A pandemic risk assessment of middle east respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia

Eifan, Saleh A.; Nour, Islam; Hanif, Atif; Zamzam, Abdelrahman M.M.; AlJohani, Sameera Mohammed

MERS-CoV pinpointed a zoonotic introduction of a novel coronavirus probably originating from bats into human populations (Sharif-Yakan and Kanj, 2014) . The zoonotic origin of MERS-CoV was bolstered via phylogenetic analysis and elucidated a very proximal phylogenetic similarity with the bat Betacoronaviruses: BtCoV-HKU4 and BtCoV-HKU5 ( van Boheemen et al., 2012) as well as identified of the cellular receptor . However, contact frequency between human and bats is highly limited in Arabian Peninsula. Subsequently other intermediate hosts were proposed, such as camels and goats (Raj et al., 2014a,b) . MERS-CoV was found circulating in dromedary camels from last 20 years (Corman et al., 2014) , and MERS-CoV neutralizing antibodies were detected in camels (Reusken et al., 2013; Milne-Price et al., 2014) . These findings indicated that camels could serve as the intermediate host for MERS-CoV zoonotic infections in Saudi Arabia, Oman, Jordan, and United Arab Emirates. On the other hand, human-to-human transmission was frequently observed among MERS cases as most of the human infections were recorded among health care workers and within households proposed a close contact transmission (Hunter et al., 2016; Sharif-Yakan and Kanj, 2014) . The World Health Organization (WHO) has reported 1038 MERS cases, mostly occurred in Arabian Peninsula involved 460 deaths from Saudi Arabia . Consequently, Saudi Arabia was considered as the epicenter of MERS-CoV infections (Alqahtani et al., 2017) . Subsequently several studies investigated the existing status and future evolution of pathogen to confront the probable outbreaks by studying MERS-CoV transmission (Breban et al., 2013; Poletto et al., 2014; Kucharski and Althaus, 2015; Abolfotouh et al., 2017) . The current study examined the level of heterogeneity in MERS-CoV transmission via cluster analysis relying on the geographical distribution of MERS cases since it could clarify the linkage between epidemic status and geographical separation of clusters (Cauchemeza et al., 2016) . One useful indicator that is used to check viral transmissibility is the basic reproduction number (R 0 ) representing the number of secondary cases due to each index case in a fully susceptible population because no approved vaccine is available (Breban et al., 2013) . Basic reproduction number sets the infectious agent's potential to start an outbreak. When R 0 is >1 epidemics takes off and the epidemic can diminish and die out when R 0 is less than 1 (Chang, 2016) . Moreover, reproduction numbers can be estimated at various times during an epidemic. It can be estimated at the beginning of an outbreak (initial reproduction number) or at any time during the outbreak (time-dependent reproduction number). Several methods are used to evaluate the initial reproduction number involving attack rate analysis, exponential growth (EG) method, maximum likelihood (ML) estimation and sequential Bayesian (SB) method (Obadia et al., 2012) . However, the timedependent reproduction number can be computed by averaging over all transmission networks compatible with observations using the time-dependant method (Wallinga and Teunis, 2004) . The attack rate method requires the least information, but it can be used only when the epidemic has finished, and additionally no further intervention can be conducted during the entire outbreak course. Thus, the use of this method is mostly limited to definite settings as schools or hospitals. In EG method,