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

From sequence data we identify at least 50 zoonotic introductions of MERS-CoV into humans from the reservoir (Figure 1 ), from which we extrapolate that hundreds more such introductions must have taken place (Figure 3 ). Although we recover migration rates from our model ( Figure S2 ), these only pertain to sequences and in no way reflect the epidemiologically relevant per capita rates of zoonotic spillover events. We also looked at potential seasonality in MERS-CoV spillover into humans. Our analyses indicated a period of three months where the odds of a sequenced spillover event are increased, with timing consistent with an enzootic amongst camel calves (Figure 2) . As a result of our identification of large and asymmetric flow of viral lineages into humans we also find that the basic reproduction number for MERS-CoV in humans is well below the epidemic threshold ( Figure 3 ). Having said that, there are highly customisable coalescent methods available that extend the methods used here to accommodate time varying migration rates and population sizes, integrate alternative sources of information and fit to stochastic nonlinear models (Rasmussen et al., 2014) , which would be more appropriate for MERS-CoV. Some distinct aspects of MERS-CoV epidemiology could not be captured in our methodology, such as hospital outbreaks where R 0 is expected to be consistently closer to 1.0 compared to community transmission of MERS-CoV. Outside of coalescent-based models there are population structure models that explicitly relate epidemiological parameters to the branching process observed in sequence data (Kühnert et al., 2016) , but often rely on specifying numerous informative priors and can suffer from MCMC convergence issues.