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Paradigm Shift Intervention Monitoring
Did Jeddah MERS Sub-Clade Spread To Mecca?
C.D.: There has been a lot of discussion about whether the virus has mutated to pass more easily from human to human. But we have sequenced three genomes from samples taken early in April in Jeddah, where many of the cases occurred, two more from later in the Jeddah outbreak, and another one from a patient in Mecca. They all look completely normal.
The above comments (in red) are from a letter from Christian Drosten to ProMed published on April 26, which gave some background on delays in the release of Jeddah MERS sequences (Easter holiday and time to go through customs), but noted that his lab had nearly complete sequences on three Jeddah cases from early April and none had a receptor binding domain change in the spike gene. He also noted that partial sequences from 25 additional Jeddah case exactly matched the spike gene in the three full sequences. Moreover, he made the three full sequences available on his website and included a phylogenetic tree showing that all three sequences were virtually identical.
This identity raised concerns that a novel sub-clade had emerged, since the three sequences were from two different hospitals and all three were distinct from all published human MERS sequences (had 11 polymorphisms found in all three Jeddah sequences and absent from all published sequences).
Drosten explained away the identities with the above comment suggesting the two hospitals had poor infection control, leading to cross contamination between the two hospitals, leading to the same sequences in all three cases.
His updated comments (in blue) cited three additional sequences (two from later cases in Jeddah and one from a case in Mecca), which like the first three “look completely normal” raising concerns that the three more recent sequences belong to the same sub-clade as the first three sequences from early April (Jeddah_C7569, Jeddah_C7149, Jeddah_C7770). This match would signal the spread of the same novel sub-clade from Jeddah to Mecca.
These concerns could be addressed by the uploading of the three recent sequences to the same page as the first three sequences. Alternatively, the concerns could be addressed with a phylogenetic tree at the Drosten website or the website of Andrew Rambaut, which was also cited in the ProMed letter as a resource for information on the Jeddah sequences A tree with all three sequences was initially posted on the Rambaut website, but was subsequently removed. It has been replaced with a phylogenetic tree with one of the Jeddah sequences, as well as several Taif camel sequences, which are now published and are closely related to the the human Jeddah sequences, but none of the camel sequences have the S gene polymorphisms, Q833R, or Orb8b polymorphism, L6Q (both of which are in all three human Jeddah sequences).
The initial data released over a week ago suggested Jeddah data would be promptly posted at the two websites (as was done for SARS sequences in 2003). Recombinomics has e-mail both labs regarding the absence of any new Jeddah/Mecca data at either website, as well as the extent of the relatedness between the first three Jeddah sequences and the more recent sequences from Jeddah and Mecca, but neither lab has responded by the time of publication of this commentary.
The three recent sequences, as well as the 25 spike gene sequences, should be released immediately.