The global spread of Middle East respiratory syndrome: an analysis fusing traditional epidemiological tracing and molecular phylodynamics

Background Since its discovery in 2012, over 1700 confirmed cases of Middle East Respiratory Syndrome (MERS) have been documented worldwide and more than a third of those cases have died. While the greatest number of cases has occurred in Saudi Arabia, the recent export of MERS-coronavirus (MERS-CoV) to Republic of Korea showed that a pandemic is a possibility that cannot be ignored. Due to the deficit of knowledge in transmission methodology, targeted treatment and possible vaccines, understanding this virus should be a priority. Our aim was to combine epidemiological data from literature with genetic information from viruses sequenced around the world to present a phylodynamic picture of MERS spread molecular level to global scale. Methods We performed a qualitative meta-analysis of all laboratory confirmed cases worldwide to date based on literature, with emphasis on international transmission and healthcare associated infections. In parallel, we used publicly available MERS-CoV genomes from GenBank to create a phylogeographic tree, detailing geospatial timeline of viral evolution. Results Several healthcare associated outbreaks starting with the retrospectively identified hospital outbreak in Jordan to the most recent outbreak in Riyadh, Saudi Arabia have occurred. MERS has also crossed many oceans, entering multiple nations in eight waves between 2012 and 2015. In this paper, the spatiotemporal history of MERS cases, as documented epidemiologically, was examined by Bayesian phylogenetic analysis. Distribution of sequences into geographic clusters and interleaving of MERS-CoV sequences from camels among those isolated from humans indicated that multiple zoonotic introductions occurred in endemic nations. We also report a summary of basic reproduction numbers for MERS-CoV in humans and camels. Conclusion Together, these analyses can help us identify factors associated with viral evolution and spread as well as establish efficacy of infection control measures. The results are especially pertinent to countries without current MERS-CoV endemic, since their unfamiliarity makes them particularly susceptible to uncontrollable spread of a virus that may be imported by travelers.