Spread of MERS-CoV Credit Dr Ian MacKay VDU MERS-CoV
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With the announcement of 9 new MERS-CoV cases over the past week in Saudi Arabia, and unconfirmed media reports of 7 additional cases in Taif, our need to better understand this emerging virus grows greater with each passing day.
Overnight The Lancet published a detailed report on the clinical symptoms and virological analysis of the 17th known MERS case – a 73 year old man from the UAE who was first treated at a hospital in Abu Dhabi and was then transferred by air ambulance to Germany on March 19th.
The patient, who developed renal failure and sepsis, died 7 days later (see WHO: Update On NCoV Fatality In Germany).
Unlike the SARS virus of 2003 – which carried roughly a 10% fatality rate – this new virus has killed a little over half of the cases that we know about. That percentage would drop should we find that surveillance has not been picking up milder cases.
While most of these cases have developed severe illness - some, particularly younger patients - have only experienced mild symptoms.
The clinical course of the illness appears different from what was seen with SARS – which was primarily characterized as a respiratory infection - whereas MERS-CoV appears to cause a more systemic infection, and often results in renal failure.
In today’s study we learn that doctors found the highest concentration of MERS coronavirus in samples taken from the patient’s lower respiratory system, but also found lower amounts of the virus in the patient’s urine, and stool. No virus was detected in the patient’s blood, however.
The detection of the virus in the patient’s urine helps explain the high rate of renal failure in MERS-CoV patients, and fits with what we learned previously about the virus’s receptor cell affinity.
Last March, in Nature: Receptor For NCoV Found, we learned that this novel coronavirus uses a well known cell surface protein called dipeptidyl peptidase 4 (DPP4) to enter and infect human cells.
This DPP4 cell surface protein (also called CD26) is evolutionarily conserved in other species, including bats (suspected of being potential host species), non-human primates, and other animals – all of which suggests that this virus might be able to infect a wide range of hosts.
In humans, DPP4 receptor cells are found in non-ciliated bronchial epithelial cells of the respiratory tract, and epithelial cells in the in kidney, small intestine, liver and prostate.
Locations consistent with the clinical picture of infection we’ve seen over the past year, that has often included both pneumonia and renal failure.
These researchers also compared this patient’s virus genome to four others already sequenced, looking at the number of genetic differences between them.
Viruses circulating in the wild pick up mutations at a roughly determinable rate.
Once you determine that rate (it varies among viruses), you can compare two or more similar viruses, and count the number differences between them.
With that information scientists can estimate how long it has been since they all shared a common ancestor.
These researchers calculate that these 5 isolates likely shared a common ancestor sometime in mid-2011. Nearly a full year before the first known cluster of human cases was reported in Jordan, in April of 2012.
For a more detailed explanation of how all this works, and previous work on the evolution of the MERS coronavirus, you may wish to revisit EID Journal: Deep Sequencing and Phylogenetic Analysis of NCoV.
While the full Lancet study is behind a pay wall, a fairly lengthy abstract is available (free registration req.). Follow the link to read:
Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection
Prof Christian Drosten MD, Michael Seilmaier MD, Victor M Corman MD, Wulf Hartmann MD, Gregor Scheible MD , Prof Stefan Sack MD, Wolfgang Guggemos MD, Rene Kallies PhD, Doreen Muth PhD, Sandra Junglen PhD, Marcel A Müller PhD, Walter Haas MD, Hana Guberina MD , Tim Röhnisch MD, Prof Monika Schmid-Wendtner MD, Souhaib Aldabbagh DVM, Prof Ulf Dittmer PhD, Hermann Gold MD, Petra Graf MD, Frank Bonin MD, Andrew Rambaut DPhil, Prof Clemens-Martin Wendtner MD
Summary
Background
The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus involved in cases and case clusters of severe acute respiratory infection in the Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the UK. We provide a full description of a fatal case of MERS-CoV infection and associated phylogenetic analyses.
<SNIP>
Interpretation
We have provided the first complete viral load profile in a case of MERS-CoV infection. MERS-CoV might have shedding patterns that are different from those of severe acute respiratory syndrome and so might need alternative diagnostic approaches.
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