MERS-CoV spillover at the camel-human interface

Gytis Dudas; Luiz Max Carvalho; Andrew Rambaut; Trevor Bedford; Ali M. Somily; Mazin Barry; Sarah S. Al Subaie; Abdulaziz A. BinSaeed; Fahad A. Alzamil; Waleed Zaher; Theeb Al Qahtani; Khaldoon Al Jerian; Scott J.N. McNabb; Imad A. Al-Jahdali; Ahmed M. Alotaibi; Nahid A. Batarfi; Matthew Cotten; Simon J. Watson; Spela Binter; Paul Kellam

. CC-BY-NC 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/173211 doi: bioRxiv preprint Figure S5 . Monte Carlo simulations of human transmission clusters. From top to bottom each row corresponds to departures from completely random sequencing efforts with respect to case cluster size (bias parameter=1.0) to sequencing increasingly biased towards capturing large case clusters (bias=2.0, bias=3.0). Leftmost scatter plots show the distribution of individual Monte Carlo simulation sequence cluster size statistics (mean and skewness) coloured by the R 0 value used for the simulation. The dotted rectangle identifies the 95% highest posterior density bounds for sequence cluster size mean and skewness observed for empirical MERS-CoV data. The distribution of R 0 values matching empirical data are shown in the middle, on the same y-axis across all levels of the bias parameter. Under unbiased sequencing (bias=1.0) only 0.45% of simulations fit our phylogenetic observations, while 1.79% and 1.67% of simulations fit for bias levels of 2.0 and 3.0, respectively. Correspondingly, we estimate 11.6% support for a model with bias level 1.0, 45.7% support for a model with bias level 2.0, and 42.7% support for a model with bias level 3.0. Bins falling inside the 95% percentiles are coloured by R 0 , as in the leftmost scatter plot. While the 95% percentiles for R 0 values are close to 1.0 (0.71-0.98) for the unbiased sequencing simulation (i.e. uniform sequencing efforts, in which every case is equally likely to be sequenced), we also note that increasing levels of bias are considerably more to likely to generate MERS-CoV-like sequence clusters. The distribution of total number of introductions associated with simulations matching MERS-CoV sequence clusters is shown in the plots on the right, on the same y-axis across all levels of bias. Darker shade of grey indicates bins falling within the 95% percentiles. The median number of cross-species introductions observed in simulations matching empirical data without bias are 346 (95% percentiles 262-439). These numbers jump up to 568 (95% percentiles 430-727) for bias = 2.0 and 656 (95% percentiles 488-853) for bias = 3.0 simulations. Model averaging would suggest plausible numbers of introductions between 311 and 811.