To estimate the relative, short-term effectiveness of NVX-CoV2373 versus BNT162b2 (Pfizer– BioNTech) in preventing SARS-CoV-2 infection and severe COVID-19 disease during the Omicron variant dominance in South Korea. Retrospective cohort-study among ≥12-year-olds using the K-COV-N database, which links COVID-19 vaccine registry data with health insurance claims data. The Cox proportional-hazards model and inverse probability of treatment weighting were employed to calculate adjusted hazard ratios (aHRs). Among homologous primary-series NVX-CoV2373 versus BNT162b2 recipients, the aHR was 0.86 (95% CI: 0.82–0.91) for all laboratory-confirmed and 0.80 (95% CI: 0.48–1.33) for severe infections. Among homologous 1st-booster recipients, it was 0.74 (95% CI: 0.61–0.90) for all laboratory-confirmed and 0.48 (95% CI: 0.12–1.92) for severe infections. At 30-days post-immunization, we observed homologous, NVX-CoV2373 primary-series and 1st-booster offered added protection against SARS-CoV-2 infection versus BNT162b2; while there was numerically lower risk of severe disease among NVX-CoV2373-vaccinated, no statistically significant differences were observed.

EG, EB, YJC, and SAC are investigators of the study and do not have any conflicts to report. JF, MR, and MV are all employees of Novavax, Inc. and may hold stock in Novavax, Inc. CB used to be employed by Novavax, Inc., and holds stock in Novavax, Inc.

This work was supported by Novavax, Inc. The sponsor had primary responsibility for study design, protocol development, study monitoring, data management, and statistical analyses. All authors reviewed and approved the manuscript before submission.

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:

This study was approved by the Korea University Institutional Review Board (IRB No. 2023AN0124).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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

The authors do not have permission to share data.