Monitoring viral evolution and epidemiological characteristics of SARS-CoV-2 during 2022–2023 using Integrated Genomic Surveillance

Abstract Background The continued emergence of SARS-CoV-2 variants with increased transmissibility and immunoevasive properties highlights the necessity to complement genomic surveillance with epidemiological data and laboratory-based assessment of viral phenotypes. Effective surveillance tools must be scalable, cost-efficient, and able to detect and characterize emerging variants in timely manner. Methods We utilized the Integrated Molecular Surveillance for SARS-CoV-2 (IMSSC2) network to conduct nationwide integrated SARS-CoV-2 genomic surveillance in Germany. SARS-CoV-2-positive samples from diagnostic laboratories were routinely subjected to whole genome sequencing. Epidemiological data from COVID-19 cases infected with BA.1, BA.2, BA.5.1, BQ.1.1, XBB.1.5, XBB.1.9.1, and XBB.1.9.2, notified between 1 December 2021 and 30 April 2023, were analyzed. Complementary, representative virus isolates were examined for immunoevasive properties and replication in human respiratory infection models. Results Lineage assignments of 4595 SARS-CoV-2 genomes indicate ongoing viral evolution with successive replacement of dominant variants from Delta to Omicron lineages BA.1, BA.2, BA.5.1, BQ.1, and XBB recombinants. Age-stratified epidemiological analyses show higher proportions of BA.1 and BA.2 infections in children. Multivariable logistic regression identifies male sex and increasing age as significant predictors of hospitalization. Phenotypic characterization suggests ongoing adaptation of Omicron variants BA.2, BQ.1.1, XBB.1.5, and XBB.1.9.2 to the upper human respiratory tract and enhanced propagation of XBB.1.9.2 in an alveolar infection model. Conclusion Integrated genomic, epidemiological and virological approaches enable early assessment of emerging SARS-CoV-2 lineages and demonstrate ongoing adaptation across the human respiratory tract. Our findings show that geographically representative, scalable surveillance provides robust insights into viral evolution, supporting sustainable surveillance beyond the acute pandemic phase.