Tuesday, 3 September 2013

How MERS may be SARS, but we don't really know

On July 26th, Prof Christian Drosten wrote in Lancet Infectious Diseases about some similarities and differences between the diseases Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), each linked to a zoonotic coronavirus (CoV) infection.

Drosten is senior author of the 2 publications papers describing gold-standard MERS-CoV laboratory diagnostic methods, all PCR-based, which afford excellent diagnostic and genotyping capabilities upon the user. Unfortunately we have not yet seen much use of the genotyping assays. He has also co-authored papers on the MERS-CoV receptor, viral replication, its naming, discovery of antibodies in camels and MERS case reports. He has an even bigger list of diverse publications on the SARS-CoV.

Drosten is well positioned to say that at first glance it is not the same beast but that we have many things to learn before we can be sure of that. 

Reviewing data from Assiri and colleagues from the same issue of Lancet, he noted that MERS and SARS have some similarities. Cases often presented with fever as a classifying symptom at presentation. Upper respiratory tract symptoms were not common (4-40% of cases had something that could identify an upper airway disease) and so most cases could be clinically differentiated from the common cold.

A major difference from SARS has been the high level of comorbidities associated with MERS cases. However, this needs to be interpreted with caution since for example, a third of people in a pre-MERS study of Saudi Arabian outpatient visits had diabetes, including more than half over the age of 50-years. In that context, the proportion of MERS-CoV positives among his group in the Kingdom of Saudi Arabia (KSA) population may not be so over-represented. It may simply flag the opportunistic nature of the virus. 


MERS also differentiates itself from SARS in its rapid progression to a fatal outcome; again this may be related to the population it is affecting the most; older males with comorbidities. Mechanistically, MERS-CoV differs in its cellular receptor (DPP4 vs ACE2 for SARS-CoV) and its greater replicative efficiency and ability to infect a wider range of cell types in the lower airways compared to SARS-CoV. And then there's the spelling, nucleotide and amino acid sequence differences too!


Drosten also poses some questions: 
  1. Can we rely on samples from the upper respiratory tract in which viral loads can be low enough to muddy the waters of result interpretation?
  2. We need serological assays and we need to define them using characterized cases. Then we need to roll them out at the population level to better define those icebergs that seem to be everywhere these days
Without further data, we're still left to ponder what would SARS have been like if the CoV got into the KSA? In fact, what do other respiratory viruses do to those with comorbidities in the KSA?

There are similarities and differences between MERS and SARS and between their viral causes. More work is needed. 

The best way to answer the question posed in Drosten's article would have been a direct comparison of the impact of the two viruses in the same population. Thankfully for the hosts, there has been no significant overlap between the 2 outbreaks so far.