Friday, 3 January 2014

Antibodies in 10-year old UAE camel sera suggestive, but not evidentiary, of the presence of MERS-CoV a decade ago

Click on image to enlarge. 
I've cobbled together a graphic of the assays
that have come from Prof Christian Drosten group and
colleagues, mostly for the detection and
confirmation of MERS-CoV in human samples.
632 of 651 (97.1%) dromedary camel serum samples collected in 2003 and 2013 in the United Arab Emirates (UAE) have been found to react with Middle East respiratory syndrome coronavirus (MERS-CoV) or key pieces thereof.

Meyer and colleagues from the Netherlands, Germany and the UAE also tested 16 control samples from German zoo camels but none reacted to MERS-CoV in their testing system. This indicates that the camels have not been infected by the MERS-CoV (or something very much like it) leading the authors to suggest that the virus is relatively isolated to Arabian peninsula's eastern far as we know from the testing performed to date. 

This is a potentially huge piece of good news because it suggests, to me at least, that there is a very strong chance that the spread of MERS-CoV can be contained. It will however, take a collaborative effort to "stamp out" MERS-CoV the same way SARS-CoV was stopped in its tracks (to partly quote Mike Coston) through effective infection prevention and control measures being created, implemented and enforced. 

In the absence of further testing from other regions around the world, we hold information in our hands that suggests a region-specific isolation to the MERS-CoV. And we know that right now it does not seem to be very good at all at transmitting from human-to-human. Perhaps reflecting that it is currently a camel virus and not a human one? Of course, it may never evolve into a human virus.

From what we do know today of the MERS-CoV, stamping out human infections may involve some of the following steps:

  • Being aware of the risk of contact between humans and camels and seeking to limit such contact if it could occur in the absence of suitable precautions including personal protective equipment
  • Testing camels for active infection, which may not result in notable disease in camels, and isolating those camels from other camel herds to try and "burn out" infection in camels altogether. The horse racing industry might have some good advice in this department
  • Learning more about all aspects of MERS-CoV acquisition, spread and disease in camels and perhaps in other animals. This will be influenced by future screening projects results which will hopefully identify any other animals that also a close relative/immediate ancestor that is passed to camels and then humans, or perhaps directly to humans
  •  Implementing ways to break the chain of spread from a putative other animal host to camels to people. 

Hopefully such steps could be achieved without any long term impact to camel interaction in the region as they are an essential source of social, economic and dietary enrichment.

A recombinant MERS-CoV Spike immunofluorescent assay was used to screen samples for reactive antibodies. Vero cell s expressing a recombinant Spike protein from MERS-CoV or HCoV-OC43 (used to detect cross-reactive antibodies) were fixed and then incubated with diluted animal or control serum samples (1:20 - 1:80 at 37'C for 60-min). Captured antibody was labelled with an anti-llama antibody fragment labelled with a fluorescent tag (FITC). A MERS-CoV human protein microarray assay was used to confirm screening results (I've noted this assay previously here). Virus neutralization studies were also conducted using a method I've previously written about

Meyer's study also screened 182 camel's faecal samples collected in 2013 using broad-ranging CoV RT-PCRs which, upon nucleotide sequence confirmation, yielded 2 bovine coronavirus (BCoV) positives, but no MERS-CoV positives. We learn from this that recently stored faecal samples can yield CoV RNA that can also be sequenced.

It's also worth a quick hop back to looking at the bigger picture of animal testing for a moment. Succeeding in detecting MERS-CoV RNA among the relatively small numbers of samples tested to date is akin to finding the Arkenstone among Erebor's piles of gold (even if it looked easy in the movie). Sure, a decent number of different animal species have been tested so far, but only small numbers from each. And even though there is a high proportion of camels with MERS-CoV (or its antigenic kin) antibodies, we still have to strike it lucky enough to sample during what may well be an acute virus replication period lasting only days to a couple of weeks. So far, it looks like luck has been as slippery as a woodland elf on a riverbank. Larger numbers of each animal species, camels especially, should land a hit or two in the near future I'm betting.

There is still much testing to be done, but perhaps it's possible to shut the gate before the camels have truly bolted.

Hat-tip to Helen Branswell on Twitter and her article here.