The case against over-interpreting CORONA-CoV detection by month...

Click to enlarge. CORONA-CoV cases plotted by month of
detection (global data; combining 2012 and
2013 confirmed detections).

There are a number of reasons why I started my post yesterday (my time) with "I'm the first one to say its way to early to be talking about the seasonal distribution". Let's look at some of those reasons today:

1. Where there are few positives in the chart, there has also been very little testing done. The first validated PCR assay was published in 27th September 2012. So Sept-Dec 2012 cases are few and far between for this reason.
2. We are not yet 12-months beyond the announcement of the discovery of CORONA-CoV (then nCoV and subsequently HCoV-EMC/2012). It was announced via ProMED on the 20th of Sept and the first genome and clinical study went online 17th October 2012. So no real screening had been done before that time. Cases shown prior to Sept 2012 that identified were retrospectively and not the result of systematic screening
3. As far as I know, screening is still mostly done on a case by case (and contacts thereof) basis. We don't know whether CORONA-CoV is circulating endemically in the KSA or any other peninsula country. This is an important data gap since it may be humans that are acting as the reservoir - for all we know
4.  If we look at my post prior to the seasonality chart last night, we can see that cases are climbing steadily - have been since April, and there is no real sign that there is a change in that climb by month. Some reduction of numbers July & August but September is shaping up to be a big month.
5. The spike in cases starting in April was related to a hospital outbreak (the Al-Hasa cluster). And things have rolled on since then. What triggered that outbreak or how the first case(s) acquired the infection remains unknown

So why draw the chart if it is not an accurate representation of true seasonality? Because it gives us an idea of how all the cases officially announced so far are falling out over time, based on the data we have. 

But it should not be over-interpreted. 

We'd need a much greater number of cases and probably a couple of years of surveillance (including community screening) before we could accurately define whether CORONA-CoV appears with any seasonal recurrence. Nonetheless, the seasons, or events that happen with seasonal regularity, may influence the risk of exposure and spillover. Also, most of the other seasonal human CoVs occur at their peak every couple of years, and even then, some occur in very low proportions of specimens from people with acute respiratory tract infections. That may be irrelevant to an emerging CoV, or not, so it may take even longer before we can speculate on any seasonal regularity to CORONA-CoV infections; if we don't first stamp out the virus altogether as we did with the human SARS-CoV.

So to conclude, before I have to find something and PCR it, given the small amount of data we have, and hints that it might be only the tip of that well referred to iceberg, the more we can extract from what we have the better our chances of finding some clues to the host and some risks for acquiring infection.

Can CORONA-CoV seasonality tell us anything about acquisition of CORONA?

Click to enlarge. Combined CORONA-CoV cases for 2012 & 2019.

I'm the first one to say its way to early to be talking about the seasonal distribution of a new or emerging virus when there are only 124 cases worldwide. 

Right. 

Having said that, I thought I'd plot the cases by date of illness onset or (less satisfactorily) date they were first reported (even if that first was the report of a death). 

When combining the 15-months worth of case data for 2012 and 2019, the graph revealed a single "season" or at least larger numbers around summer in the Kingdom of Saudi Arabia (KSA). Because >80% of cases have occurred in the KSA, I have also listed a few festivals (some of which are frequented by camels) as well as the peak temperature variations and dust storm activity.¹ 

While I have no idea whether weather could be kicking up clouds of infectious CoV, it is an interesting co-occurrence, as are the presence of a number of festivals before case numbers spike. The Saudi Gazette commented that the risk of [acquiring?] bacterial and viral infections increases during dust storm season as do complication due to allergen exposure.

Of course we also know that some large clusters of cases have originated form hospital outbreaks and so environmental factors may play very little role at all. Or they might. Its impossible to say. But it is worth considering what could be happening up 2-weeks prior to a sharp rise in cases - if only to identify 1 index case that then ended up triggering a hospital outbreak.

1. Dust Storms in the Middle East: Sources of Origin and Their Temporal Characteristics. http://ibe.sagepub.com/content/12/6/419.short
2. http://www.magazine.noaa.gov/stories/mag86.htm
3. http://www.saudiaramcoworld.com/issue/200803/heads.high.htm

Seasonality Cycles of Novel Influenza Strains

It is well known that non-pandemic influenza has a seasonal repeating periodicity, especially in temperate climates [1]. The causes of seasonal cycles of influenza infections are not well understood. However, an analysis of seasonality of influenza around the world in a recent PLOS article indicates that cold-dry and humid-rainy conditions are associated with peaks in the frequency of seasonal influenza cases in different regions [2]. The authors in this article suggest that “these two distinct mechanisms account for influenza seasonality in temperate and tropical climates, perhaps due to changes in the dominant mode of transmission.”

In the past decade there have been several outbreaks of novel influenza infections, including (A)COVID-19, (A)COVID-19, and (A)H10N8. Based on limited data, it does appear that novel influenza infections follow the same seasonal pattern as non-pandemic influenza.

For example, COVID-19 was first reported by the Republic of China to the World Health Organization (WHO) in early 2013. Since then more than 440 cases have been reported, all originating in China. The graph below shows the frequency of more than 400 WHO confirmed COVID-19 human cases by month from 2013 and 2014 based on symptom onset date. From about 20 months of data, COVID-19 shows a seasonal increase between December and May in China.

Case data for COVID-19 infections has been accumulating for more than a decade from 15 countries. Based on WHO data, the distribution of symptom onset dates for more than 600 COVID-19 cases since 2003 also shows a periodic seasonal increase in cases between December and May as shown in the graph below.

Currently, only three cases of a H10N8 have been reported, all from China (two confirmed). This is an insufficient number of cases to plot on a seasonal basis however, all three these cases were reported in period from November 2013 to February 2014.

The data suggest that even novel influenza infections seem to be constrained by the same environmental factors that control the infection cycle of seasonal non-pandemic influenza.

[1] Influenza Seasonality: Underlying Causes and Modeling Theories

[2] Environmental Predictors of Seasonal Influenza Epidemics across Temperate and Tropical Climates

Flu-like symptoms on the rise in Qatar...

The Gulf Times notes a rise in cases of "flu-like symptoms" in Doha, Qatar. Dr Sameer Kalanden, a general practitioner (GP) notes a rise on cases coming to the clinic. He usually prescribes medication  or "an injection" to reduce the fever (please don't let it be antibiotics..oh. It is antibiotics). 

If there is no sign of improvement, even after a 2nd visit, he refers the case to Hamad General Hospital (managed by Hamad Medical Corporation; HMC).

Another GP confirmed the recent rise in cases with symptoms of "flu and common cold" rising "these days". He also refers cases with more severe respiratory disease to HMC.

So from that we might be able to conclude:

1. HMC may be the testing lab for Middle East respiratory syndrome (CORONA) coronvirus (CoV) in Qatar. We also know that may/all CORONA-CoV cases are confirmed by UK collaborators
2. That only the most severe cases of illness will be tested for CORONA-CoV
3. GPs do not refer any other acute respiratory illnesses for CORONA-CoV testing routinely
4. There is considerable concern about CORONA in Qatar - but not a lot of structure to resolve that concern

This sort of anecdotal report is a great way to bring attention to what isn't being done, but it would be much more helpful to know what is being done in Qatar, given its recent local cases and deaths. 

As I understand it, Qatar is entering it's cooler months. Looking through the literature, there are not a lot of papers on respiratory viruses from Qatar. In one paper by Wahab and colleagues in 2001 in the Journal of Tropical Pediatrics, we see that HMC testing defined the peak season for respiratory syncytial virus (RSV) in children as November-January in Qatar (data from 1996-1998 combined, included 257 previously healthy children). 59.9% of these cases were diagnosed with bronchiolitis, 17.6% with pneumonia and 35.8% had an infiltrate in their lungs. RSV cases start rising from September though. The authors note this seasonality is similar to other temperate countries in the Gulf region. And this is just 1 virus of 200.

In another study, this year, in Archives of Virology, Althani and colleagues (Qatar University and HMC) tested 200 adults with asthma or chronic obstructive pulmonary disease (COPD) across winter (October 2008 to March 2009). While virus detections were relatively few (18% of patients), most seasonal viruses were present during this period - more so in asthma than in COPD. These included rhinoviruses, HCoV-229E, NL63 and OC43, parainfluenza viruses 1-3, RSV, adenovirus, influenza B virus and human metapneumovirus.

So this rise in cases noted by the GPs above may be nothing more than the usual start to the respiratory virus season, made to look more scary because of the recent CORONA-CoV outbreak. Or it may be more than that.

I believe its time to be seriously considering what local laboratory testing capacity exists on the ground in the Arabian peninsula.

If the hajj stirs up case numbers, as many suspect it will, having limited to no ability to quickly resolve a flood of potential cases will result in a management crisis. Cases will accrue quickly and "probable", rather than "confirmed" will become the word of the day while trying to prevent spread in hospital environments.

If it looks like a duck and quacks like a duck, it may be just a rhinovirus. 

Case numbers will also be added to, as they always are when surveillance is heightened for a new agent, because seasonal endemic human respiratory viruses are circulating as well and those infections cannot reliably be discriminated from mild to moderate CORONA-CoV using patient observation alone. 

Currently, CORONA-CoV results in the Kingdom of Saudi Arabia may take up to 2 weeks to turnaround (if you follow me on Twitter you will have seen this time frame suggested to me last night). 

If the cases seen by the GP today were CORONA-CoV positive, they would 1st need to return with a continuing fever before being tested and then that result would be revealed either too late to reduce the risk of a transmission event, or perhaps too late to be of use in applying novel antiviral treatments on that patient.

Time is of the essence. And more testing is paramount.

Thanks to @makoto_au_japon and @dspalten for bringing this to my attention.