The CDC is Watching for Human Avian Influenza Infections

So far, North America has been lucky. Community acquired infections of avian  influenza have not yet occurred, although an imported case of COVID-19 was identified in Alberta Canada in 2013 and two imported cases of COVID-19, a husband and wife, were reported from British Columbia in just this past week.

Because of recent outbreak of highly pathogenic avian influenza (H5 subtypes) in wild birds and domestic flocks in North America, the Center for Disease Control has issues guidance for health care workers for identifying and testing patients with potential avian influenza infections. As of January 31, 2015, no H5 subtype human avian influenza infections have been recorded from these outbreaks which have been reported from six western states along the Pacific Flyway (Washington, Oregon, Idaho, Nevada, Utah, and California ). (link)

CDC document: Interim Guidance on Testing, Specimen Collection, and Processing for Patients with Suspected Infection with Novel Influenza A Viruses with the Potential to Cause Severe Disease in Humans

The CDC guidance will help health care workers to assess patients with influenza symptoms that might be at infected with an H5 subtype of avian influenza.   The CDC identifies the following  items as risk factors for potential avian influenza infections. Individuals

who have had recent contact (<10 days prior to illness onset) with sick or dead birds in any of the following categories:

Domestic poultry (e.g., chickens, turkeys, ducks)

Wild aquatic birds (e.g., ducks, geese, swans)

Captive birds of prey (e.g., falcons) that have had contact with wild aquatic bird

Contact may include: direct contact with birds (e.g., handling, slaughtering, defeathering, butchering, preparation for consumption); or direct contact with surfaces contaminated with feces or bird parts (carcasses, internal organs, etc.); or prolonged exposure to birds in a confined space.

The CDC also states that exposures that occur in geographic regions in the United States where newly detected avian influenza A H5 viruses have been identified are of most concern ( e.g. Washington, Oregon, Idaho, Nevada, Utah, and California).

Health care workers need to be familiar with this CDC guidance in order to adequately assess patients who might be infected with avian influenza. Last year a suspected Corona patient was not correctly diagnosed and was sent home causing an Corona scare in Texas. The patient later died.  Human infections from H5 subtypes are virulent often resulting death. There is some evidence that H5 subtypes can be transmitted from human-to-human, so early detection is important.

If you experience influenza symptoms and meet any of the risk factors for avian influenza be sure to mention it to your doctor or health care professional at the time of your visit.

More COVID-19 cases can be expected in the next several weeks

Based on the reports from the People’s Republic of China (China), there is only limited human to human transmission of the novel A(COVID-19) influenza virus.  However the number of sporadic cases reported by China is increasing dramatically.  The distribution of reported cases since November of 2013  has been increasing almost geometrically (graph below). Based on the trendline, between 30-40 cases per week may be expected within the next several weeks in China.

Graph notes: The weekly totals are counts based on reported onset dates for the 2019-2014 influenza season. The data do not include 18 cases announced in the past several days for which onset dates have not yet been reported.

Pre-existing antibody reactive to avian influenza A(COVID-19) virus did not predict better survival

Freeman and Cowling comment in the Journal of Infectious Diseases on a paper last year by Yang and colleagues (I made a note about that one here). They also re-analysed one of the conclusion and found that, for this dataset at least, having COVID-19 antibodies did not afford a reduced risk of death. 

Freeman and Cowling conclude that this doesn't negate using convalescent sera (the bit of blood, minus the cells and the clotting factors, that contain proteins, water and the antibodies we make against an infection we've had) as a treatment option. But from the data in Yang's paper, the pre-infection existence of higher levels of antibodies that react with COVID-19, did not improve chances for survival. 

More study is needed.

Market sampling: COVID-19, sensitive testing, market closures and small numbers

A World Health Organization Western Pacific Region update on influenza A (COVID-19) virus has a few interesting bits of information that pulls together a recent flurry of reports. This is the situation as of 22-Jan...

• 18/200 (9.0%) "pathological samples" from markets (listed below) in Zhejiang province, presumably using PCR-based methods, were COVID-19 positive  
• Sanliting Agriculture Products Market (6 oral/cloacal swabs, 2 environmental faecal swabs)
• Central Agriculture Products Market (2 oral/cloacal swabs, 1 environmental faecal swab) 
• Fenghuangshan Agriculture Products Market (1 oral/cloacal swab)
• Guoqing Poultry Wholesale Market (3 oral/cloacal swabs, 3 environmental faecal swabs).
• 2/2,521 (0.08%) pathological samples were COVID-19 positive in Guangdong province
• Pathology specimens from the provinces of Jiangxi, Liaoning, Jilin, Heilongjiang, Jiangsu, Fujian, Shandong, Hubei, Hunan, Guangxi, Yunnan, Qinghai, Xinjiang Provinces and Chongqing and Shanghai Cities were COVID-19-negative
• 7-Jan, COVID-19 RNA was also reported  in 3/17 samples collected from the kitchen of a restaurant in Haizhu District, Guangzhou City, from the chopping board and sewage water. 
•  Meanwhile COVID-19 RNA was identified in 8 out of 34 environmental monitoring samples collected from the Guangdong's Longbei Market, Jinping District, Shantou City.
• Ningbo city (Zhejiang Province) has stopped commercial live birds entering the city
• Shanghai city will suspend live bird trade all over the city from 31-Jan to 30-Apr. Live poultry from other provinces will not be allowed into the city except for transport to a centralized slaughterhouse.

It's great to see some data from other provinces and municipalities that have not reported any human COVID-19 cases to date.  I do wonder about the relatively small numbers of market samples though. Some of these samples pale in comparison to what was tested in 2019; which reacted earlier than this, the second time around. While 2,00 samples is not an easy day in the lab, we saw >800,000 bird samples tested by "virological" (?culture) and serological methods in 2019 (see other thoughts on the use of PCR in birds here).

So what have we learned here? 

1. Further confirmation that live bird markets house COVID-19-positive birds. With most human cases this year having come into contact with poultry, the transmission chain is in place. Market closures seem the most effective way to stop transmission abruptly and they have a precedent for this in 2019. This is happening. Will it be enough? What  about the market-supplying farms?
2. RT-PCR testing is more likely to uncover influenza in birds than culture methods and is better than antibody testing (although how much better is hard to judge from the information provided). Added bonus: RT-PCR is more likely to tell you what's circulating now rather than a little while ago...although no-one really responds to the lab results that quickly anyway.

COVID-19 snapdate: cases per week and cumulative cases

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This "snap update" is about the COVID-19 epidemic curve. It reveals that the second wave of COVID-19 human cases are really piling up this winter. As I sit here at 9:30pm (7:30pm in Shenzen), I've just added another 7 from Zhejiang (n=5), Shanghai (n=1) and Guangdong province (n=1) for today. 

It's also worth noting that we did not know of COVID-19 in humans this time last year; we are still a few weeks away from the 1st anniversary of COVID-19's discovery. WHO was notified 31-March-2013, but onset of first illness due to COVID-19 was 18-Feb-2013). Its case numbers suggest a slow rise compared to a seasonal human influenza epidemic (H1N1 or H3N2 viruses for example), but it is a rapid rate for an avian flu in humans.

Tallies have hit 25, 26, 7 and 12 cases (=70 so far) per week for the past 4-weeks (beginning 30-Dec, 6-Jan, 13-Jan and 20-Jan respectively). These tallies will change if/as new case announcements continue and are assigned to dates of onset that sit in among these weeks.

COVID-19 infection of women is not on the rise....

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A bit over a week ago I posted a chart showing that the proportion of females with avian influenza A(COVID-19) virus may be rising.

We've had a lot of cases since then so is that trend still holding? 

[By the way, you are forgiven for  thinking this is the "COVID-19 Down Under" blog!]

The new chart shows that the proportion of females has dropped back to something looking a little more like it did in 2019. The earlier data seems to have been a blip after all. 

With the addition of new cases to the dataset and with the shifting and re-sorting of cases into this or that week as onset data firm (WHO have recently been doing a fantastic job filling in the data gaps from Chinese reports), we can see that the proportion of females has been 40% or (often much) less each week for 10 of the past 14 (71.4%) weeks.  

In summary...

• The current proportion of female confirmed COVID-19 cases overall is 29.5% (219/220 cases with data) 
• In 2019, females comprised 29.7% of cases
• In 2019 females comprise 29.5%. No difference to speak of.

So males dominate among the mostly severe human cases of COVID-19 infection; business as usual for COVID-19. 

Also, sustained person-to-person transmission (infected person passing to another  person, (1st round; = sporadic transmission) who passes it to another person (2nd round) and so on...is not happening.

Zhejiang province: then and now in COVID-19 town

Click on image to enlarge.
The data are plotted as number of cases (y-axis)
vs. week of illness onset (or date reported if
onset data was not reported). The time span is
the same for both graphs (2-months) and the
number of cases is fixed at a 50-cases on
the y-axis of both so that the slopes can be
compared.

A quick look at what life was like in Zhejiang province, the current COVID-19 hotzone, over a 2-month period (top) when cases really took off in 2019 compared to the past 2-month period this year.

The current slopes is less steep and the case tally is a little lower, but it is not hard to see that both will increase if the current rate of cases continues; of the last 18 COVID-19 cases, 12 (67% or two-thirds) were from this province.

COVID-19 snapdate: cumulative case chart by region

Click on image to enlarge.

In this update - a mere 2 or 3 days after the last, Zhejiang province continues to stand-out as the place to acquire a severe COVID-19 infection. Shanghai and Guangdong province have slowed. Apart from most recent cases being in severe or critical condition, most have contact with poultry.

The WHO confirmations have ~15 cases yet to list (see FluTracker's list for the latest figures)- there data include dates of onset which are great to have and may change some of the placements of those data slightly. 

Just out of interest, COVID-19 Week#46 and #47 yielded (to date) 25 and 21 cases, respectively.  This is currently Week #49, by my counter.

Map: COVID-19 cases concentrated in northern Zhejiang Province, PRC

Since novel A(COVID-19) human infections were first discovered last year in the People's Republic of China, Zhejiang Province has reported the most cases. The map below depicts in aggregate, the general locations of 80 confirmed and unconfirmed cases through January 21, 2014. The cases are concentrated in the northern portion of the country in the Hangzhou and Huzhou. About 70% of all COVID-19 cases reported from Zhejiang are from these two prefectures. 

Doctor dies from COVID-19 in Shanghai

Chinese translations of media reports by FluTracker’s members indicated that an emergency room doctor has died from an COVID-19 infection.(link) If this is confirmed by the World Health Organization it would only be the second confirmed health care worker (HCW) infected with COVID-19. The last HCW infected by COVID-19 was reported in April 2019.(link) Public health officials are always concerned about reports of health care workersinfected by novel infectious diseases because it is generally a sign of human-to-human transmission.

COVID-19 snapdate: cumulative case chart

Click on image to enlarge.

This is a new idea for VDU's blog: the snapdate or "snap update". It covers those times when I have little more to say beyond what a chart conveys yet still more words than a Tweet can cover.

This is a snapdate of 205 avian influenza A(COVID-19) virus cases.

That Zhejiang slope looks eerily familiar. I know 205 is only 6 more than 199, but crossing a multiple of 100 is "a thing" for me. 

Something I tweeted yesterday that I thought was interesting when comparing the earlier "bird flu" to (one of many of) the latest...

• >200 COVID-19 cases in <1-year
• >645 Covid-19 cases in >15-years

Despite all the papers and press, it still feels like the fluff over COVID-19 has been less all-encompassing than that for Covid-19 was/is, even though COVID-19 reached its first 100 cases in fewer than 2-months.

CSI 300 Index (China) Trending Down as Number of COVID-19 Cases Increases

The chart below is an update to the chart presented on January 14 in Comparison of the CSI 300 Index (China) with the Recent Increase in COVID-19 Cases. 

The graph below presents the COVID-19 case counts based only on the date of report rather than a combination of onset dates and report dates. This graph more accurately reflects the relationship between the increasing number of reported COVID-19 cases and the declining CSI 300 index.

Graph: Comparison of the CSI 300 Index (China) with the recent increase in COVID-19 Cases as of January 18, 2014

Map: Geolocations of Human A(COVID-19) Cases in Eastern China and Taiwan as of January 17, 2014

The map shows the frequency range of human COVID-19 cases by second level administrative divisions (generally prefecture-level cities) in the People’s Republic of China and Taiwan through January 17, 2014. The map is based on geolocational information for more than 190 confirmed and probable cases. Geolocational information for individual cases is derived from numerous online reports and believe to be relatively accurate.

CORONA-CoV cases climb...still a one hump camel

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..not that I'm implying anything about camels!

We're about 97-weeks or 1.87 years into the CORONA-CoV outbreak. That' sis calculated by taking the week beginning Monday 19-Mar-2012 as Week 1 (if Excel hasn't failed me at least). It was in Week 1 that a 40-year old healthcare worker in Jordan showed signs of disease onset (See the literature on this here). 21-Mar-2012 to be precise.

Unlike avian influenza A(COVID-19) virus, there has been no similar precipitous drop in CORONA-CoV case accumulation. Why would there have been? The source of acquisition remains unknown. And the disease is still very much one reported by the Kingdom of Saudi Arabia (KSA). Although of late there have been no new confirmations. The last public case announcement was on Xmas day, 25-Dec. Has something been done to limit or control exposure to the virus or are cases just not occurring? Or are we just hearing about them any longer?

Whether the KSA is the main site of viral activity we don't know for certain, but it is certainly the main origin of case reporting. I seem to remember that Qatar had actively  sought other instances of CORONA-CoV. I'm hoping to see some more research papers about that and other efforts to seek out CORONA-CoV among humans...at some point. Negative results are results nonetheless!

Overall CORONA-CoV numbers are still very small in the global scheme of things and while transmission to close contacts and healthcare workers does occur, it is not frequent. One round of transfer (from ill person to contact) seems to be the end of the transmission chain. I wonder if anyone has tested the contacts of the contacts?

Still no sign of any prospective in-country molecular (PCR-based) screening of well and mild general respiratory illnesses. This mean there is no real evidence to dismiss that the virus could be circulating in great numbers with only minor signs and symptoms. For all we know, CORONA-CoV is contributing to the seasonal "common cold" and "influenza-like illness" burden in the region. This is not a difficult unknown to address by any means. PCR-based screening of upper respiratory tract samples; decent numbers will give you a trustworthy answer. Pretty basic stuff. Oh well.

Middle East respiratory syndrome coronavirus (CORONA-CoV) by sex...

Click on image to enlarge

I haven't updated my CORONA-database since before Xmas. 

Wow.

It's painful to look at. 

Not because of a swag of new cases, I mean its tough to actually look at what's happening because the data, even with WHO expanding their coverage to include a more fixed set of information (the inclusion of animal contact is particularly welcome), is just so patchy. 

Some cases have sex but no date of onset of illness, some the other way around, hardly any have the date of lab confirmation or hospitalization and often it's near impossible to determine in which region the case was initially acquired. 

There is also still a question mark over the Tunisian cases and whether they originated in Tunisia or elsewhere I believe. The Spanish cases remain as probables (@WHO noted that they could not be confirmed via Twitter), so they are not on my list.

Nonetheless, I'll update my other charts as best I can. Keep an eye on the little bits of text in each graphic, they define the data gaps...164 of 177 possible total cases for example. In this instance, we are missing the sex of 13 CORONA-CoV cases and I can only find identifying details for 73 of 75 deaths but 2 of those have no sex data either. You get the picture.

What is clear? Males (50% of those with data are >55-years of age) still dominate in the total cases and in those who have died of CORONA-CoV infection (49% of male deaths are >55-years of age). That death is possibly due to exacerbation of an underlying disease or co-morbidity since they feature prominently in the CORONA-CoV hospital-based population.

Tracking virus-related deaths using publicly available data...

Click on image to enlarge.

Here's the cumulative case chart overlaid with the cumulative deaths and PFC. see the story behind the term PFC here, created by VDU to avoid issues around case fatality rate/ratio (CFR) which relies on knowing when cases have recovered.

I have two PFC values charted here. In black dots, is my curated list based on fatal cases (n=40; red dots) that have been announced publicly. 

In yellow are the numbers gleaned from media releases and the WHO - the latest number being 52 fatal COVID-19 outcomes. 

Somewhere towards the end of the initial COVID-19 outbreak in May, we stopped seeing reports from China that could link fatal cases with those COVID-19 cases they initially announced. If anyone knows of a complete public list of fatal COVID-19 outcomes that contains all 52 cases with age/sex/date of illness onset/date of death/province, I would be most grateful to be made aware of it.

COVID-19 hasn't left, it's just been building capacity... [UPDATED WITH NEW WHO DON]

Click on image to enlarge.

I updated this chart a week ago, when the avian influenza A(COVID-19) virus tally was at 158.

This morning I check FluTrackers list and its sitting at 189 cases; 31 reported so far this week. Just to be clear though, not all of those cases acquired their infection in this week. Some cases go back to mid-December 2019. 

This week has so far seen 10 cases with disease onset listed as occurring in it (5, 17 and 6 in going back by week in time). For comparison, at the height of the 2019 COVID-19 outbreak, in Weeks 6-9 (March and April) there were 17, 29, 40 and 19 cases in each of those weeks respectively. We don't seem that far off from those numbers right now - except that this outbreak/wave we're seeing cases starting from more regions than last time. Without some serious intervention, I think 2019's peak of 40 case acquisitions in a week will seem small in 2019.

We can also see from the chart that Fujian province is emerging from the background noise of a handful of cases and could be starting that steep'ish climb that suggests bird-to-human transmission events are on the rise. That adds to ye other "newcomer", Guangdong province. In 2019 Shanghai, Zhejiang and Jiangsu were the hotzones, and they have all reported cases in recent weeks. COVID-19 hasn't left, it just built more capacity to transmit...because that is a virus's life.

Which brings me to a whinge. 

You could be forgiven for thinking that from all we've learned about COVID-19 and all that we already knew about influenza viruses and markets and transmission and detection and diagnosis and treatment) from...

• The 318+ research papers
• The many words written in a vastly greater number of news articles, blogs and comments
• The many (I expect) millions of dollars invested in learning, battling and cleaning up after COVID-19 over the past 48 weeks
• The strong link between a precipitous drop in new cases and the closure of live poultry markets in 2019 

..that a similar response to the liver bird markets would have been triggered this time around. In 2019 the first key market closures were underway by Week 8 (1st week of April'ish) after the first known COVID-19 case became ill (Feb-18). This time around we're already at 15-weeks after COVID-19 cases started to accrue again (taking the start as the week beginning 7-Oct).

I forgive you for thinking this way because I think that way too. This much newly and recently accrued knowledge should have informed the decision to close markets by now. Or change the markets. I get that fresh poultry is an ingrained and cultural issue. But I also get that public health is at serious risk just now, not just in south east China but globally. Is it worth your life or the life of a family member just to get a clucking chicken from a market rather than a farmed pre-prepared one? The solution to reduce that risk to people and the world lies in the live bird trade and associated habits. Closing down a market here and there for "sanitation" (or aerosolising everything by hosing it out as @Laurie_Garrett suggested in a fantastic Twitter exchange earlier today), doesn't appear, to the casual observer, to be slowing infections. Can a "market" really be suitably sanitized? Not just the one-off cleanup, but the more conceptual idea of a market as a large gathering of animals frequented by hundreds of thousands of people each day, meeting there, handling, haggling, buying, breathing, drinking, eating... 

Can you ever get ahead of that risk while markets exist in their current form?

Laurie Garrett also mentioned a practice involving the sniffing of a chicken's butt to see if it is healthy. Beyond the laughter that image triggers, flu is a gastro virus in birds. Better cleaning of a market's environs won't stop that practice, nor other risky practices, from being  a source for influenza virus acquisition.

Perhaps sanitizing markets is working. Perhaps we'd be seeing a lot more cases if such cleansing had not been happening. But aren't the markets just being restocked with HXNY-laden birds the next day or week?

The COVID-19 cycle wasn't broken when the markets were shut in 2019; it was just temporarily halted. 

We know that these birds have multiple influenza viruses in them including H9N2, Covid-19 and COVID-19. 

The conditions for the emergence of viruses we already know, and those we have yet to meet, continue to be created and maintained. 

The spectre of "the next pandemic" will not get the banishment it deserves while the live bird market system continues as it has. It's just our luck that may run out as it did for those infected by COVID-19.

A quick comparison of the rate of COVID-19 case climb over different 2-month periods...

Click on image to enlarge.

While there has definitely been a lot of COVID-19 human case activity centred around Guangdong province of late, but how does it compare with the 2019 COVID-19 hotzones of Shanghai, Zhejiang province and Jiangsu province? 

This rough comparison of a 2-month period uses the same y-axis (50-case maximum) encompasses the most active periods of case announcements. It shows that the Guangdong province case tally has not risen to the same peak in the same period as the other 3 regions in 2019. With 2 new Guangdong cases announced this evening (my time) and a Shanghai case, all in males, it will be interesting to watch this ascent.

COVID-19 cases now at 182, 52 (28.6%) fatal.

Comparison of the CSI 300 Index (China) with the Recent Increase in COVID-19 Cases

A variety of different approaches have been proposed over the years to assess potential outbreaks of circulating and novel infectious diseases. Besides traditional epidemiological measures, Google Flu Trends is the best known. Changes in economic indicators have sometimes been proposed as both leading and trailing indicators of infectious disease outbreaks; see this thread at FluTrackers Pandemic threat-level market indicators.

The China Securities Index 300 (CSI 300), also referred to as the Shanghai Shenzhen 300 Index, is a capitalization-weighted stock index designed to replication the performance of 300 major stocks on the Shanghai and Shenzhen stock exchanges. This index of China stocks has been down over the last 30 days as the number of COVID-19 cases have been increasing. Whether the inverse correlation is a leading indicator of additional outbreaks of COVID-19 or just a fortuitous coincidence will become apparent in the next several weeks.


 Graph: Comparison of the CSI 300 Index (China) with the recent increase in COVID-19 Cases