Phylogenetic tree inferred using MrBayes  for the concatenated coding regions of 105 MERS‐CoV genomes or partial genomes sampled from humans and camels. We employed a codon‐position‐specific GTR substitution model with gamma‐ distributed rates amongst sites. Displayed is the majority‐consensus of 10,000 trees sampled from the posterior distribution with mean branch lengths. Posterior support is shown for nodes where less than 0.90. Sequences sampled from camels are denoted with a yellow circle, those from humans with a green circle. Sequences new to this study are labelled in bold. The cluster comprising viruses isolated from the Jeddah/Makkah hospitals in April 2014 are highlighted with a red box and those from the Prince Sultan Military Medical City, Riyadh in March, April 2014 are highlighted in blue. For comparison the Al‐Hasa 2013 hospital outbreak is highlighted in yellow and the 2013 Hafr‐Al‐Batin community outbreak in green.
Background. In spring 2014, a sudden rise in the number of notified MERS-Coronavirus infections occurred across Saudi Arabia with a focus in Jeddah. Hypotheses to explain the outbreak pattern include increased surveillance, increased zoonotic transmission, nosocomial transmission, changes in viral transmissibility, as well as diagnostic laboratory artifacts.
Methods. Diagnostic results from Jeddah Regional Laboratory were analyzed. Viruses from the Jeddah outbreak and viruses occurring during the same time in Riyadh, Al-Kharj, and Madinah were fully or partially sequenced. A set of four single nucleotide polymorphisms distinctive to the Jeddah outbreak were determined from additional viruses. Viruses from Riyadh and Jeddah were isolated and studied in cell culture.
Results and conclusions. Up to 481 samples were received per day for RT-PCR testing. A laboratory proficiency assessment suggested positive and negative results to be reliable. Forty-nine percent of 168 positive-testing samples during the Jeddah outbreak stemmed from King Fahd Hospital. All viruses from Jeddah were monophyletic and similar, while viruses from Riyadh were paraphyletic and diverse. A hospital-associated transmission cluster, to which cases in Indiana/USA and the Netherlands belonged, was discovered in Riyadh. One Jeddah-type virus was found in Riyadh, with matching travel history to Jeddah. Virus isolates representing outbreaks in Jeddah and Riyadh were not different from MERS-CoV EMC/2012 in replication, escape of interferon response, and serum neutralization. Detection rates and average virus concentrations did not change significantly over the outbreak in Jeddah. These results suggest the outbreaks to have been caused by biologically unchanged viruses in connection with nosocomial transmission.