Effectiveness of 2024/25 KP.2 vaccine against outpatient COVID-19 in Canada

Abstract Between November 2024 and April 2025, the Canadian Sentinel Practitioner Surveillance Network assessed KP.2 vaccine effectiveness against outpatient COVID-19 by test-negative design. Vaccination protected best during the first two months, reducing risk by two-thirds among vaccinated versus unvaccinated individuals, declining by 3-4 months, and reducing the risk overall by half. Competing Interest Statement DMS is Principal Investigator on grants received to her institution from the Public Health Agency of Canada in support of this work. She has received grants from Pacific Public Health Foundation and Canadian Institutes of Health Research for unrelated work, also paid to her institution. SC reports funding from the Public Health Agency of Canada paid to her institution, but not pertaining to the current study. Other authors have no conflicts of interest to declare. Funding Statement This work was supported by funding provided by the BC Ministry of Health, Public Health Ontario, the Ministè;re de la santé et des services sociaux du Québec and the Public Health Agency of Canada (arrangement number 2324-HQ-000038). 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: In British Columbia, Ontario, and Québec, waiver of ethics review was provided. In British Columbia both the University of British Columbia Clinical and Behavioural Research Ethics Board (REB)s waived review because such evaluations are considered within the core public health mandate of the BC Centre for Disease Control (BCCDC). In Ontario, the Public Health Ontario Ethics Review Board also determined the project did not require ongoing review as the activities are considered routine public health practice in fulfilment of Public Health Ontario's legislated mandate, and not research. In Quebec, such evaluations are similarly considered part of core public health surveillance for which reason the Centre Hospitalier Universitaire de Québec REB also provided separate waiver of review. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data for SPSN SARS-CoV-2 viruses meeting provincial and/or national criteria for upload and their submitting and contributing laboratories can be found on GISAID using the Epi_Set_ID: EPI_SET_250903wr.