MERS is a respiratory disease and MERS-CoV is a respiratory virus... PART I

The disease

Definition time.

The Middle East respiratory syndrome (MERS) is a disease (a change in the body away from normal function towards abnormal function) comprised of a bunch of signs and symptoms (the syndrome bit) that is identified in patients who turn up ("present") to their doctor/clinic/hospital with signs (things the doctor can see or measure e.g. coughing, sneezing or a fever with a temperature about 38°C) and symptoms (things the doctor can't see that may still be measurable or not e.g. lung inflammation upon X-Ray, muscle aches or chills but no measurable fever). 

At the bad end of the disease spectrum, MERS is an acute community-acquired pneumonia (CAP; confirmed by X-Ray of the lungs) that progresses to be worse. "Worse" includes kidney failure acute respiratory distress syndrome, respiratory failure and multi-organ failure. MERS pneumonia cannot be told apart from acute CAP due to other causes.

Laboratory testing to confirm the presence of the agent you suspect, is essential. You can't confirm its absence, but you can say it was "not detected". 

MERS is a particularly nasty disease for those who already have a disease that is chronic. These include diabetes, kidney disease, heart disease, hypertension, lung disease, obesity, malignancy and those who smoke or use steroids. This appears to more often include older males around the Arabian peninsula in whom the coronavirus that is assumed to cause MERS (MERS-CoV), has had a big impact, associated with the most severe forms of the disease and death. Neonates, infants, toddlers and children (up to 14-years) are in the minority of MERS-CoV detection to date (14 of 361 with age data, or 3.9%).

Over 85% of patients with MERS (remember: the disease, not the virus) have a fever >38°C, cough and chills or rigors (shaking episode) and all have an abnormal 1st chest X-Ray.

Around half have a runny nose and about a third have malaise (feel rubbish) and myalgia (aching or sore muscles).

A quarter have diarrhoea and a fifth have sore throat, nausea or vomiting.[1]

The virus.

While it has not been shown conclusively in humans, the MERS-CoV has been shown to cause MERS or a similar, although milder form of disease, in Rhesus macaques given an unrealistically large and I would argue, unrealistically located (the trachea) dose of virus preparation. So we work under the assumption that the MERS-CoV causes the signs and symptoms listed above, and/or causes our immune system to respond in such a way that respiratory disease is what MERS causes.

We talk about MERS being caused by MERS-CoV.

We also talk about flu being caused by influenzaviruses. To confuse matters though, there is no single "common cold virus" that causes the common cold so we need to specify that common colds can be caused by any respiratory virus (there just happen to be more rhinoviruses than an other respiratory virus so they mistakenly wear the brunt of that burdensome label even though they are also the main viral cause of much more severe asthma attacks).

Breathing in versus ingesting.

The MERS-CoV presents first as an acute respiratory infection, with some other things that develop or are exacerbated (pre-existing diseases in particular).

Even when atypical disease presents first and respiratory disease follows, that may simply be explained by other preceding or concurrent infections. Take the recent Greek imported case of MERS from Jeddah, Saudi Arabia. He presented first in Saudi Arabia with fever and diarrhoea and was also subjected to an X-Ray and found not have no pneumonia. He had visited his wife in hospital there and she had been diagnosed with typhoid fever. He was also given antibiotics to combat that bacterium based on a positive test. He then travelled to Greece whereupon he presented to Athens hospital with fever and low blood oxygen levels indicative of viral pneumonia. That was confirmed by an X-Ray. This can be interpreted as an atypical presentation of MERS...or perhaps just MERS following typhoid or a even an acute viral gastroenteritis. Very little testing of faeces was described for the latter possibility and so we don't know. And into the void walks hand-waving.

Sources...

1. Middle East Respiratory Syndrome Coronavirus (MERS-CoV): A Perpetual Challenge
   http://www.annsaudimed.net/index.php/vol33/vol33iss5/631.html
2. A CASE OF IMPORTED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION AND PUBLIC HEALTH RESPONSE, GREECE, APRIL 2014
   http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20782

H5N1 case in Canada had been diagnosed with pneumonia...testing at the source would have been helpful

And now, from a fantastically detailed post onto ProMED by Fonseca and colleagues, we see that the H5N1 case was diagnosed with pneumonia.

On 28-Dec, the patient presented to a local emergency department.

"A chest X-ray and CT scan revealed a right apical infiltrate. A diagnosis of pneumonia was made; the patient was prescribed levofloxacin and discharged home."

One sad point made in the ProMED post which supports the need for constant viral vigilance the world over, coupled with the dissemination of those surveillance data, so that patient management anywhere in the world can be armed with the best possible decision-making information...

"The index of suspicion was low as travel was to an area in China where there have been no recent reports of the circulation of this virus, and coupled with no obvious exposure to poultry, the diagnostic work-up and consideration for A(H5N1) infection was very low"

As a recent J Virology article by Yu and colleagues highlights, when a sensitive testing method like the polymerase chain reaction (PCR; in this case RT-PCR because influenza viruses all have an RNA genome, not a DNA one) is applied to the search for a virus, it yields the kind of data that can:

1. Explain from where a virus emerges
2. Inform the search for disease aetiology - where are human cases getting infected from and if a zoonotic infection (from animals to humans), which animal(s) is the culprit?
3. Alert the world to any risks of infection when travelling to a certain area(s)
4. Allow the local health departments to mitigate the risk of their population acquiring infection by instigating controls (like live bird market closures). This has implications for the world since respiratory viruses have the potential (thankfully not realized for H7N9 or H5N1 to date) to spread more rapidly and efficiently that blood-borne or mosquito-borne or sexually transmitted viruses.
5. Permit understanding of how widespread (over what geographic area is it detected) a novel or emerging virus may be and how entrenched (is the same site repeatedly positive) it is

Not doing such testing, or using less sensitive methods will not yield this information. 

In Yu's study, testing of 12 poultry markets, mostly urban, and local farms linked to 10 human infections in Hangzhou, Zhejiang province around 4th to 20th April 2013 yielded signs of H9N2, H7N9 and/or H5N1 viruses in all markets. Poultry were often positive for H7N9 and H9N2 (this finding from individual RT-PCRs was confirmed using next generation sequencing), whereas human specimens were not. These levels hadn't been turned up when 899,000 bird were tested in 2013 using (perhaps) less sensitive methods.

I think with influenza, it may be safer to presume its everywhere until that presumption can be discounted. Clearly the conditions for influenza viruses to swap gene segments and sort themselves into new subtypes and variants are commonplace and frequent; these aren't just chance occurrences of different birds passing in the night via overlapping flyways. These feathered vectors are co-infected by 2 or more viruses at a time. Luck and the constraints of viral fitness are presumably the only things keeping H7N1, H5N9, H7N2 cases from dialing up in humans? What seems to be lacking is more molecular testing at the farms supplying the markets. Not just in Zhejiang, but all over the region.

As the authors noted, 100,000s of people visit these live bird markets each day and very few influenza cases seem to be due to them. Long may that last. But it's a tinderbox for which matches are already being struck; if the viruses should bud of that one-in-a-million variant that is enabled to readily spread from person-to-person, whooshka. 

More testing guys, keep testing.