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Withheld Riyadh and Medina MERS Sequences Raise Concerns
Recombinomics Commentary 09:00
May 27, 2014

The recent report of a MERS cluster in Iran, which may involve Umrah pilgrims, and the sequences from a cluster in The Netherlands which did involve Umrah pilgrims has raised concerns that a second sub-clade has emerged in the Kingdom of Saudi Arabia (KSA).  The second sub-clade has been confirmed by sequences (by the US CDC) from exports from Riyadh (to Munster, Indiana with onward transmission to Chicago, Illinois) and partial Medina sequences by Erasmus Medical Center, EMC, (to The Hague and Zwolle in The Netherlands).  The sequences in the US and the Netherlands match each other, but are distinct from any published sequences from KSA because sequences from Riyadh (with almost 140 confirmed cases since April) and Medina (with 30 confirmed case in the same time frame) have been withheld.

Samples from these cases have been sent to the Drosten lab in Bonn, but the data has been withheld.  A letter to Promed (posted April 26) noted that three nearly complete sequences from cases from two hospitals in Jeddah would be posted at the Drosten website.  Additional comments indicated that spike gene sequences from 25 additional cases matched the posted sequences, which raised concerns that a novel Jeddah sub-clade had emerged.  However, the explosion in Jeddah sequences was attributed to poor infection control and increased testing.

When additional sequences were not released, Recombinomics contacted Christian Drosten, who explained his travel had led to delays in releases and he would instruct the lab to release additional sequences, which was immediately followed by the release of three additional sequences, which included sequences from a third hospital in Jeddah as well as a case from Mecca.  These three sequences provided additional support for clonal expansion of a novel sub-clade since they matched the first three sequences and were unlikely due to poor infection control because of the sequence from Mecca.

However, Drosten suggested that additional sequences would not be forthcoming unless there were significant changes.  Thus, the most recent sequences at the Drosten web-site are from collections on or before April 15.  More recent sequences linked to Jeddah were provided by US CDC sequences from exports to Athens, Greece and Orlando, Florida, which matched the six sequences from Jeddah and Mecca.

In addition to the sequences matching the Jeddah sub-clade, the CDC also released sequences from another health care worker (HCW) from KSA, who had traveled to Muster, Indiana.  Thus case had worked in a hospital in Riyadh and the sequence was most closely related to prior sequence from Riyadh and Medina.  However, this sequence had a number of novel polymorphisms not reported in any prior MERS sequence, as well as polymorphisms found in prior sequence from Hafr Al-Batin, as well as the Jeddah sub-clade, signaling recombination.  Moreover, the ORF8b sequence had a stop codon at position 78, leading to a truncated protein of 77 amino acids, instead of the wild type protein with 112 amino acids.

This sub-clade was unique until EMC publishes partial sequences from the two pilgrims, which matched the Munster sequence, signaling the emergence of a second sub-clade, which was circulating in Medina and Riyadh.  This match raises concerns regarding the withheld sequences from cases in Medina and Riyadh.  The explosion oin cases in Riyadh is almost as high as the cases in Jeddah, and the detection of the same sequences in two pilgrims with infections that likely originated in Medina raises serious concerns since pilgrims who perform Umrah in Mecca and Medina will have potential exposure to both sub-clades.

The sequences from Median and Riyadh, as well as additional cases in Mecca should be released immediately.

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