Effectiveness and duration of a second COVID-19 vaccine booster

Using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluated the effectiveness against COVID-19 related ICU admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series plus a homologous booster, and CoronaVac primary series plus an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimated the vaccine effectiveness weekly from February 14 to August 15, 2022, by estimating hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot was 88.2% (95%CI, 86.2-89.9) and 90.5% (95%CI 89.4-91.4) against ICU admissions and death, respectively. Vaccine effectiveness showed a mild decrease for all regimens and outcomes, probably associated with the introduction of BA.4 and BA.5 Omicron sub-lineages and immunity waning. The duration of effectiveness suggests that no additional boosters are needed six months following a second booster shot. ### Competing Interest Statement R. Araos has received consulting fees from AstraZeneca. R. Araos and A. Jara have received consulting fees from Pfizer and research support from Sinovac. This support is not related to this article. The remaining authors have no conflicts of interest to declare. ### Funding Statement This research was supported by the Agencia Nacional de Investigacion y Desarrollo (ANID) through the Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) grant N1220907 to AJ; Advanced Center for Chronic Diseases (ACCDiS) ANID FONDAP grant N15130011 to RA; and Research Center for Integrated Disaster Risk Management (CIGIDEN) ANID FONDAP grant N15110017 to EU. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Comite Etico Cientifico (Ethics committee/IRB) Clinica Alemana Universidad del Desarrollo, Santiago, Chile, gave ethical approval for this research. The study was considered exempt from informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Owing to data privacy regulations in Chile, this study's individual-level data cannot be shared (Law 19.628). Aggregate data on vaccination, including demographics, and COVID-19 incidence, are publicly available at .