Rapid spread of the SARS-CoV-2 Omicron XDR lineage derived from recombination between XBB and BA.2.86 subvariants circulating in Brazil in late 2023

Recombination plays a crucial role in the evolution of SARS-CoV-2. The Omicron XBB* recombinant lineages are a noteworthy example, as they have been the dominant SARS-CoV-2 variant worldwide in the first half of 2023. Since November 2023, a new recombinant lineage between Omicron subvariants XBB and BA.2.86, designated XDR, has been detected mainly in Brazil. In this study, we reconstructed the spatiotemporal dynamics and estimated the absolute and relative transmissibility of the XDR lineage. The XDR lineage displayed a recombination breakpoint in the ORF1a coding region, and the most closely related sequences to the 5’ and 3’ ends of the recombinant correspond to JD.1.1 and JN.1.1 lineages, respectively. The first XDR sequences were detected in November 2023 in the Northeastern Brazilian region, and their prevalence rapidly surged from <1% to 25% by February 2024. The Bayesian phylogeographic analysis supports that the XDR lineage likely emerged in the Northeastern Brazilian region around late October 2023 and rapidly disseminated within and outside Brazilian borders from mid-November onwards. The median effective reproductive number of the XDR lineage in Brazil during the initial expansion phase was estimated to be around 1.5. In contrast, the average relative instantaneous reproduction numbers of XDR and JN* lineages were estimated to be 1.37 and 1.29 higher than that of co-circulating XBB* lineages. In summary, these findings support that the recombinant lineage XDR arose in the Northeastern Brazilian region in October 2023, shortly after the first detection of JN.1 sequences in the country. In Brazil, the XDR lineage exhibited a higher transmissibility level than its parental XBB.* lineages and is spreading at a rate similar to or slightly faster than the JN.1* lineages. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Department of Science and Technology (DECIT) of the Brazilian Ministry of Health (MoH), CGLab MoH (General Laboratories Coordination of Brazilian Ministry of Health), UK Health Security Agency (UKHSA) by the New Variant Assessment Platform (NVAP) project, the Japan International Cooperation Agency (JICA), CVSLR FIOCRUZ (Coordination of Health Surveillance and Reference Laboratories of Oswaldo Cruz Foundation), Centers for Disease Control and Prevention (CDC) grant, CNPq COVID 19 (MCTI402457 2020 0 and 403276 2020 9), INOVA Fiocruz (VPPCB 005 FIO 20 2 and VPPCB 007 FIO 18 2 30), FAPERJ (E26 210.196 2020), FAPEAM (Rede Genomica de Vigilancia em Saude REGESAM), FAPEAM (INICIATIVA AMAZONIA + 10 [grant: 01.02.016301.00439 2023 70]), FAPEAM INOVA FIOCRUZ INOVAcaO NA AMAZONIA (Chamada Publica no. 04 2022), NPI EXPAND U.S. Agency for International Development (USAID) implemented by Palladium (7200AA19CA00015), Centers for Disease Control and Prevention (CDC Grant Award 002174), and CNPQ CABBIO (grant number 423857 2021 5), and FAPERJ (grant number E 26 211.125 202). ### 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: This study was approved by the Ethics Committee of the FIOCRUZ (CAAE: 68118417.6.0000.5248 and CAAE:32333120.4.0000.5190), which waived signed informed consent for all participants. All methods followed guidelines and regulations of the Brazilian Ministry of Health. 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 This study's conclusions derive from examining 6,152 SARS-CoV-2 genomes from Brazil, which have been made publicly accessible via the EpiCov database from GISAID. These genomes were collected after October 1st, 2023, and submissions were recorded up until February 29th, 2024. The data can be accessed at . For our investigation of the XDR parental lineages and the phylogeographic analysis, we further included 20,226 global reference sequences collected after September 8th, 2023, and submissions were also recorded up until February 29th, 2024, which are available at . The XML files utilized throughout this analysis are openly accessible for review and replication of our methods at .