Viral Crossroads: Genomic Surveillance of SARS-CoV-2 Variants and Recombinants in Northeastern Germany (2022–2025)
Global SARS-CoV-2 consensus genome-based surveillance provides scalable virus monitoring but has limited ability to intra-sample diversity and reliably detect arising recombinant genomes. Here, we analyze 3,360 SARS-CoV-2 genomes generated through a regional surveillance program in northeastern Germany (Mecklenburg–Western Pomerania) spanning 2022–2025. Reconstruction of local spatio-temporal dynamics of variant circulation, revealed substantial lineage diversity, region-specific deviations from global circulation patterns, and phases of intense co-circulation that create favorable conditions for 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 recombinant genomes, 21 were supported by read-level evidence, including 19 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 show signatures of onward transmission, suggesting that successful epidemiological establishments represents a major constraint on recombinant SARS-CoV-2 evolution. Together, our findings demonstrate that regional genomic surveillance can uncover fine-scale evolutionary dynamics and recombinant diversity that remains obscured in routine lineage-based monitoring. The integration of consensus-based screening with focused raw-read validation provides a practical and scalable path to recombinant-aware genomic surveillance of SARS-CoV-2.
Global SARS-CoV-2 consensus genome-based surveillance provides scalable virus monitoring but has limited ability to intra-sample diversity and reliably detect arising recombinant genomes. Here, we analyze 3,360 SARS-CoV-2 genomes generated through a regional surveillance program in northeastern Germany (Mecklenburg–Western Pomerania) spanning 2022–2025. Reconstruction of local spatio-temporal dynamics of variant circulation, revealed substantial lineage diversity, region-specific deviations from global circulation patterns, and phases of intense co-circulation that create favorable conditions for 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 recombinant genomes, 21 were supported by read-level evidence, including 19 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 show signatures of onward transmission, suggesting that successful epidemiological establishments represents a major constraint on recombinant SARS-CoV-2 evolution. Together, our findings demonstrate that regional genomic surveillance can uncover fine-scale evolutionary dynamics and recombinant diversity that remains obscured in routine lineage-based monitoring. The integration of consensus-based screening with focused raw-read validation provides a practical and scalable path to recombinant-aware genomic surveillance of SARS-CoV-2.
Institute of Bioinformatics, University Medicine Greifswald