key: cord-1013174-xsxss6z2 authors: Yi, Seonju; June Choe, Young; Sang Lim, Do; Roen Lee, Hye; Kim, Jia; Kim, Yoo-Yeon; Kyung Kim, Ryu; Jung Jang, Eun; Lee, Sangwon; Park, Eunjoo; Kim, Seung-Jin; Park, Young-Joon title: Impact of National Covid-19 Vaccination Campaign, South Korea() date: 2022-05-08 journal: Vaccine DOI: 10.1016/j.vaccine.2022.05.002 sha: e5802823026255aae2a507709aab858bf0191a3a doc_id: 1013174 cord_uid: xsxss6z2 BACKGROUND: We evaluate the overall effectiveness of the nationwide vaccination campaign using ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines in preventing Covid-19 in South Korea. METHODS: The National Surveillance System with the National Immunization Registry were linked to form a large-linked database for assessment. Age-adjusted incidence of SARS-CoV-2 infection, severe disease, and death by vaccination status are calculated. Weekly vaccine effectiveness was calculated based on incidence rate ratio (IRR) between fully-vaccinated and unvaccinated persons, as: IRR = incidence rate of vaccinated / incidence rate of unvaccinated. We estimate the cumulative SARS-CoV-2 outcome overtime comparing the observed case with predicted cases without vaccination. RESULTS: Age-adjusted incidence in unvaccinated persons (5.69 per 100,000 person-day) was 2.7 times the rate in fully vaccinated (2.13 per 100,000 person-day) persons, resulting effectiveness against SARS-CoV-2 infection of 63%. Vaccine effectiveness against severe disease and death were 93% and 95%, respectively. Between March and October 2021, estimated Covid-19 related outcomes averted by vaccinations were: 46,508 infections, 3,424 severe diseases, and 718 deaths. CONCLUSIONS: We found significant protection for national Covid-19 vaccination campaign against Covid-19 severe disease, and death in target populations, but there was an unexpected decreased protection against SARS-CoV-2 infection, highlighting the importance of continued surveillance and assessment. Since the emergence of severe acute respiratory disease syndrome coronavirus-2 (SARS-CoV-2), coronavirus disease 2019 (Covid-19) has caused 248 million cases with over 5 million deaths globally, as of November 2021. [1] After widespread use of viral vectorbased and mRNA-based Covid-19 vaccines, the incidence, hospitalization, and death due to SARS-CoV-2 decreased noticeably in many countries and regions; however, little is known about the vaccine effectiveness in Asian countries. [2] Introduction of Covid-19 vaccines began in February 2021 in South Korea, with two viral vector-based vaccines (ChAdOx1 nCoV-19 and Ad26.COV2.S) and two mRNA-based vaccines (BNT162b2 and mRNA-1273) adopted by the Korean national vaccination campaign. Working in conjunction with the national immunization technical advisory group, Korean government instituted a targeted vaccination program delivered through vaccination centers and primary care. [3] Vaccinations were initially offered to high risk persons in longterm care facilities and healthcare professionals, which were expanded to all persons aged 12 years and above, by October 2021. [4] Over the course of the pandemic, all reverse transcription polymerase chain reaction (RT-PCR) confirmed Covid-19 cases were reported to the government, while all vaccinations were registered to the national immunization registry. [4, 5] By linking these two large databases, we aimed to evaluate the overall effectiveness of the national vaccination campaign among persons ≥18 years of age, in preventing SARS-CoV-2 infection, severe disease case, and Covid-19 related death in South Korea. In this study, we report the number of SARS-CoV-2 infections, Covid-19 severe disease cases, and Covid-19-related deaths; and estimate the cases averted via the direct effect of nationwide Covid-19 vaccination program, between March 13, 2021 (surveillance week 11) and October 2, 2021 (surveillance week 40), in all adults aged 18 years and older in Korea. The study assesses the incidence rates of SARS-CoV-2 infections and severe disease cases, and subsequent case fatality rates among all individuals who were vaccinated with at least one dose, with at least 14 days of follow-up. In Korea, SARS-CoV-2 RT-PCR testing had been widely available since the beginning of pandemic, which is mandated for close contacts of infected person, people with febrile or respiratory symptoms, or people coming from abroad. [4] All RT-PCR-confirmed SARS-CoV-2 infections, severe diseases, and deaths are reported to the government on daily basis. In the case who wishes to be tested regardless of above criteria, non-PCR based testing can be done, which then are reflexed to RT-PCR testing, hence are notified to the government. From January 2020 to February 2021, a total of 89,902 RT-PCR-confirmed SARS-CoV-2 cases were reported in Korea, out of 51 million residents. [4] The nationwide Covid-19 vaccination program was launched on February 26, 2021. Given the supply constrains with the vaccines in the earlier phase, the government had the complete control over the vaccine distribution in different target groups. Vaccines were administered in vaccination centers or outpatient clinics with no out-of-pocket costs. Initially in the February, the ChAdOx1 nCoV-19 vaccination was offered to the residents and workers at long-term care facilities (LTCFs), and the BNT162b2 to the healthcare professionals (HCPs) at Covid-19 designated hospitals (Supplementary Table 1 ). By June and July, Ad26.COV2.S and mRNA-1273 vaccines were introduced to different target population. Between the surveillance weeks 11 and 40, the vaccination coverage rate has increased in a stepwise manner, largely due to intermittent supply constraints of the vaccines (Supplementary Figure 1) . We linked the Covid-19 National Surveillance System with the National Immunization Registry to form a large-linked database (LLDB), comprising 172,049 PCR- We first compare the type of vaccine, age group, sex, health outcome (severe disease, death) for fully vaccinated, partially vaccinated, and unvaccinated persons. Age-adjusted incidence of SARS-CoV-2 infection, severe disease, and death by vaccination status are calculated. The rates were stratified by vaccination status and were calculated as ratio between the number of events and total observation period per 100,000 person-time in days. Weekly vaccine effectiveness was calculated based on incidence rate ratio (IRR) between fully-vaccinated and unvaccinated persons, as: IRR = incidence rate of vaccinated / incidence rate of unvaccinated. We then estimate the cumulative SARS-CoV-2 outcome overtime comparing the crude number of cases with predicted cases without vaccination. To estimate the weekly number of averted cases, we used the following formula: cases averted = weekly number of observed persons*vaccine coverage rate*(expected number of cases in unvaccinatedobserved number of cases in vaccinated); using direct standardization to adjust for difference in population structure between vaccinated and unvaccinated persons. Daily, age-adjusted incidence rates were calculated for vaccinated (fully + partially) persons and unvaccinated persons for three health outcomes. The person-days for vaccinated individuals for each day was estimated by multiplying the proportion of people who were at least partly vaccinated by population. The person-days for unvaccinated individuals for each day was determined by subtracting the number of person-days contributed by vaccinated persons from the total census population. This study was conducted as a legally mandated public health investigation under the authority of the Korean Infectious Diseases Control and Prevention Act (No. 12444 and No. 13392) and was not a research that was subject to institutional review board approval; therefore, written informed consent was not required. The number of vaccinations has increased from 20,878 (0.3% of target population) in Among all Korea residents, the age-adjusted incidence increased among unvaccinated, partially vaccinated, and fully vaccinated persons, with the highest rates among unvaccinated persons after week 28 ( Figure 1A) . By week 40, in unvaccinated persons, the age-adjusted incidence (5.69 per 100,000 person-day) was 1.9 times the rate in partially vaccinated (3.05 per 100,000 person-day) and 2.7 times the rate in fully vaccinated (2.13 per 100,000 person-day) persons, resulting vaccine effectiveness against SARS-CoV-2 infection of 63%. The age-adjusted incidence for severe disease and case fatality rate for partially and fully vaccinated persons remained relatively low compared to the rate for unvaccinated persons ( Figure 1B and 1C) . By week 40, the age-adjusted incidence for severe disease in Our findings suggest a high vaccine effectiveness for preventing serious disease and death from target population, however, as in studies from other countries, the vaccines may have reduced effectiveness in preventing SARS-CoV-2 infections. We report an Another U.K. study showed the reduced effectiveness of 10-13% for BNT162b2 and 16% for ChAdOx1 in preventing delta-related infections compared to alpha variant. [12] Since June 2021, the delta variant has emerged as the predominant strain in Korea, which may have affected the effectiveness in preventing SARS-CoV-2 infection, as shown in our study. [4, 13] The reduced effectiveness over time may be affected by waning immunity, or the secondary vaccine failure. In all age groups in Israel, immunity against delta variant waned in a few months after receipt of the second dose of vaccine. [14] A matched test-negative case-control study from Qatar showed that the variant-specific effectiveness waned in the same for BNT162b2, however, the protection against hospitalization and death persisted for 6 months. [15] A study from Israel reported a significantly lower incidence of booster-dose recipients compared with non-booster dose recipients, where delta variant was the predominant virus. [16] Since there has been emergence of delta variant affecting vaccine effectiveness against SARS-CoV-2 infection, these results may lead to public need for the booster doses in Korea. [17] Despite the reduced effectiveness against SARS-CoV-2 infection over time, our results suggest residual protection against severe disease and death in target population if they had been fully vaccinated. Our study demonstrates that the national vaccination campaign was instrumental to reducing the Covid-19 related severe disease and death. As postulated by previous modelling study, high vaccination coverage in conjunction with continued nonpharmaceutical intervention may be crucial in mitigating from Covid-19. [18] As the new variants may emerge among unvaccinated individuals, our findings underscore the public health need to accelerate vaccination coverage and close the vaccination coverage gaps. Our study has number of limitations. First, this is an observation study, in which neither vaccination or Covid-19 testing were made at random. It is plausible that the vaccination status may have affected chances of getting tested. Second, the difference in relevant characteristics between vaccinated and unvaccinated population were not controlled beyond sex and age group. Given the limited clinical and demographic data obtained through nationally-collected surveillance system, it was challenging to emulate the target trial to estimate vaccine effectiveness. Despite these limitations, our study included accurate immunization registry of 53 million people and more than 170,000 RT-PCR confirmed Covid-19 case, which allowed us to present a real-world data from a large scale. Prior to this study, there were limited opportunities to directly evaluate the public vaccination program against SARS-CoV-2 in a national scale. We have presented a weekly estimation of incidence rates over time to avoid overestimation of vaccine effectiveness. The data shows dose-response to the vaccination in terms of number of doses and window period on effectiveness against SARS-CoV-2 infection, severe disease, and death. Given the presence of validated, real-time, internet-based immunization registry, the completeness is high because all the supply and reimbursement process was controlled by the government. Lastly, the use of complete national database may overcome the selection bias that can be introduced by non-random missing data. In summary, we found significant protection for national Covid-19 vaccination campaign against SARS-CoV-2 severe disease, and death in target populations, but there was an unexpected finding of decreased protection against SARS-CoV-2 infection. This Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Geneva: World Health Organization Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: A narrative review. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases Developing a Framework for Pandemic COVID-19 Vaccine Allocation: a Modified Delphi Consensus Study in Korea Republic of Korea: Korea Diseaes Control and Prevention COVID-19: Identifying countries with indicators of success in responding to the outbreak Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data SARS-CoV-2 vaccine protection and deaths among US veterans during 2021 USA: a retrospective cohort study BNT162b2 and ChAdOx1 nCoV-19 Vaccine Effectiveness against Death from the Delta Variant. The New England journal of medicine BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the SARS-CoV-2 Delta variant in Qatar. Nature medicine Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. The New England journal of medicine Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK. Nature medicine How to deal with the Delta variant this fall. Osong public health and research perspectives Waning Immunity after the BNT162b2 Vaccine in Israel. The New England journal of medicine Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar. The New England journal of medicine Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel Covid-19: How is the UK's vaccine booster programme faring? Dynamics of the COVID-19 epidemic in the post-vaccination period in Korea: a rapid assessment We would like to thank the COVID-19 Vaccination Task Force and Division of National Immunization, Korea Disease Control and Prevention Agency for their dedication to provide public health services in mitigating COVID-19 pandemic. Additionally, we are grateful to the staff at the local health departments for their dedication. The opinions expressed by authors contributing to this journal do not necessarily reflect the opinions of the Korea Disease Control and Prevention Agency or the institutions with which the authors are affiliated. None exist. None.