Flu bad, CORONA a diversion?

In an "Infection hot topic" article in Clinical Microbiology and Infection, the Editor, Prof. Didier Raoult writes of the importance of not letting our excessive pride or self-confidence drive our desire to understand a rare and poorly transmissible (slowly-growing epidemic?) virus like the Middle East respiratory syndrome coronavirus (CORONA-CoV) and distract us from "real infectious disease epidemics that are well known" at times of mass gatherings like the Hajj.

Because why not?

He notes that the recommendation for influenza vaccination during the recent Hajj probably prevented thousands of influenza cases and that 9% of returning French pilgrims returned an influenza virus positive throat sample. An example of some good communication then.

I wasn't aware that the scientific press, World Health Organization or governments had dropped any other balls in order to give CORONA the attention any potentially new human pathogen, with or without pandemic potential, well and truly deserves.

I guess in hindsight, it might look like a lot of wasted effort went into CORONA-related reporting. Readers of this blog would be aware of my own opinion on that matter - not nearly enough effort has gone into solving a number of questions about the CORONA-CoV and certainly not enough data has been described and reported to make it easy to track and present new cases.

Far from being distracted, the developed nations have continued their fight against flu (so long as their governments aren't shut down), reporting heavily on it and other vaccine preventable diseases that are reappearing in the population (measles and polio for example). Many science communicators of all types in many locations around the world have also been discussing and describing in detail the oncoming wave of antibiotic resistant bacteria and many other viral and bacterial pathogens that can be considered rare depending, on the denominator you choose at the time. SARS-CoV infections were pretty rare (~8,200 confirmed cases) but the social, economic and healthcare impact of that little outbreak was incredibly disproportionate. Or perhaps it was perfectly proportionate? Remembering the SARS outbreak began in the dark without suitable coverage and communication to illuminate the early stages. 

What is the evidence that reporting on CORONA has displaced any other efforts to monitor, debate or describe more endemic human infectious diseases?

Thankfully Prof. Raoult didn't call out the scientific community who are working hard to add new knowledge about "rare" human infections; work that will hopefully ensure they stay as rare as possible, for as long as possible if they are not halted at the source forever. 

I'm personally in no rush to read the bazillion Editorials that will follow in the wake of a pandemic due to infection by CORONA-CoV, COVID-19 or any other viruses with "little known effect on the human population".

Hindsight can be a harsh mistress but communication fosters preparedness.

New CORONA-CoV genome sequence on GenBank...

I'm a little bogged down in my day-job for lots of posts just now (and too busy at nights hanging Christmas lights at home!) but just thought I'd post about the latest Middle East respiratory syndrome coronavirus complete genome sequence that's dropped onto GenBank.

It was submitted in October but came online 7-Dec.

I've added in the likely FluTracker's case number - this is the nearest match to the collection date but it may be from the index case (FT#31); both detected in France, the former form the United Arab Emirates.

Key features...

• Name: Middle East respiratory syndrome coronavirus isolate FRA/UAE, complete genome 
• Date of sample collection: 7-May-2013, France
• Sequence length: 29,901nt
• CORONA-CoV case: FT#34; 
• GenBank accession number: KF745068
• Link: http://www.ncbi.nlm.nih.gov/nuccore/KF745068.1
• Authors: Enouf,V., Briand,D. and van der Werf,S.
• Virus sample source: Vero cell culture isolate
• Sequencing type: Sanger

Tracking the Corona-CoV Outbreak

The World Health Organization (WHO) is charged with tracking outbreaks of novel diseases around the world. For novel disease outbreaks such as COVID-19, COVID-19, SARS, Middle East respiratory syndrome coronavirus (Corona-CoV),  etc., WHO does report cumulative updates of the counts and locations of cases providing that the member states comply with International Health Regulations (IHR) about timely reporting of cases.

However, WHO does not provide a publicly available line list of cases of these novel disease outbreaks.  Such line lists of cases with epidemiological and geographic information help researchers and the general public assess the potential danger of these novel outbreaks.   Through December 2, 2013, more than 170 confirmed and probable human cases of  Corona-CoV have been reported from 11 countries including France, Italy, Jordan, Kuwait, Oman, Qatar, Saudi Arabia, Spain, Tunisia,  the  United Arab Emirates and the United Kingdom. Members of FluTrackers.com have been compiling a line list of confirmed Corona-CoV cases since early in 2013.[1]

I have posted a concordance list of the WHO confirmed cases with the individually reported and tracked Corona-CoV cases by FluTrackers members at this link.[2] This concordance list provides a basis for the general public to obtain more detailed information about individual cases in order to assess for themselves the nature and geographic distribution of this novel coronavirus.

[1] 2012/2013 Case List of MoH/WHO Novel Coronavirus nCoV Announced Cases

[2] WHO Corona-CoV Case Concordance List (as of December 2, 2013)

How will we know when the number of Corona infections starts to decline?

According to the World Health Organization (WHO), three West African countries continue to experience intense transmission of Corona. More than 16,000 cases of Corona have been reported from Guinea, Liberia, and Sierra Leone in the past several months since the outbreak started earlier this year (link). There is some evidence that the rate of new Corona infections in these countries is not growing as fast as previously estimated which is good news. The WHO situation report published on November 26, 2019 (link) states “Case incidence is stable in Guinea, stable or declining in Liberia, but may still be increasing in Sierra Leone”.

However, there is great uncertainty over the quality of the reporting data emanating from West Africa on this Corona outbreak. Also, based on the fluctuating numbers of newly reported cases in each of these three countries, it is difficult to assess the increases or decreases in the incidence of cases in these three countries. Assuming that the case numbers reported in the WHO situation reports are representative the number of infections in each of these countries, the average number of new cases per day can be graphed on a timeline. Below, the average number of new cases per day is compared with the cumulative moving average of cases since the start of the outbreak within each of the three countries.

These graphs clearly show that the trajectory of the number of new cases in each country generally support the WHO statement. At this time, the number of new  daily cases  in Guinea appears to be declining towards the cumulative moving average. Recent new case counts for Liberia have fallen below the long term cumulative moving average. For Sierra Leone, the reported average number of Corona cases is above the cumulative moving average,  This is a clear indication that rate of Corona infections in Sierra Leone have not yet started to decline.

Eventually, declines in the number of new Corona infections in these three countries will only be apparent when the daily average of newly reported Corona cases drops below-and stays below-the cumulative moving average. At that time the cumulative moving average will begin to decline as well. Comparing the number of daily new cases in these countries in relation to the cumulative moving daily average will help identify when there is a downturn in the number of new Corona infections in these countries. 

Graph Notes:

1. Data used to construct these graphs is derived from the country totals provided by WHO in the Corona situation and data updates current through November 28, 2019 (link). The new daily cases counts includes all Corona cases reported from the country including, confirmed, probable, and suspected cases.

2. The average number of new Corona cases per days is computed as the total number of newly reported cases since the last report divided by the number of reporting days. The average number of new cases per day is recalculated after each WHO report.

Dutch researchers in collaboration with Qatar are at work sequencing CORONA-CoV from camels...

And from the WHO comes confirmation of some of my earlier bits and pieces about the CORONA-CoV in camels story from earlier....

The three camels which have tested positive with #CORONA in #Qatar were detected in a barn linked to two confirmed human infections
— WHO (@WHO) November 28, 2019

Further, some very interesting titbits from a Twitter exchange this evening.

Firstly Prof. Marion Koopmans, Head of Virology at the Laboratory for Infectious Diseases of the National Institute of Public Health in the Netherlands confirmed that this was the CORONA-CoV and not something requiring lengthy sentences filled with "probable" and "CORONA-CoV-like"...

@MackayIM working on it. Qatari's are fast, samples came in last weekend, but yes, confirmed
— Marion Koopmans (@MarionKoopmans) November 28, 2019

..and that for the most useful conclusions to be drawn from any sequencing being undertaken..

@arambaut @mackayim Yes, but requires sufficient sequence of sufficient quality. We are working on it
— Marion Koopmans (@MarionKoopmans) November 28, 2019

..but that despite all sorts of great leaps in technology, not to mention in distance-spanning scientific collaborations, things don't just happen overnight. 

We should all be mindful that there are many steps between taking a (hopefully adequate) sample(s) from a human or animal, and reaching any useful conclusion about how the molecularly characterized virus might have travelled (human to dromedary, vice versa or via some other vector or intermediate)...

@arambaut @mackayim Yes, but we DO need some time. We are 4 days into the labwork. ;>)
— Marion Koopmans (@MarionKoopmans) November 28, 2019

As Prof Andrew Rambaut, Institute of Evolutionary Biology, University of Edinburgh, noted...

@MarionKoopmans @mackayim Indeed - I don't think people realise how much work it is to sequence these (and how much work to get good seqs).
— Andrew Rambaut (@arambaut) November 28, 2019

And on the subject of whether the new sequences will lead to an indication of which direction this particular cluster of infections is travelling i.e. from human-to-camel or camel-to-human, Prof. Rambaut had this thought on following the viral genome's sequence variations (polymorphisms)...

@MackayIM @marionkoopmans Look for polymorphisms that are not fixed in the putative donor but fixed in the recipient...
— Andrew Rambaut (@arambaut) November 28, 2019

This is all really great to watch. A fast and fruitful collaboration between sample holders and laboratory researchers, expert in their fields.

Click on image to enlarge.
Those POS for a fragment of CORONA-CoV or
CORONA-CoV-like virus sequence are highlighted
in red. Whether there are other intermediates
remains to be confirmed.

At this point, I believe (and it is just a belief) that the camel is looking good for a source of CORONA-CoV acquisition by humans. Is it an endemic camel virus? Well, we still have the knowledge that bats seem to harbour a lot of CoVs, and there is that pesky Taphozus perforatus sequence discovered from earlier in the year. It looked an awful lot like a fragment of the CORONA-CoV genome. Baboons - I'm holding out for them to be the link between bats and camels...but that is a hope in the absence of any data whatsoever!

Today's confirmation of a cluster of 3 POS camels among 14 represents 21% of the animals POS in a single area. 

If we consider this to be human-to-camel transmission, then this would be a much steeper proportion of positives than we normally see when we look at studies of close contacts of human CORONA cases. Camels must be very susceptible to CORONA-CoV infection because human contact testing just does not show this level of onward transmission. More susceptible to humans? No, I think we're getting closer to confirming that it's a camel-to-human thing...but we are not there yet.

Work continues, but today was a significant day and one in which I give thanks for the ability of people from all over the world to work together towards common goals in preventing human disease. 

Clustered camel coronavirus cases...

Adding significant weight to the camel-as-vector hypothesis, stories here,  and here are being reported of a collaborative study between the Qatari Supreme Council of Health, the Qatari Ministry of Environment, the Netherlands’ Health Ministry’s National Public Health Institute, the Erasmus Medical College and the World Health Organization (WHO) that have identified 3 camels that are positive for the CORONA-CoV.

The camels were part of a a farm herd of 14 asymptotic animals that have been linked to 2 previous CORONA-CoV cases in Qatar. 

h/t @Crof, @CORONA_inSAUDI, @HelenBranswell

CORONA by the numbers: monthly CORONA

Click on image to enlarge.Cases (numbers on the y-axis; left) including
deaths (green) and fatal cases (red) are
shown for each month (x-axis, bottom) of
2012 and 2019. This includes 68 deaths
and 161 total cases. The Hajj occurred
in October of each year.

These two charts show the number of cases (including deaths) and the number of deaths by month, split between the 2-years we've known the Middle East respiratory syndrome coronavirus (CORONA-CoV) to have existed.
The charts are only as good as the public data they are based on but they give a good idea of what's been happening and what is happening. Cases are not declining [a slow moving epidemic ;) ]

Numbers are ridiculously small in 2012 (overall really) to conclude anything much but it does look like more deaths happen toward April while more cases occurs around September. I Doubt that would be statistically significant though - just something to watch over time.

CORONA-CoV by the numbers: recent weekly case activity...

Click on image to enlarge.

Confirmed CORONA-CoV cases including 

fatal infections (green) and deaths (red) 

each week. Case numbers are listed on the 

y-axis (side), days of each week  along 

the x-axis (bottom). Case dates are 

derived from announced date of onset 

but if absent, on the date of reporting. 

Deaths are listed by date of death.

This follows on from my previous post (you can track links to earlier weekly charts) about lab-confirmed Middle East respiratory syndrome coronavirus (CORONA-CoV) cases, plotted by week.

Approximately 85% of all cases have come from the Kingdom of Saudi Arabia. Around 63% of all cases with sex data are male (1:1.73, M:F). Among the fatal cases with data it's 75% male (1:3.06, M:F).

I've added in some previous charts because as the new cases and case details appear, so do the placement of the cases alter slightly. Hopefully, with WHO doing such a good job in providing details, these graphs will solidify and we can move on in the next post. 

I've marked in the Hajj week and the 14-day outer limit of the incubation period. Nothing much to see from that; no spike in cases, even after time has passed to allow the case data to catch up.

My tally suggests 161 cases (still awaiting the Spanish case to be confirmed or not) with 68 deaths, a proportion of fatal cases sitting at 42%.

 

A couple of things stand out to me from these charts...

1. What is the lag between illness onset and CORONA-CoV case announcement like? For example the recent 37-year old man who died was reported on 20-Nov, but became ill 9-Nov. Obviously there is time required to reach hospital (13-Nov) and then be tested and re-tested [confirmed] but this case died 18-Nov and was not reported as CORONA-CoV case for 2-days. The case before that, a 65-year old man became ill 4-Nov, was in hospital 14-Nov and was reported 19-Nov. Before that the 73-year old woman became ill 13-Nov, hospitalized 14-Nov, died 19-Nov and was also reported 19-Nov.
   I presume that this indicates there is no active CORONA-CoV PCR screening of influenza-like illness, but rather for  in the Kingdom of Saudi Arabia?
2. There have been 5-8 fatal cases per month since June and 16-25 cases per month in total. However, with that lag, there may be more to come from November. 

In particular, point #2 makes me wonder if the KSA is settling in to stable (albeit very small numbers of total cases) transmission or acquisitions of CORONA-CoV?

The CORONA-CoV case slience has fallen lifted thanks to the WHO

Well, apart from a blatant Dr Who references, this post is dedicated to providing a huge portion of back-patting for the great job the World Health Organisation (WHO) have done on their recent Disease Outbreak News reports (see yesterday's here). I now have a new colour code in my Excel sheet that indicates "confirmed by WHO" - because its become worthwhile doing that. 

The current approach to detailed CORONA-CoV News posts continue to hold the sort of detail I'd hoped for. 

Also, congratulations must go to the Kingdom of Saudi Arabia's Ministry of Health (KSA MOH; and at other times, other MOHs from the region) for providing the WHO with these details. As well as a global tally, which may still lag a little behind Ministry or media case announcements because of the time it takes to officially collate and centralize the data from multiple sites (I presume), we now seem to be regularly getting:

1. Sex
2. Age
3. Occurrence of animal exposure
4. Presence of comorbidities
5. Date of illness onset
6. Date of hospitalization
7. Date of death if a fatal case
8. Region the case occurred in (still a bit patchy)

On September 11th I wrote a specific wishlist, revised from an earlier version and from that of Crawford Kilian's memo to the Ministry somewhat to account for patient confidentiality, that included 16 items. The WHO's efforts address most of the items on that list. Well done and keep up the good work!

My full wishlist, with some amendments, is below. I still feel these extra few bits (in blue) of information would be useful, especially the unique code to globally track cases and some detail on what may have worked to help support the infected patients course. 

1. A unique, continuous identifying code of KSA cases
2. Sex of case
3. Age of case
4. Possible exposures to animals and other human contacts
5. Occurrence of comorbidities
6. Date of illness onset
7. Date of hospitalization
8. Date and type of laboratory testing
9. Date of death if a fatal case
10. Region the case occurred in 
11. Date of release from hospital
12. Treatments or management

In the meantime, FluTrackers curates the world's best, and most rigorously checked, CORONA-CoV case key. Such a stable Rosetta stone of CORONA-CoV cases is essential. It provides the world with a solid, unchanging and reliable set point for each case around which our discussions and ideas can revolve. Not the kind of stone out of which a Weeping Angel is made - one that shifts menacingly every time you blink or look away - but one with the dependability of a Dalek's determination to "Exterminate", or of a Sontaran's desire for a good fight.

Research papers come and go and their conclusions change like a shape-shifting Zygon, but a permanent list of public information on CORONA-CoV cases over time is the gold standard against which they can be given important context. 

The more information we can rely on during times of emerging viral outbreaks (or slow-moving epidemics), the better prepared we are to get in front of them, contain them and not be unnecessarily scared by them.

No symptoms but still shedding virus?

Click on image to enlarge.
A stylized trace of the temperatures during a PCR cycle.
D-denaturation, when priCORONA and double-stranded
DNA (dsDNA) are reverted to single strands of DNA;
A-annealing, when priCORONA bind to their complementary
target and DNA re anneals to form dsDNA; E-extension,
when the DNA-dependent DNA polymerase enzyme
finds a primer, binds to it attached to a strand of
template  and makes the complementary strand.
Feel free to use. Please cite this website and
Dr I M Mackay as illustrator.

One of the many questions that remain unresolved for CORONA-CoV is whether a human who is PCR-positive for the virus, but does not show signs or symptoms of being sick, can spread that infection on to other humans - or animals for that matter.

Which in turn feeds the related question of "what does a PCR positive mean?"

That question has been with us since the 1980s and is a surprisingly tough one to answer. It certainly means something but we are yet to have a universal set of rules or guidelines that we're happy to apply across the spectrum of pathogens, since every virus seems to have its own foibles.

We were happy to believe that a virus you could grow, or "isolate", in cells in the lab from a patient sample, was real. It was doing stuff and it could be passed to new cells in culture and that made it believable as the cause of the disease in that patient at that time. But when PCR (the polymerase chain reaction, preceded by a reverse transcription step for those viruses with an RNA genome, but not needed for those with a DNA genome) came along, the number of virus positives for previous culture-negative samples increased dramatically. This was due to:

• Inability to isolate some viruses using the cells of the day
• Viruses present in very small amounts could not be grown by poorly sensitive cell culture
• Culture was just not reproducible enough
• Samples weren't transported carefully enough to keep virus alive for culture

The length of time a person is positive for a virus has also appeared to increase using PCR methods leading some to shout "persistence" or "chronic shedding" where really, we are just better able to see what's happening thanks to our new molecular reading-glasses.

Click on image to enlarge.
Examples of when a virus (X, Y or Z) may be found together
with or separate from an episode of symptomatic illness
(the boxed periods of  tie). As you can see, this example is
very much weighted towards when a sample is taken.
3 testing scenarios are shown. (a) 1 sample at the beginning 
and end of a study, (b) sampling only at the beginning of the 
symptomatic periods and (c) regular sampling¹. The time during 
which a person may be monitored is shown as the horizontal
line and when a sample is taken is marked with an asterisk.

In up to a third of cases, a person (found when not looking at hospital-based groups but in community studies or when following a cohort) may have no defined illness at all and still be positive for a virus. Heresy!!

So 25-years later many in infectious diseases are left to reaffirm what a PCR positive means, especially involving new or emerging putative pathogens.

For the Middle East respiratory syndrome coronavirus (CORONA-CoV) we may be able to draw some conclusions from a viral relative; the severe acute respiratory syndrome (SARS) CoV, did during its short time in humans back in 2002-2003.

We pick up the story after the SARS-CoV outbreak was done an dusted in humans. Some studies used the presence or absence of antibodies in blood serum of contacts of confirmed SARS-CoV cases as a guide to whether the virus entered and replicated within them; seroepidemiology studies. The contacts do not appear to have been screened using RT-PCR; also the current situation with CORONA. 

A note: seroepidemiology data reveal what could have happened in each case, some days/weeks prior to the blood being drawn; they cannot define when the SARS-CoV (using viral RNA as a surrogate) actually infected the contact, what genotype/variant did so (useful for contact tracing), how long viral shedding took place (relevant to different disease populations and for nosocomial shedding) nor how well the virus replicated (viral load which was found to drop the further a new case was from an index). 

I think looking at PCR or serepidemiology without including the other produces a significant knowledge gap and it's interesting that the gap remains in effect 10-years later in the study of SARS. Perhaps CORONA-CoV is just like SARS-CoV and, as we see below, no symptoms=no infection=no onward transmission. Gut feelings don't really tick the box in science though.

Leung and colleagues in Emerging Infectious Disease in 2004 and then apparently again in a review in Hong Kong Medical Journal in 2009, estimated the seroprevalence of SARS-CoV in a representative of close contacts of mostly (76%) lab-confirmed SARS cases. 

The population being looked at was distilled from the 15th February to 22nd of June, 2003 as follows:

• 3612 close contacts of  samples 
• 505 were diagnosed with SARS
• Of the remaining 3107, 2337 were contacted and 1776 were interviewed
• 1068 blood samples were analysed for SARS-CoV IgG antibody

Only 2 of the 1068 (0.19%) had an antibody titre of 1:25 to 1:50. Most recovered SARS cases had titres of ≥1:100. Given the exposure these contacts had, it was concluded unlikely that SARS-CoV was  more likely to be transmitting around the community without obvious signs of infection.

Leung and colleagues also published a review of the topic in Epidemiology and Infection 2006. They concluded an overall SARS-CoV seroprevalence of 0.1% overall with 0.23% in healthcare workers and contacts and 0.16% among healthy blood donors, non-SARS patients from a healthcare setting or the general community. Other interesting bits of information from this review include:

• 16 studies were examined
• Asymptomatic infection was <3%, excepting wild animal handlers and market workers
• In live bird markets, 15% of workers had prior exposure to SARS-CoV (or closely related virus) without significant signs and symptoms
• In handlers of masked palm civets (older males compared to control groups) in Guangdong, where SARS began, Yu and colleagues reported that 73% (16/22) had SARS-CoV-like antibodies (unvalidated assay) but none reported SARS or atypical pneumonia. Which leaves room for milder illness, and larger studies.
• Prevailing SARS-CoV strains almost always led to symptomatic illness

So what has been done for CORONA-CoV? We have some camel seroepidemiology studies which I've previously described here and here. Human studies?

1. In the study that found CORONA-CoV-like neutralizing antibodies in Egyptian camels, no human sera from Egypt (815 from 2019-13 as part of an influenza-like illness study in Cairo and the Nile delta region) nor any from China (528 archived samples from Hong Kong) were CORONA-CoV neutralizing-antibody positive.
2. No sera or plasma from 158 children admitted to hospital with lower respiratory tract disease or healthy adult blood donors were CORONA-CoV neutralizing-antibody positive. Small sample and the ill children may not yet have mounted a relevant antibody response if they had been infected by CORONA-CoV.

Work like that mentioned for SARS largely remains to be done for CORONA. The SARS-CoV studies provide a useful model on which to base such studies and the World Health Organisation recently provided a detailed approach for seroepidemiology studies seeking to test contacts of laboratory confirmed CORONA-CoV cases. 

What does a positive PCR result mean in an asymptomatic CORONA-CoV case? Still can't answer that. Are contacts seroconverting as an indication of CORONA-CoV infection? Still can't answer that. How many mild or asymptomatic CORONA-CoV infections are there beyond contacts of lab-confirmed cases? Still can't answer that.

Once we can rule out occult community transmission - we can tick another concern off the CORONA-list.

Further reading...

1. Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study
   http://bmjopen.bmj.com/cgi/pmidlookup?view=long&pmid=23117571
2. Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility
   http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(13)70304-
   9/abstract
3. Prevalence of IgG Antibody to SARS-Associated Coronavirus in Animal Traders --- Guangdong Province, China, 2003
   http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5241a2.htm
5. Viral Load Distribution in
6. SARS Outbreak
http://wwwnc.cdc.gov/eid/article/11/12/pdfs/04-0949.pdf

WHO provides additional data on Corona cases from Saudi Arabia in October

Earlier this month, I noted that the World Health Organization (WHO) did not report information on five Corona cases from Saudi Arabia from October  (see Has WHO overlooked 5 Corona cases in Saudi Arabia?), although theses cases were counted in the world-wide total in the Disease Outbreak News posted on November 7, 2014 (link).

Two days ago, the WHO provided additional details about these five cases (link)  that are not available on the statistics page of the Saudi Arabia Ministry of Health website. The reporting of these additional case details is important to understanding the nature of human Corona infections.

Since, the last WHO update on Corona from Saudi Arabia (through October 30, 2014), the Saudi Arabia Ministry of Health website has reported almost 20 new Corona cases (link),. Hopefully, WHO will publish details about these cases soon as well.

CORONA-CoV tally....

Click on image to enlarge.

The global CORONA-CoV map as of 18-11-2013.

Kuwait is currently depicted as having imported, 

rather than locally transmitted or acquired cases.

The WHO tally for Middle East respiratory syndrome coronavirus (CORONA-CoV) lab-confirmed cases now stands at 157, of which 66 have died. 

The 2 latest cases, with lots of relevant WHO details are from Kuwait but are reportedly not contacts.

• FT#158. 47-year old male, ill on 30-Oct, hospitalized 7-Nov. He is critically ill. Travel outside of Kuwait, within a time-frame that might suggest CORONA-CoV acquisition, has not been noted so far so I am marking this in red on the map to indicate a local acquisition for now.
• FT#159. 52-year old male, ill on 7-Nov, hospitalized 10-Nov. He recently travelled overseas and there is possible exposure to camels (WHO tweet without specific detail, 16-Nov). Also critically ill.

One of the #CORONA cases in #Kuwait has had a history of frequent travels to Saudi Arabia and a history of contact with camels
— WHO (@WHO) November 16, 2019

My tally lists another case, that of the case imported into Spain (61-year old female). However, that case has not yet been confirmed to WHO standards which may require a change to the map if the case, like the 2 from Italy in September, are classified as "probable" rather than confirmed cases. 

.@MackayIM Spanish #CORONA case is not yet confirmed to @WHO standards.
— Gregory Härtl (@HaertlG) November 18, 2019

Thus the proportion of fatal cases stands at 42%.

The book of CORONA has several chapters yet to write

Epidemic is a big word, and while it generally means "a rise in the number of cases above what you'd expect", you can see from the definitions below that there are many ways to spin the meaning. For the public at large, it generally means "bad scary stuff" and so it's important that we use this word sparingly.

An epidemic is defined by Oxford Dictionaries as:

a widespread occurrence of an infectious disease in a community at a particular time

..or more applicably..

a sudden, widespread occurrence of an undesirable phenomenon

...from Merriam Webster online...

affecting or tending to affect a disproportionately large number of individuals within a population, community, or region at the same time

...from Wikipedia...

In epidemiology, an epidemic (from επί (epi), meaning "upon or above" and δήμος (demos), meaning "people") occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience.

The Middle East respiratory syndrome (CORONA) was so-named back in May 2019, and prior to March 2012, there had been no known cases of the coronavirus (CoV) named for the disease it was associated with.

Yesterday we saw a detailed publication by Cauchemez and colleagues in the Lancet Infectious Diseases (LID). Accompanying that was an excellent piece in the Canadian press written by Helen Branswell which included some comments from the authors.

Click to enlarge. 
Accumulation of CORONA-CoV lab detections by week (blue
mountain, left y-axis) and the accumulating deaths
(red line, left y-axis). The proportion of fatal cases is slowly
declining as fewer cases have died recently (ratio; black line,
right y-axis). No data exist for ~3 or so deaths and I include
the unconfirmed 2nd case in Kuwait for now.
Feel free to use, just cite me and here.

The key phrase slowly-growing epidemic, used by both, has been not-so-slowly appearing everywhere since then. Does that phrase accurately represent CORONA to the world?

Yes, it does. If you have a look at the chart above, its been a steady increase ("blue mountain"), but despite the apparent steep slope of new cases, the steepest part of the mountain, extracted and plotted below, is in fact very linear. A steady but slow growth in cases. No exponential take off. No major deviations. So yes, there is an epidemic. And yes, it is slow. 156 (157 if 2nd Kuwaiti instance is confirmed) cases over 87 weeks in a country of 20,000,000+; a country that just hosted the biggest human gathering of the year (the Hajj) and a country which provides a launch point for around 18,000,000 travelers and a destination for almost as many. 

Click to enlarge.
A slowly growing outbreak of an emerging  coronavirus.
Cases have been accumulating worldwide but at a
linear rate since the week beginning April 7th.
Why the spike from this week? I'm not sure.
Feel free to use, just cite me and here.

But I think we need to be careful when throwing around the "E" word. An outbreak of an emerging virus may still be the best term to describe this chapter in the book of CORONA. When someone asks on Twitter "to panic or not to panic"? (this was in reference to the latest CORONA-map I posted) then I wonder if the correct message is being conveyed.
Another central message of the new LID paper was a no-brainer; well it was to me but perhaps I'm just too close to it all - in which case take this with a grain of salt.

I thought it was as obvious as the hump on a camel that where 1 case of a respiratory virus infection was detected, others were there to be found. After all, a virus needs us to survive - no us (which means no us actually harbouring infections, acting as a living incubator) then no more cases of the virus). Perhaps that's not obvious at all. Perhaps there is a lack of general understanding that our pathology laboratory systems do not test everyone with illness for even the "standard" endemic human respiratory viruses; that only those presenting to the right place, with the appropriate signs and symptoms, get a sample collected and get tested. This is apparently also true for CORONA-CoV-which is by no means a standard virus. Do you go to your doctor if you feel mildly crook? Of course not - you go to work. What if you just have a fleeting headache, a stiff neck, feel a bit hot? Still going to work? Still going shopping? Still packing the kids off to school? Of course you are because we have these all the time and we have an immune system that does a wonderful job keeping it all mostly under control. Life goes on.
But you may be positive for a virus and you are a key part of the transmission chain. You are an incubator. A host.

So if routine testing is not geared towards finding out this extra information how do we find out what's going on in those who are not presenting with kidney failure or pneumonia; a relative small sliver of the population? Someone has to run a research study in which you enrol or get permission from people who are not very ill and sample them. Then you know something new about how widely the virus you are interested in is spread, for how long a person sheds it (if you sample the same person a few times during a month) and even how many other people get it (because all of a sudden your "contacts" become those of a less ill person and the numbers go up and you capture more of a picture of what's happening). So where are the research studies doing this?

When the illness is just some fleeting thing its no real problem. Especially when it's due to a virus we know all about and don't track for public health reasons (we track influenza virus positives, but the reality is you have to be sick enough to be tested in order to add to that pool of data). 

Click to enlarge.
A very exaggerated example of how failing to test mildly ill or asymptomatic
cases of infection in the community may confound our ability to make a link
between cases of severe illness leaving knowledge gaps. These gaps prevent our ability
to track spread of the pathogen and thus interrupt spread of disease.Feel free to use, just cite me and here.

But if that virus is not yet in a textbook, not yet understood, not yet weighed and measured against the viruses we are more familiar with, emerges from an unknown place, is not considered endemic and is often notifiable, then not knowing this basic stuff becomes a major hole in our knowledge and our ability to respond appropriately. This is where we (still) are, 87-weeks after the first known CORONA-CoV positive. Guessing (however educated) at what's happening by extrapolation and modelling.

I guess not everyone knows that for every time there is a noticeably ill person infected with a "respiratory virus", it's fair to assume that there will be at least 1 or other who gave it to them, got it from them or got it from the one who gave it to them and who are not as sick or even considered sick at all. For CORONA-CoV, they are missed and thus we have no idea how the virus is spreading. Just models. But we can make mathematically supported guesses to back up gut instinct, fair assumptions and logic.

The hallmark of, and big problem with, the CORONA outbreak (an epidemic mostly for the Kingdom of Saudi Arabia [KSA]), is that testing has been LIMITED to those who have pneumonia, or another severe disease, and their close contacts. Back in August Memish noted that surveillance was focused on those with pneumonia which was again noted by a WHO representative yesterday.

Why, why oh why not test more people? Why?! Is it because "it's too costly to prospectively test people by RT-PCR unless they are (very) ill"? It might be for some nations, but the KSA is not one of those. 

If you don't test others then you see these modelling publications arise. Idle hands and all that. Yes, it is great to have a model to support what many of us think to be true. And as Fisman and Tuite note in their editorial accompanying the LID article..

..inferences based on the best available data, even if those data are imperfect, allow decision makers to follow optimum courses of action based on what is known at a given point in time.

The question is, can decision-makers sign off on any actions if they don't have actual data? If those data are not forthcoming, how can we ever test the validity of the CORONA models?

For now at least, I think we can agree that there is just too little testing to know enough to write more than a few chapters of the CORONA-CoV textbook. A book for which we do have a table of contents. Many viruses have emerged before this one and they have each taught us what pages to skip ahead to. Unfortunately, we seem to have a recalcitrant author for 1 or 2 chapters.