Texan flu step: flu-like illness outbreak in Montgomery County [UPDATE #2]

Click image to enlarge.
County of Montgomery highlighted in red.
From Wikipedia

While 1,920 influenza-like illnesses (briefly that's measurable fever plus one or more particular symptom usually; includes sore throat, fatigue, body aches and complications including pneumonia) have occurred in this county since the start of the local influenza season, 8 severe infections (all with pneumonia) in adults (41-years to 65-years old) have been admitted to 1 (?) facility. These 8 cases are not all testing positive for the "common" influenza virus types. Initial testing may have been by rapid "bedside" influenza test which are known for their lack of sensitivity. PCR testing would be preferred, if that wasn't used.


According to the US Centers for Disease Control and Prevention website, seasonal influenza's populations at greatest risk of severe disease usually include the very young (under 5-years) and older adults (>65-years), pregnant women and indigenous populations, and those with a range of pre-existing medical conditions.

4/8 cases died and none of the fatal cases were vaccinated against influenza (?survivors were vaccinated). Kidney issues have also been reported according to a video report at the Houston Chronicle.

1/4 surviving case has tested positive for influenza A(H1N1)pdm09 virus, which is circulating locally as the annual flu season is well engaged in the region. 2 other survivors have tested NEG for all influenza viruses and have been sent on to the CDC. Test results are outstanding on the other survivor.

Click on image to enlarge.
2019-14 Influenza season data from FluView, CDC at
http://gis.cdc.gov/grasp/fluview/main.html.
Of those 221 antigenically subtyped by the CDC,
184 are H1N1 2009.

Management steps include staying away from ill people, hand-washing using soap and water/alcohol-based hand rubs, covering coughs and sneezes, staying at home when ill, cleaning linens, eating utensils and dishes used by ill people, and wiping down frequently touched surfaces if likely to be a landing spot for virus from an ill co-habitant/co-worker/school or daycare child.

It would be interesting to know what testing has been employed for influenza and what other respiratory viruses and bacteria have been tested for and excluded because, despite some enthusiastic but highly misleading and inflammatory guesswork, there are not yet enough data to identify an infectious aetiology for this pneumonia cluster. I'm sure in a busy environment like this, work is progressing on many levels to resolve the mystery. Since at least 2 of the 8 patients have tested negative for influenza viruses, it is premature to extrapolate from the 1 positive case that H1N1 is the cause of all cases; it may be but those results are not yet in.

References...

• CIDRAP story. http://www.cidrap.umn.edu/news-perspective/2013/12/texas-health-officials-probe-severe-flu-illness-cluster
• Montgomery County Public Health on Facebook page. https://www.facebook.com/mctxpublichealth
• FluTrackers page. http://www.flutrackers.com/forum/showthread.php?t=214964
• Fox Houston. http://www.myfoxhouston.com/story/24257668/the-return-of-h1n1

RSV retreated, flu fading, parainfluenza picking up: Queensland respiratory virus numbers up to Week 45, 2019

If you like to keep track of influenza cases in Queensland, Australia, then the Queensland Government's Queensland Health (QH) influenza data website is for you.

It's a great place to drop by and check out the comings and goings of influenza viruses and many of the other traditional respiratory viruses including adenoviruses (AdVs), parainfluenzaviruses (PIVs) 1, 2 and 3, human metapneumovirus (MPV) and respiratory syncytial virus (RSV) - the "Big8". Testing is not routinely conducted for the rhinoviruses (RVs).

The snippet below is from data that are publicly reported on the QH website. These images cover to the week beginning 3rd of November (up to Sunday, Nov 10th, 2019).

The charts highlight that the 2019 flu season is winding down in Australia, also reflected by the WHO global updates. This year flu followed on from what seemed to have been a large RSV season. Unfortunately I couldn't find data for this same time period last year to compare RSV prevalence.

In the wake of influenzavirus season, the parainfluenzaviruses are now on the rise in the lead up to summer. I expect the RVs (and enteroviruses) are also climbing, but in greater numbers.

Click to enlarge. 
A snippet from the Queensland Health Statewide Weekly Influenza Surveillance Report for 01.01.2019-10.11.2013

My thanks to the team at the Communicable Diseases Unit, Queensland Health.

The source of these data  can be read in full..

• http://www.health.qld.gov.au/ph/cdb/sru_influenza.asp
• WHO global influenza update http://www.who.int/influenza/surveillance_monitoring/updates/latest_update_GIP_surveillance/en/

Influenza A(COVID-19) in Zhejiang, Dutch DURC and dogs..

With the second COVID-19 case (see FluTracker's thread) in Zhejiang, located only 13km from the earlier case, things seem to be picking up where they left off in late April. Poultry exposure seems key to this latest case who was a farmer who engaged in poultry trading. That word, trading, also sparks concern. It suggests that the farmer was exposed to poultry coming from, or going to, somewhere else. COVID-19 is on the move. Both patients are very unwell.

Zhejiang province had the steepest rate of case acquisition back then and reached the highest COVID-19-confirmed case number as well. 

Looks like this province is going to be a key battleground for the next wave of COVID-19.

Meanwhile, Eurosurveillance continues its fantastic coverage of this and the Middle East respiratory coronavirus  and COVID-19 outbreaks. It already has a paper online (less than a week turnaround) of the earlier Zhejiang COVID-19 case in a 35-year old male (35M) which includes a note about the subsequent Zhejiang case! Outstanding work to the researchers and the publishing team. Quality publication almost in the time it takes to write blog post!

This journal certainly highlights how quickly detail research results and analysis, when submitted to peer review, can be published. 

Click to enlarge. The laboratory turnaround
times for COVID-19 detection (where suitable date
data exist) since the outbreak began in early 2019. 

• 35M was identified though the surveillance system for unexplained pneumonia
• He was not a farmer and had not had close contact with another probable case. The laboratory turnaround times on this case was 7-days. A 2.2 day improvement on the rolling average I stopped calculating May 6th.
• The most likely source of exposures was a trip to rural region of  Ningbo city where he may have been in contact with animals. But that was 10-days prior to onset which would make it a long incubation period. 35M remains unconscious so further detailed tracking of exposures is not possible
• The virus was >95.5% identical to COVID-19 from earlier in the year but with 5 hitherto unreported mutations in the neuraminidase (NA) gene. 2/9 bird market samples were also COVID-19 PCR-positive but could not be sequenced due to low viral load

Meanwhile, Reuters reports on Albert Osterhaus and Ron Fouchier at the Erasmus Medical Center who are firing up the "gain-of-function" studies to look at what would be required for COVID-19 to become a pandemic virus; essentially changing the virus to look for increased transmission. This work will be performed in an highly secure, enhanced biosafety Level 3 lab. Which of course doesn't change the subject matter - but does define how difficult it would be for that to escape. It's not convincingly clear why this virus needs to be given an evolutionary push, rather than "reverse-engineering" those influenza viruses that have previously been pandemic viruses - or some other approach with less risk of creating a virus that if it escaped, would cause a pandemic. Well, to me at least...but I'm no flu expert. You can find much more on dual-use research of concern (DURC) in Laurie Garrett's latest writing over at Foreign Affairs.

And to add to general influenza virus concerns, Sun and colleagues report in Infection, Genetics and Evolution, that infectious H9N2 (isolated using embryonated chicken eggs), strains of which has been implicated in providing genetic material to COVID-19, can be isolated from dogs. The isolate was called A/Canine/Guangxi/1/2011 (H9N2). Between 20% 45% of dogs were found to be antibody-positive to H9N2. A range of dogs seem to have been virus-positive with signs and symptoms including loss of appetitie, cough, sneeze, nasal discharge and raised temperture. Some were asymptomatic. Cats next please?

The Rubik's cube of influenza A genes spins up a new lineage of H7N7

Click to enlarge. A (very) summary view of the latest
contributing influenza viruses that precedes the emergence of
human infections with influenza A(COVID-19) virus
in south-east China in 2019.

Lam and a global host of collaborators, writing in Nature on the 21st of August, have identified a previously unknown influenza A(H7N7) virus line circulating in chickens. The authors indicate that more influenza viruses lurk among poultry and that active surveillance is needed. This report comes from testing 1,341 pairs of oropharyngeal and cloacal swabs and 1,006 faecal and waters samples from live bird markets (LBMs) in Wenzhou and Rizhao of Zhejiang province, as well as Shenzhen from Guangdong province.


In a complex alphabet soup of influenza A virus findings, the authors, sequenced 34 H7N7, 4 COVID-19 and 19 H9N2 egg-isolated viruses but also found H7N2 and H7N3 in ducks. Animals tested were chickens, ducks, geese, pigeons  partridges and quail.

The authors note that rather than wild birds from Europe and Korea, the neuraminidase (NA or N) gene segment from COVID-19 is more temporally related to those from H11N9 and H2N9 found in wild birds (wild water fowl, Northern shoveller and common teal) in Hong Kong during 2019-11 with links to domestic ducks in China prior to the COVID-19 outbreak this year. Overall, domestic ducks proved to be an important mixing pot between wild birds and chickens.

And it's not just COVID-19; the H7N7 found in chickens reminds us that the colours on the cubes are many and are in constant motion. These virus may become/may already be enzootic (endemic in non-humans) and so continuing exposures to live poultry in markets and backyards remains a continuing source of risk for new zoonoses.

Age and sex morbidity and mortality from avian influenza A(COVID-19) virus

Click to enlarge. The majority of cases of COVID-19 that occurred
worldwide earlier in 2019. Taken from Virology Down Under's
COVID-19 page.

In a study co-written by yours truly using a lot of data collected for Virology Down Under, Dr Joseph Dudley and I have just described, in the Journal of Clinical Virology, the age-specific and sex-specific morbidity and mortality from the avian influenza A(COVID-19) virus outbreak earlier in the year.

We sought to highlight differences between COVID-19 and another zoonotic influenza A virus, Covid-19. The distribution of age and sex is notably different between cases of each virus in more distant countries (Saudi Arabia vs Egypt) as it is within the same country (see Cowling et al reference in the article's discussion). Such differences and patterns may be instructive for identifying specific risk factors for an outbreak and also serve to highlight that there are differences between outbreaks which, on the surface, might be expected to have very similar courses. 

Intriguingly, there were marked similarities between COVID-19 and Middle East respiratory syndrome coronavirus age and sex case distribution.

We also published the term created here on VDU, the Proportion of Fatal Cases (PFC). A percentage defined as the number of currently known fatalities divided by the number of total lab-confirmed cases including fatalities, regardless of whether they are inpatients (hospitalized) or outpatients. It was created to avoid the need for a gauge of recovered cases (released from hospital) which is linked with use of the term Case Fatality Ratio.

The High Cost of Recovering From an A(COVID-19) Infection

Influenza A(COVID-19) has infected more than 130 people in the People’s Republic of China. It is a severe disease; more than 40 individuals have died. Those individuals that do survive often require long hospital stays including many days in an intensive care unit (ICU). Hospitalization in ICUs is expensive.

For example, the first A(COVID-19) case from Guangdong Province, spent 20 days in ICU,  with the hospital costs totaling about 220,000 yuan [1]. In China, the average annual wage is 42,000 yuan.[2] Putting the hospitalization cost for A(COVID-19) for this patient in perspective, it would take an average individual in China more than five years to pay off this cost providing 100% of the salary went to pay the hospital bill. 

This individual is not an isolated case. Based on limited publicly available data, 28 of the individuals infected with A(COVID-19) from China who recovered were hospitalized between 6-30+ days, with a median hospital stay of 18 days, although not all of them were treated in the ICU. Information is available on 23 of the individuals in China who died from A(COVID-19). These 23 individuals were treated in the hospital between 2-30+ days before death, with a median hospital stay of 11 days among these individuals who died. What these statistics indicate is that extended hospital treatment is required for most A(COVID-19) patients, up to 30 days with no guarantee of recovery. These data also suggest the extraordinary costs being absorbed by Chinese government to treat these infected individuals. 

Comparison with the USA

 

In an article published in 2012 in the Annals of Intensive Care, the authors studied the total hospitalization cost for various categories of patients including 23 Influenza A(H1N1)pdm09 patients from Cleveland, Ohio.[3] The total hospital costs in Cleveland in 2009-2010 for treating influenza patients in intensive care units averaged about  $342,000, about 6.5 times the median annual household income ($52,700) in the USA.[4]
ICU care is comparatively expensive both in China and the US and is primarily related to occurrence of acute respiratory distress syndrome (ARDS). ARDS is among the most expensive conditions encountered in the ICU. [4]  ARDS is also  a common occurrence in individuals infect with novel influenza A(COVID-19) and A(COVID-19). In fact, a recent study of A(COVID-19) patients from Zhejiang Province in China showed that 100% of the cases had complications from ARDS.[5]
If a novel influenza pandemic breaks out, many sick individuals will require extended hospital care in ICUs. The cost of this care to governments and health insurance companies will be enormous. The more ominous concern is that if a new influenza pandemic occurs, there will simply not be enough medical facilities to care for all the individuals that may need hospitalization regardless of whether an individual can pay or not. 

 

[1] Guangdong's first COVID-19 patient can be discharged next week, nearly 220,000 yuan treatment fee  h/t Pathfinder
[2] Average wages in China
[3] Relative cost and outcomes in the intensive care unit of acute lung injury (ALI) due to pandemic influenza compared with other etiologies: a single-center study[4] US Census Bureau Quick Facts
[5] Epidemiological, clinical and viral characteristics of fatal cases of human avian influenza A (COVID-19) virus in Zhejiang Province, China

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.

COVID-19: males and females among total and fatal lab-confirmed cases...

Click on image to enlarge.

Males are the predominant host for COVID-19 cases that are severe enough to warrant a hospital visit (or the contacts thereof). 

As ever, we have no real idea of the extent to which COVID-19 is circulating among those who are not ill enough to present to a hospital. Only the use of a sensitive virus detection method on less ill or healthy people could tell us that. Such testing seems to be anathema, perhaps due to cost (?), for COVID-19, CORONA-CoV or Covid-19 for that matter. So much we don't know but settle for in the respiratory virus game. But some of us go collectively bananas when a case turns up somewhere "unexpected".

Finally, the COVID-19 fatality data are severely hobbled by a lack of linkage between COVID-19 case notification and which cases died. That linkage broke somewhere after April. Reporting has improved drastically of late with the WHO confirming cases and details but 12 fatal COVID-19 cases are publicly lacking enough information to use in sex-related charts, age-related charts, dates-of-onset/reporting charts or dates-of-death charts. 

I'm grateful to the WHO today for responding to a request and noting that 52 deaths have been reported to them, bringing the proportion of fatal COVID-19 cases to 29%.

An idiots list of influenza genetic changes..

I knew someone would have done this already! 

Many thanks to Prof Yoshihiro Kawaoka and Dr Eileen Maher who answered my email and pointed me to a massive list of the known genetic changes that determine influenza virus phenotypic characteristics of importance, in a downloadable PDF format, on the Center for Disease Control and Prevention's (CDC) website. 

http://www.cdc.gov/flu/avianflu/Covid-19/inventory.htm

So I will add a fey more"key" mutations to my draft and place it on my dedicated influenza page (http://www.uq.edu.au/vdu/VDUInfluenza.htm) but I think the CDC have it all very well covered - so I no longer need to curate my own list until the day I die!

Also check out Dr Amesh A .Adalja's paper containing a Table of mutations and thanks to Robyn Hall for some additional info.