efficacy of the BNT162b2 mRNA 4 Covid-19 Vaccine Safety and efficacy of the ChAdOx1 nCoV-6 19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised 7 controlled trials in Brazil, South Africa, and the UK. The Lancet BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting Vaccine effectiveness against 11 symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-12 MOVE-COVID-19 project Efficacy and effectiveness of COVID-19 15 vaccines against SARS-CoV-2 infection: interim results of a living systematic review Methods for the Detection of SARS-CoV-2 from Nasopharyngeal and Nasal Swabs from 1 Individuals Diagnosed with COVID-19 Ministry of Health, Laour and Welfare. Information on the approval of in vitro diagnostic 3 reagents (test kits) for SARS-CoV-2 Evaluation of Lumipulse(R) G SARS-CoV-2 antigen 7 assay automated test for detecting SARS-CoV-2 nucleocapsid protein nasopharyngeal swabs for community and population screening Prospective study of 1308 nasopharyngeal 11 swabs from 1033 patients using the LUMIPULSE SARS-CoV-2 antigen test: 12 Comparison with RT-qPCR Ministry of Health, Laour and Welfare. COVID-19 Vaccines