Reconstructing relative transmission rates in Bayesian phylodynamics: Two-fold transmission advantage of Omicron in Berlin, Germany during December 2021.

Phylodynamic methods have lately played a key role in understanding the spread of infectious diseases. During the coronavirus disease (COVID-19) pandemic, large scale genomic surveillance has further increased the potential of dynamic inference from viral genomes. With the continual emergence of novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) variants, explicitly allowing transmission rate differences between simultaneously circulating variants in phylodynamic inference is crucial. In this study, we present and empirically validate an extension to the BEAST2 package birth-death skyline model (BDSKY), BDSKY[Formula: see text], which introduces a scaling factor for the transmission rate between independent, jointly inferred trees. In an extensive simulation study, we show that BDSKY[Formula: see text] robustly infers the relative transmission rates under different epidemic scenarios. Using publicly available genome data of SARS-CoV-2, we apply BDSKY[Formula: see text] to quantify the transmission advantage of the Omicron over the Delta variant in Berlin, Germany. We find the overall transmission rate of Omicron to be scaled by a factor of two with pronounced variation between the individual clusters of each variant. These results quantify the transmission advantage of Omicron over the previously circulating Delta variant, in a crucial period of pre-established non-pharmaceutical interventions. By inferring variant- as well as cluster-specific transmission rate scaling factors, we show the differences in transmission dynamics for each variant. This highlights the importance of incorporating lineage-specific transmission differences in phylodynamic inference.