Abstract
<title>Abstract</title> <p>Global SARS-CoV-2 surveillance based on consensus genome sequences has enabled unprecedented tracking of viral spread and evolution but provides limited resolution of intra-sample diversity and limited sensitivity for the reliable detection of recombinant genomes. Here, we analyzed 3,360 SARS-CoV-2 genomes generated through regional surveillance in northeastern Germany (Mecklenburg–Western Pomerania) between 2022 and 2025. Reconstruction of local spatio-temporal variant dynamics revealed substantial lineage diversity, regional deviations from global circulation patterns, and periods of intense co-circulation favoring co-infection and recombination. To systematically identify recombinant genomes, we implemented a two-stage framework combining high-sensitivity consensus-based screening (REcombination BARcode detector REBAR) with targeted raw-read validation. Among 61 candidate recombinants, 21 were supported by read-level evidence, including 17 previously unrecognized genomes. Recombinant breakpoints clustered in functionally relevant genomic regions, particularly around ORF1b and the spike gene, indicating non-random patterns of genome exchange. Despite frequent co-infections, only a small subset of recombinants showed evidence of onward transmission, suggesting that successful establishment represents a major constraint on recombinant SARS-CoV-2 evolution. Our findings demonstrate that recombination-aware genomic surveillance complements routine consensus genome surveillance by resolving intra-sample diversity and recombinant diversity while remaining scalable for population-level implementation.</p>