Friday, 18 September 2015

Happy 3rd birthday Middle East respiratory syndrome coronavirus (MERS-CoV)...

It has been 3-years since Prof. Ali Mohamed Zaki sent his email to ProMED notifying them, and the world, of a novel coronavirus (15-Sept-2012). That email was published 20-Sept 2012.[1,7,8] 

Two years ago at this time we had 138 cases and 58 deaths, last year 856 cases with perhaps 306 fatal (36%). Today, we have heard of 1,588 cases worldwide of which at least 551 (35%) have been fatal.[2,3] A higher proportion of fatal cases occur in the Kingdom of Saudi Arabia (KSA) than were recorded in the 2015 South Korean outbreak. The type and extent of a nation's community that has comorbidities may play a role in these differences. The young seem nearly untouched by MERS. To date, 26 countries have harboured a MERS-CoV infected person and 13 of those have hosted ongoing transmission.[4]

Thankfully, the diagnostic tools described very early on are as useful today as they were in 2012.[5,6]

Three years on we still see no sign of that virus patenting issue manifesting into a real problem.[3] 

For me, this past year in MERSville has been about:

  • How amazing it was that MERS cases didn't occur during or as a result of one of the world's largest mass gatherings, the Hajj. Really. Amazing.
  • The absence of asymptomatic cases included in reporting from KSA. The World Health Organization's (WHO) definition of a case does not rely on the presence of symptoms but on the presence of virus or past viral infection. Withholding or not seeking these data produces an overstated value for the proportion of cases that die from infection and could confound efforts to interrupt transmission during an outbreak. In reality, the higher percentages may just be what we should expect among infection of older males and females with one or more comorbidities
  • The continuing appearance of large hospital-based MERS-CoV outbreaks driven by circumstances we create through unsatisfactory understanding of respiratory viruses, as well as poor preparation for their arrival in an emergency department. This occurred again in South Korea and Riyadh over the past year as it did in Jeddah the year before. In South Korea, the financial, economic, social and trust impacts were significant; communication once again a big loser from public health authorities and governmental agencies
  • The big question over our MERS-CoV antibody detection tools' capabilities. Can they detect the prior presence of a MERS-CoV infection when that infection did not result in symptoms in its human hosts, or caused only very mild symptoms? A 4-week study enrolling the contacts of confirmed cases and collecting daily nose/throat swabs, weekly bloods, filling in a daily symptom and temperature diary, followed by an 8-week blood sample, would help address this I think
  • Slow acceptance that camels are the main, albeit sporadic, source of MERS-CoV spillover infections of humans. Bats may have been involved in the distant past but for 30 or more years we have strong data to say that a MERS-CoV (or closely related virus) has resided in and spread among dromedary camels in Africa and or the Arabian peninsula causing mostly a 'common cold' like upper respiratory tract illness. The precise role of importation on moving MERS-CoV around the region remains poorly explored
  • Other animals, on paper, look like they could host MERS-CoV, but experimental infection studies are still lacking. Similarly, a camel birth cohort study (h/t @newprof1) would add additional information to the story of how this virus spreads between camels in herds or holding pens after importation or during festivals
  • We did not see any resolution to the missing data from 2014 - despite assurances from the KSA MOH.[12] Comprehensive data on cases that were just 'found' - remained incomplete.[11] Also, trying to identify deaths from among previously announced MERS cases is a task fraught with frustration, despair and dismay. And then there are the unexplained errors and differences in reporting when comparing MOH data to World Health Organization data. Yes, those cases that are reported are likely to be the tip of an iceberg of indeterminate size, but at least get right what is being reported-or...GASP...fix it up later
  • It was reported that among those humans listed as being 'asymptomatic' - over three quarters of such cases, when later interviewed, recalled having symptoms.[6] This, to me, casts a darker shadow over the quality of other clinical and epidemiology data too
  • We still have not seen any data from the testing of human samples, prospectively or retrospectively, from non-Arabian countries that play host to high numbers of MERS-CoV antibody-positive camels, for example, Egypt, Sudan, Somalia or Ethiopia
  • In the past year we learned that MERS-CoV variants, like other CoV variants, can recombine when multiple variants co-infect the same host (probably in camel herds but perhaps in crowded hospital outbreaks in places like Riyadh which appears to be a nexus for mixing of variants [13,14]) producing a new variant.[9,10] To date there has been no proven impact on clinical presentation or course, virus reproduction or immunomodulation or transmission. But have wee looked hard enough lately? While it is not immediately obvious from observing whole genome sequences - most of the kind of sequencing produced since MERS-CoV was discovered - sites of recombination can be predicted when we look with more specific software tools. Yet, what happens if this recombination happens between a contemporary human/camel variant and a more ancestral camel variant? Could the resultant recombinant virus change in transmissibility or become more or less clinically severe? Is that recombination scenario even possible? Are even older bat variants too genetically distinct to allow easy recombination? It is important we find out more about the diversity of MERS-CoV and CoVs among camels outside the Arabian Peninsula and seek them out in other animals there too. Just as it is important to measure what is happening in people there
  • Advances in therapeutic antibody preparations and in vaccine candidates. It remains to be seen whether camels will respond as immunologically required for a camel-based vaccine to prove effective, but as Ebola virus disease showed us, there is obvious benefit to having a ready-to-deploy arsenal of weapons in case of invasion by a viral foe that just 'shouldn't be capable of doing that thing'

It would be stupid to predict what will happen with MERS and MERS-CoV in the next 12 months. We can take some educated guesses though. 

But for now the focus is still largely on what the KSA will do about the problem on their doorstep. It may also be that MERS-CoV cases are percolating outside the Arabian Peninsula without our knowledge. Let's not leave this virus to its own device any longer. Let's act to make sure it doesn't comes back to bite us. The clues are all there. There are patterns that are clearly visible. Let's get the work done ahead of the panic for a change. How about we meet back here this time next year, same batch channel, same camel topic?

References...

  1. http://www.promedmail.org/direct.php?id=20120920.1302733
  2. https://flutrackers.com/forum/forum/novel-coronavirus-ncov-mers-2012-2014/146270-2012-2015-case-list-of-moh-who-novel-coronavirus-mers-ncov-announced-cases?t=205075
  3. http://www.who.int/csr/don/17-september-2015-mers-saudi-arabia/en/
  4. http://virologydownunder.blogspot.com.au/2015/09/mers-around-world.html
  5. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20285
  6. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20334
  7. Happy 1st birthday Middle East respiratory syndrome coronavirus (MERS-CoV)
    http://virologydownunder.blogspot.com.au/2013/09/happy-1st-birthday-middle-east.html
  8. Happy 2nd birthday Middle East respiratory syndrome coronavirus (MERS-CoV)...
    http://virologydownunder.blogspot.com.au/2014/09/happy-2nd-birthday-middle-east.html
  9. http://biorxiv.org/content/early/2015/06/12/020834
  10. http://mbio.asm.org/content/6/5/e01280-15
  11. http://virologydownunder.blogspot.com.au/2015/03/where-did-mers-cov-comorbidity-and.html
  12. http://virologydownunder.blogspot.com.au/2014/09/mers-cov-data-request-response-from.html
  13. http://www.ncbi.nlm.nih.gov/pubmed/24055451
  14. http://mbio.asm.org/content/5/1/e01062-13.abstract