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

Severe acute respiratory syndrome (SARS) coronavirus, a Betacoronavirus like MERS-CoV, caused a serious epidemic in humans in 2003, with over 8000 cases and nearly 800 deaths. Since MERS-CoV was also able to cause significant pathogenicity in the human host it was inevitable that parallels would be drawn between MERS-CoV and SARS-CoV at the time of MERS discovery in 2012. Although we describe the epidemiology of MERS-CoV from sequence data, indications that MERS-CoV has poor capacity to spread human-to-human existed prior to any sequence data. SARS-CoV swept through the world in a short period of time, but MERS cases trickled slowly and were restricted to the Arabian Peninsula or resulted in self-limiting outbreaks outside of the region, a pattern strongly indicative of repeat zoonotic spillover. Infectious disease surveillance and control measures remain limited, so much like the SARS epidemic in 2003 or the H1N1 pandemic in 2009, zoonotic pathogens with R 0 > 1.0 are probably going to be discovered after spreading beyond the original location of spillover. Even though our results show that MERS-CoV does not appear to present an imminent global threat, we would like to highlight that its epidemiology is nonetheless concerning. et al., 2004) and influenza A are able to jump species barriers but only influenza A viruses have historically resulted in pandemics (Lipsitch et al., 2016) . MERS-CoV may join the list of pathogens able to jump species barriers but not spread efficiently in the new host. Since its emergence in 2012, MERS-CoV has caused self-limiting outbreaks in humans with no evidence of worsening outbreaks over time. However, sustained evolution of the virus in the reservoir and continued flow of viral lineages into humans provides the substrate for a more transmissible variant of MERS-CoV to possibly emerge. Previous modeling studies (Antia et al., 2003; Park et al., 2013) suggest a positive relationship between initial R 0 in the human host and probability of evolutionary emergence of a novel strain which passes the supercritical threshold of R 0 > 1.0. This leaves MERS-CoV in a precarious position; on one hand its current R 0 of ∼0.7 is certainly less than 1, but its proximity to the supercritical threshold raises alarm. With very little known about the fitness landscape or adaptive potential of MERS-CoV, it is incredibly challenging to predict the likelihood of the emergence more transmissible variants. In light of these difficulties, we encourage continued genomic surveillance of MERS-CoV in the camel reservoir and from sporadic human cases to rapidly identify a supercritical variant, if one does emerge.