Protection of natural infection against reinfection with SARS-CoV-2 JN.1 variant

This study investigated the effectiveness of natural infection in preventing reinfection with the JN.1 variant during a large JN.1 wave in Qatar, using a test-negative case-control study design. The overall effectiveness of previous infection in preventing reinfection with JN.1 was estimated at only 1.8% (95% CI: -9.3-12.6%). This effectiveness demonstrated a rapid decline over time since the previous infection, decreasing from 82.4% (95% CI: 40.9-94.7%) within 3 to less than 6 months after the previous infection to 50.9% (95% CI: -11.8-78.7%) in the subsequent 3 months, and further dropping to 18.3% (95% CI: -34.6-56.3%) in the subsequent 3 months. Ultimately, it reached a negligible level after one year. The findings show that the protection of natural infection against reinfection with JN.1 is strong only among those who were infected within the last 6 months, with variants such as XBB*. However, this protection wanes rapidly and is entirely lost one year after the previous infection. The findings support considerable immune evasion by JN.1. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors are grateful for support from the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core at Weill Cornell Medicine in Qatar; the Qatar Ministry of Public Health; Hamad Medical Corporation; and Sidra Medicine. The authors are also grateful for the Qatar Genome Programme and Qatar University Biomedical Research Center for institutional support for the reagents needed for the viral genome sequencing. ### 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 institutional review boards at Hamad Medical Corporation and Weill Cornell Medicine in Qatar approved this retrospective study with a waiver of 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I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The dataset of this study is a property of the Qatar Ministry of Public Health that was provided to the researchers through a restricted access agreement that prevents sharing the dataset with a third party or publicly. Future access to this dataset can be considered through a direct application for data access to Her Excellency the Minister of Public Health (https://www.moph.gov.qa/english/Pages/default.aspx). Aggregate data are available within the manuscript and its Supplementary information.