key: cord-0941662-ra83ehv9 authors: Yan, Yan; Naito, Toshio; Tabe, Yoko; Ito, Kanami; Nojiri, Shuko; Deshpande, Gautam A.; Seyama, Kuniaki; Takahashi, Kazuhisa title: Increased Delta variant SARS-CoV-2 infections in a highly vaccinated medical center in Japan date: 2022-04-12 journal: Vaccine DOI: 10.1016/j.vaccine.2022.04.029 sha: 4a81f704edbc77c798da75002baae3e9ff63c322 doc_id: 941662 cord_uid: ra83ehv9 The Delta variant has dominated SARS-CoV-2 infections in Tokyo, Japan from June 2021 to date. We conducted a retrospective cohort study to assess BNT162b2 vaccine effectiveness during the surge in Delta among 3,911 healthcare workers (HCWs) at a medical center of Tokyo with a high vaccination rate of 84.1%. With strict infection control protocols including universal masking, only a small number of cases among vaccinated and unvaccinated HCWs were identified before June. As Delta spread in Tokyo, 16 cases among 3,289 fully vaccinated HCWs and 11 cases among 574 unvaccinated HCWs were reported in July and August (case rate in August: 4.0 vs. 19.2 per 1,000). All breakthrough cases were confirmed as Delta. While our study confirms a robust vaccine effectiveness of BNT162b2 vaccine against Delta, rising breakthrough cases suggest that continued infection control measures are warranted in higher risk environments, even when high rates of vaccination coverage are achieved. The Delta variant has dominated SARS-CoV-2 infections in Tokyo, Japan from June 2021 to date. We conducted a retrospective cohort study to assess BNT162b2 vaccine effectiveness during the surge in Delta Previous studies have shown the Delta variant has increased transmissibility even in some fully vaccinated individuals. 7, 8 Resurgence of SARS-CoV-2 infections has also been reported in medical centers with high rates of vaccination. 9 However, reports addressing Delta's impacts on breakthrough infections among fully vaccinated individuals mainly come from North America and Europe, where the social dynamics of compliance with public health measures may differ from other parts of the world. Moreover, effectiveness of mRNA vaccines in ethnic groups of the Western Pacific region may also differ compared to populations in North America and Europe, as suggested by our recent report of increased reactogenicity among Japanese HCWs receiving BNT162b2 vaccines. 10 To explore these potential differences, we conducted a retrospective cohort study to assess BNT162b2 vaccine effectiveness during the Delta surge among HCWs at a tertiary level center with a high vaccination rate in Tokyo, Japan. Regarding infection control protocols, masks are mandated for employees at all times except while eating. Outside of work hours, dining with more than two non-family members is strongly discouraged. Temperature is checked and self-reported daily by all employees; those with temperature above 37.5 o C are required to submit a PCR test for further examination. Additional The primary outcome of this study was case rate (attack rate) among fully vaccinated versus unvaccinated HCWs. In addition, detailed data on variant type, along with duration between full vaccination to infection and vaccine-induced anti-S IgG levels, were analyzed to more thoroughly assess the impacts of the Delta variant and efficacy of vaccination. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 27 (IBM Japan). In addition, the bootstrap method (1000 replications) was used to produce the confidence interval (CI) for the case rate of infection. The CI is based on normal-theory, assuming that log(case rate) is normally distributed. This study was approved by Juntendo University Institutional Review Board (No. Table 2) . Regarding infections in unvaccinated HCWs, except for one case with N501Y mutation, all cases with available nasopharyngeal or saliva samples were identified as having L452R mutation. (Figure 1-2 and 1-3) The prevalence of Delta variant in JUH is shown in Figure 2 and was consistent with that of the Tokyo metropolitan area. Among all reported positive tests, including PCR tests for non-employees such as inpatients before admission, the Delta variant comprised 88.9% of all cases, increasing to 98.0% after exclusion of cases in which nasopharyngeal or saliva samples were unavailable. With strict infection control protocols such as universal masking and actively encouraging employees to minimize social events, few infections among HCWs were reported before June when the wild-type, Alpha, and other variants dominated the Tokyo Metropolitan area. In contrast, with the rapid spread of the Delta variant beginning in mid-June, several infections occurred throughout July and August, even among fully vaccinated individuals. A previous retrospective cohort study in Singapore reported lower Ct values and longer viral shedding associated with the Delta variant, suggesting increased transmissibility. 8 Although the correlation between Ct values and the amount of virus per specimen is imperfect, our study showed relatively low Ct values associated with the Delta variant among the vaccinated HCWs, supporting the findings of the Singapore study. 8, 15 The breakthrough cases found in our study received two doses of the BNT162b2 vaccine in March and April, with an average of less than four months between full vaccination and infection, shorter than the six month period currently being considered for booster vaccines. 16 Marginally diminished vaccine effectiveness against Delta has been reported in several previous studies, and is corroborated in our population. 17, 18 The breakthrough cases found in our highly vaccinated medical center are likely to be the result of a combination of marginally lower vaccine effectiveness against Delta and increased transmissibility of the variant. However, even during Delta spread, our overall breakthrough case numbers remained low. Strict infection control protocols including universal masking were continued even after implementation of our vaccination program. Effectiveness of face masks in preventing airborne transmission and reducing SARS-CoV-2 cases has been shown in multiple previous studies, and many governmental and professional organizations continue to recommend indoor mask-wearing to prevent COVID-19 infections during Delta spread. 19, 20 Strict universal masking has likely contributed to overall lower surge numbers in the Japanese setting. There are several limitations to our study worth addressing. First, although PCR testing is performed for those reporting temperature above 37.5 o C during daily checks, close contacts of confirmed cases, and/or those having flu-like symptoms, asymptomatic cases may be missed; therefore, actual case rate are likely underestimated in our results. Second, due to overall low case rates in this hospital, prior infections among all healthcare workers not infected during the studied period were not analyzed in this study. However, all studied breakthrough cases were checked and found not to have prior infections. Lack of analysis on acquired immunity via prior infections among all healthcare workers might have underestimated the vaccine effectiveness. Third, although the strict infection control measures implemented in this tertiary level hospital may represent the general compliance of Japanese citizens at large, the level of control in the healthcare workplace setting is likely higher than average; our findings are particularly applicable to highrisk healthcare environments and extrapolation to the general population should be interpreted with caution. Our retrospective cohort study provides real-world evidence of maintained robust BNT162b2 vaccine effectiveness against Delta in an Asian population, yet also revealed increased breakthrough cases in this highly vaccinated medical center. With demand for vaccinations in Japan continuing at a strong pace, all individuals willing to receive COVID-19 vaccines are expected to be fully vaccinated by the end of November 2021; rapid vaccination programs are expected in other countries of the Western Pacific region in the coming months as well. Nonetheless, our findings emphasize the need for ongoing vigilance toward breakthrough infections despite an environment with high vaccination coverage and strict public health protocols. From a public health policy perspective, given the current prevalence of the Delta variant and the possible future emergence of highly transmissible variants, our data suggest that infection control measures such as masking, personal hygiene, and social distancing will continue to be required in high-risk settings. Prof Naito had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of data analysis. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Yan, Deshpande, Naito. Fully vaccinated workers 0 0 0 0 3 13 Partially vaccinated workers 0 1 0 0 0 0 Unvaccinated workers 0 2 Ministry of Health, Labour and Welfare Bureau of social welfare and public health SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. 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Guide for Field Operations High-yield RNA-extraction method for saliva Centers for Disease Control and Prevention. Research Use Only 2019-Novel Coronavirus (2019-nCoV) Real-time RT-PCR Primers and Probes 16 Centers of Disease Control and Prevention. Who Is Eligible for a COVID-19 Vaccine Booster Shot? Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variants prevalence Vaccine effectiveness against infection with the 2) variant, Norway Effectiveness of face masks in preventing airborne transmission of SARS-CoV-2. mSphere Face masks considerably reduce COVID-19 cases in Germany Statistical analysis: Ito, Tabe, Nojiri, Seyama.Administrative, technical, or material support: Tabe, Seyama, Takahashi.Supervision: Naito, Takahashi.All authors meet the ICMJE authorship criteria. The authors declare no conflict of interest. We thank healthcare workers in Juntendo University Hospital, Tokyo, Japan for their participation. Supervision: Naito, Takahashi.All authors meet the ICMJE authorship criteria. The authors declare no conflict of interest. None.