The importance of utilizing travel history metadata for informative phylogeographical inferences: a case study of early SARS-CoV-2 introductions into Australia

Inferring the spatiotemporal spread of severe acute respiratory syndrome coronavirus 2 (SARS- CoV- 2) via Bayesian phylogeography has been complicated by the overwhelming sampling bias present in the global genomic dataset. Previous work has demonstrated the utility of metadata in addressing this bias. Specifically, the inclusion of recent travel history of SARS- CoV- 2- positive individuals into extended phylogeographical models has demonstrated increased accuracy of estimates, along with proposing alternative hypotheses that were not apparent using only genomic and geographical data. However, as the availability of comprehensive epidemiological metadata is limited, many of the current estimates rely on sequence data and basic metadata (i.e. sample date and location). As the bias within the SARS- CoV- 2 sequence dataset is extensive, the degree to which we can rely on results drawn from standard phylogeographical models (i.e. discrete trait analysis) that lack integrated metadata is of great concern. This is particularly important when estimates influence and inform public health policy. We compared results generated from the same dataset, using two discrete phylogeographical models: one including travel history metadata and one without. We utilized sequences from Victoria, Australia, in this case study for two unique properties. Firstly, the high proportion of cases sequenced throughout 2020 within Victoria and the rest of Australia. Secondly, individual travel history was collected from returning travellers in Victoria during the first wave (January to May) of the coronavirus disease 2019 (COVID- 19) pandemic. We found that the implementation of individual travel history was essential for the estimation of SARS- CoV- 2 movement via discrete phylogeography models. Without the additional information provided by the travel history metadata, the discrete trait analysis could not be fit to the data due to numerical instability. We also suggest that during the first wave of the COVID- 19 pandemic in Australia, the primary driving force behind the spread of SARS- CoV- 2 was viral importation from international locations. This case study demonstrates the necessity of robust genomic datasets supplemented with epidemiological metadata for generating accurate estimates from phylogeographical models in datasets that have significant sampling bias. For future work, we recommend the collection of metadata in conjunction with genomic data. Furthermore, we highlight the risk of applying phylogeographical models to biased datasets without incorporating appropriate metadata, especially when estimates influence public health policy decision making.