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Monday, April 27, 2009

A [cytokine] storm seems to be brewing

I try to leave the medical stuff to the the professionals.  After all, they went to school and actually studied the science behind most of the stuff that scares the bajeezus out of laymen (like yours truly).  But today I am still too scared to sit still... so I'm going to blather on about yesterday's topic.

First a working definition for the medically challenged:

Cytokine Storm

A cytokine storm (pronounced 'sigh-toe-kine') is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.

The primary symptoms of a cytokine storm are high fever, swelling and redness, extreme fatigue, and nausea.

When the immune system is fighting pathogens, cytokines signal immune cells such as T-cells and macrophages to travel to the site of infection. In addition, cytokines activate those cells, stimulating them to produce more cytokines. Normally, this feedback loop is kept in check by the body. However, in some instances, the reaction becomes uncontrolled, and too many immune cells are activated in a single place. The precise reason for this is not entirely understood but may be caused by an exaggerated response when the immune system encounters a new and highly pathogenic invader.

Cytokine storms have potential to do significant damage to body tissues and organs.  If a cytokine storm occurs in the lungs, for example, fluids and immune cells such as macrophages may accumulate and eventually block off the airways, potentially resulting in death


So here's what has me worried: 

In recent years scientists have exhumed the frozen bodies of victims of the 1918 flu pandemic who were buried in Alaska's permafrost and successfully extracted live virus samples from their lungs for study.   

One of the things they have discovered from studying these long-frozen samples of the 1918 flu virus is that the reason it was most deadly among healthy adults (rather than infants and the elderly as one would assume), is that it seems to have set off a cytokine storm in the bodies of those who contracted it. 

The stronger the immune system, the more violent and destructive the storm. 

An infant or elderly person's immune system isn't strong enough to mount a sufficiently violent insurrection against a pathogen, but a healthy adult... that's another story.  And if you look at who is dying from the Mexican swine flu, it is healthy adults... not infants, not the elderly and not the immuno-compromised.

I also want to expand on something that I have been noticing in the way the media is treating this story:

The mainstream media is first and foremost a marketplace.  They are all competing for market-share and will do pretty much anything to woo readers/listeners/viewers from the competition.  For this reason when a story comes up that can be exploited to elicit a strong emotional response (e.g. fear, anger, joy, etc.) it is usually flogged mercilessly with screaming headlines and breathless commentary.

However, if you pay attention to what is going on today in the media, everyone (and I do mean everyone) is carrying the story... yet they are all being extremely careful not to overplay it.  If anything, they seem to be down-playing the story; and hiding behind canned recommendations from the CDC and government health representatives rather than offering their own commentary. 

It's almost as if they are saying, "This is not a drill... this is the real thing, so we need everyone to stay very calm and wait for the people in charge to tell us what to do".

Lastly, I want to share my own personal theory about the current mortality patterns, which is based on so little scientific knowledge that it probably wouldn't even be taken seriously among avid fans of television medical dramas:

I think that the reason we are seeing a much higher mortality rate in Mexico than in the US is a serendipitous result of our abuse of antibiotics and other modern medical miracles here in the first world.  Our immune systems are so over-protected and pampered by our tendency to run to prescription and over-the counter medicines at the first sign of discomfort, that they never get much of a work-out.

By comparison, people living in developing countries and the third world are less reliant on drugs to protect them, so their immune systems tend to be much more robust than ours.  What this means (to me) is that if this strain of flu has the ability to set of a cytokine storm in the bodies of the people who contract it, it stands to reason that the ones who will die are those with the strongest immune systems.

Living, as I do, in a country where doctors are extremely careful about the use of anti-biotics, and where a large portion of the population are immigrants from developing countries and the third world... I am very frightened right now. 

I hope against hope that I am completely wrong about this.

Posted by David Bogner on April 27, 2009 | Permalink


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Just my two cents: The spanish flu ravaged in 1918, right at the end of WWI. I'd figure that many young adult males (at least in Europe) did not have much of an immune system at the time, having spent the past few years in trenches shooting toxic gas at each other...

Posted by: Carsten | Apr 27, 2009 10:37:33 AM

Carsten... As I've pointed out above, the people that research has shown were most likely to have died from the 1918 flu were healthy adults with strong immune systems. Just as an aside, the armies of WWI were using chemical agents against one another, but those who survived years in the trenches of Europe were likely to have had extremely strong immune systems. Those who didn't have good immune protection died from infections caused by wounds and 'trench foot'.

Posted by: treppenwitz | Apr 27, 2009 11:27:36 AM

according to xkcd ( http://xkcd.com/574/ ) you should spend the next few weeks drunk and sleep deprived in order to weaken your immune system

Posted by: Shimon | Apr 27, 2009 12:28:33 PM

What worries me most at present is the way official authorities are treating the problem here in France. People who arrive from Mexico just seem to go home as if they arrived from any country. The health instructions are for people who go there not those who come from there.

Posted by: Ilana-Davita | Apr 27, 2009 12:38:19 PM

Scary, I hope it doesn't get to this part of the world.

Posted by: Rami | Apr 27, 2009 1:16:21 PM


Now I am truly torn between:
1) pointing and giggling at my germ-o-phobic spouse, and
2) running out to buy surgical masks for everyone I know

Good. Job. Honey.

Posted by: zahava | Apr 27, 2009 1:25:20 PM

As far as I can see there are no data so far which would allow for such farreaching theories.


Posted by: Ruth | Apr 27, 2009 2:57:07 PM

I don't know about that analysis at the end. Granted I agree with you that we are a nation of pill poppers especially here in the states, what with our antibacterial soaps, etc, but regardless, we are doing pretty well in the mortality rate dept. True they dont have all these niceties in the 3rd world, but the mortality rate is higher and they die younger. I don't know if I can say you are accurate in your theory.

Posted by: J K | Apr 27, 2009 3:02:36 PM

Shimon... I don't need anyone's advice to do that! :-)

Ilana-Davita ... This is the same group of French health officials that sat by while a bunch of elderly people died during a severe heat wave a year or two ago, no?

Rami... Me too, my friend.

zahava... my work here is done. ;-)

Ruth ... The Miami Herald article you linked to doesn't compare apples to apples. They are comparing those in Mexico who died from the disease to those in the US who survived. Ironically their statements about all the Mexican fatalities being between 20-40 and the fact that those who survived in the US are both old and young, supports my theory that this strain of flu is attacking healthy adults with strong immune systems.

J K ... I'm not sure you understood my theory. I suggested that the mortality rate in the US would be much lower than in the developing and third world BECASUE our immune systems are not used to doing the heavy lifting.

Posted by: treppenwitz | Apr 27, 2009 3:47:44 PM

David, I don't follow the logic of your last three paragraphs. According to your theory, it is the third world people, who, having fought off infections without aid of antibiotics, have robust immune systems, who are at the greatest risk. People who had recourse to antibiotics have less explosive immune systems. Unless you're worried because as a former sailor, you've overcome who knows how many horrible diseases....

Posted by: Barzilai | Apr 27, 2009 4:34:01 PM

Barzilai ... my logic eludes you because you are operating under the mistaken assumption that I am worried for my own personal safety. That is not the case. I received so many immunizations during my years in the navy that my immune system has barely had to get out of bed during my adult life, much less work out. But my children have rarely taken antibiotics during their lives and I live in a country full of Israelis... many of whom come from third world and developing countries. My concern is not for myself, but rather what I (as a father and an Israeli) stand to lose.

Posted by: treppenwitz | Apr 27, 2009 4:41:30 PM

I'm unconvinced that this is anywhere near the 'big deal' that the media is making it out to be. This does not seem to be particularly infectious and is being contained pretty well. Neuraminidase inhibitors seem to treat it effectively, which is likely to sharply contain the spread of the disease. There are a total of twenty confirmed cases in the US, which means that any speculation about population-wide effects - including cytokine storms and our susceptibility or lack thereof - is largely silly.

I think you're overreacting. Influenza is one of the biggest concerns for the CDC and similar organizations because of previous pandemics. While this means that in principle we should be concerned as well, it also means that all of their efforts for decades have been focused on limiting the spread and mortality of various influenza strains. I suspect that the ~5-10% mortality seen thus far in Mexico is because it took them until this past week to realize what kind of disease they were treating (and I have doubts about the quality of Mexico's healthcare system and their stocks of neuraminidase inhibitors,which the US - and presumably Israel - has in sufficient supply).

I wouldn't sweat it - at the best, just improve your normal hygeine (which everyone should do regardless) by handwashing, taking care in personal contact, covering your mouth and nose when sneezing/coughing, etc. These are normal precautions and aren't any major concern. Let the pandemic specialists deal with the problem.

Remember SARS? Fatality rate of 10%, nearly 10,000 cases across half the world, concerns about cytokine storms, fears of a global pandemic, etc, etc. At the end of the day, it was contained and there were very few deaths among those who were treated in the Western world - and that was without adequate antivirals or much of anything else. This infection was caught much earlier (mostly due to the CDC) and is being aggressively contained.

Posted by: matlabfreak | Apr 27, 2009 4:42:38 PM

Interesting theory, but I still don't know if you're serious. I've become skeptical about everything. If a pandemic did sweep the earth of 1/3 of all humans, would you more likely attribute it to the wrath of God, collective freewill, individual freewill or unknown forces? Just be on the safe side and wash your hands more often.

Posted by: David Bailey | Apr 27, 2009 5:58:33 PM

I think the whole world is waiting for the proverbial second shoe to drop (who knows what was the first?); it could be some crazy Mexican Swine Flu or a madman who tries to unload a nuclear bomb.

Either way, we're doomed, I tell you.

Posted by: Baila | Apr 27, 2009 6:16:52 PM

David & friends,

I am cautiously concerned -- and I live in California, a lot closer to Mexico than you.

One surmise about the situation in Mexico is that the fatalities have to do with a much high viral load than the average infection. Plus the mortality rate seems high possibly because the actual number of infections have been seriously under-counted.

Posted by: Liz Ditz | Apr 27, 2009 7:22:50 PM

Call me what you will, but I am just not worried. Perhaps concerned, but not worried. I interact with people who are in out of Mexico virtually every day.

See no evil, fear no evil. At least I hope that is how it works. ;)

Seriously, I'll keep washing my hands and paying attention to hygiene, but beyond that...

Posted by: Jack | Apr 27, 2009 7:45:38 PM

This is the same group of French health officials that sat by while a bunch of elderly people died during a severe heat wave a year or two ago, no?
More or less, yes.

Posted by: Ilana-Davita | Apr 27, 2009 9:10:57 PM


There have not been any US fatalities as far as I know. There is not sufficient data on the number of infections in Mexico. I am not sure that all the fatalities in Mexico can be ascertained to be victims of the flu.

This is my point, you lack the data to jump to any conclusions. I am not trying to falsify your theory, I am just pointing out that it is much to early to form any such theory.

Posted by: Ruth | Apr 27, 2009 9:14:58 PM

Israel is neither the US nor Mexico. Climate and medical care differ. Although Israel is kinda like California...

I wouldn't go greet any Aliyah flights this year unless I had close family on board, though.

Flu kills when there isn't modern medical care available, as there wasn't in 1918. Israel has good modern medical care and a citizenry that will follow the rules, if any are issued. And flu season is about to end this year, giving us working time before next season.

Traffic deaths will greatly outnumber flu deaths for a long time. So drive carefully and wash your hands.

Posted by: Fred | Apr 27, 2009 10:03:01 PM

We have children in isolation in New Zealand after returning from a school trip to Mexico. They are exhibiting the symptoms of Swine Flu.

Posted by: Noa | Apr 27, 2009 10:32:32 PM

Fred - you're wrong about the flu. It's killed around 17-52k per year; the CDC estimate for the 1990s is approximately 36k on average (I believe it's something like the 7th or 8th leading cause of death in the US); traffic deaths are of the same order (around 41k for 2007). In Israel, the number of traffic deaths was 382-437 for the last year (according to the CBS, not including the territories, which add about 30). So we're talking 400-450 deaths, roughly (for comparison, that's about half the fatality rate of the US, to give you some perspective on those people who complain about traffic safety in Israel). They don't provide influenza statistics, since you need large numbers and resources to estimate the influenza death toll; I suspect no one has done it for Israel. I'd guess it's more than the US ratio, since Israel has lower flu vaccination rates, though that's all a big guess. So that would mean that there are either comparable or MORE flu deaths than traffic deaths in Israel.

Posted by: matlabfreak | Apr 27, 2009 11:10:57 PM

correction: the traffic deaths were 382-437 for the last FOUR years... duh, I can't write.

Posted by: matlabfreak | Apr 27, 2009 11:11:58 PM

Just for completion's sake: The WHO cites approximately 800 deaths in Israel from respiratory infections in 2002, though they don't give data for how many are pneumonia and how many are flu (normally something like 1/3 pneumonia and 2/3 flu, at least by reference to US statistics IIRC). So there are definitely more flu-associated deaths than traffic-associated deaths.

Posted by: matlabfreak | Apr 27, 2009 11:25:45 PM

Did somebody up there just say that "Israel has a citizenry that will follow the rules???"

Now that's funny.

Posted by: Baila | Apr 27, 2009 11:59:29 PM

I have no idea if the 1918 pandemic cytokine link is correct, however, I agree that the tone of the U.S. government's announcement was so eerily calm as to be frightening. I think the U.S. government is a couple of steps away from panic. I am not normally alarmist, but there are some non-medical factors in play.

The flu vaccine this year apparently does not cover swine flu, so there is likely no immunized population. There is no permanent head of the Department of Health and Human Services, the FDA or the CDC. They have trotted out the the Secretary of Homeland Security! They are asking the population not to demand Tamiflu from their doctors because of fear of resistance. Today the U.S. recommended limiting travel to Mexico.

This is what will happen if this is the real thing. Cities will stop working. Mexico City has come to a dead stop. People will not report to work to avoid contact. The transportation system will come to a halt and borders will selectively close.

Maybe nothing will happen, but I think you are correct to be wary.

Posted by: lrg | Apr 28, 2009 12:17:52 AM

I find it interesting that Tamiflu is supposed to be effective against this strain of Flu.It was not effective against the major flu strains in the US in the just concluded flu season.Could it be that this virus is so new,that it hasn`t had time to mutate,and thus defend itself against Tamiflu? If we overuse Tamiflu,won`t it soon damage its effectiveness against this strain?

Posted by: ED | Apr 28, 2009 4:14:08 AM

Irg - of COURSE the flu shot didn't include this strain of flu, that's how the flu shot is made up. They try to predict what strain of flu is going to be prevalent nearly a year before the flu season to give us time to synthesize the doses necessary. It's a mixture of very sophisticated epidemiological models, careful research, and a lot of guesswork. That's why some years the flu shot is more effective than others. When something that simply can't be predicted - like a mutation/recombination event causing a cross-species jump that results in a new, communicable influenza A virus.

Neither do we need a head to the CDC, FDA, or DHHS for the important people to get things done. All of the people who actually do stuff at those agencies (rather than setting overall policy) are not political appointees.

Nothing is going to happen like the doomsayers are predicting. People are currently still going to work in Mexico (though schools - one of the major ways to trasfer infection - are currently closed), and I suspect they will continue to do so. The flu can and has been effectively treated and contained. The only way 'cities will shut down' is if people panic precisely because they're listening to crazy stuff in the media rather than thinking.

ED - Tamiflu is the most famous of a class of drugs that are transition state inhibitors of neuraminidase (the "N" part of the H1N1 designation for the current flu; it's one of the two proteins that coat the virus; the inhibitors stop the virus from exiting an infected cell and continuing the infectious cycle). As with any such drugs, minor changes in the structure of neuraminidase will stop a particular drug from working, though the drugs in development always try to target highly conserved parts of the structure (i.e. if the virus NEEDS a specific structure to function, they can't change it much without losing their infectivity - so it's a good drug target). So we have seen some resistance developed to currently used flu drugs such as Tamiflu - just as with antibiotics. It has been used very sparingly by doctors in recognition of this reality. *shrugs* Just a matter of time - we develop antivirals, the viruses mutate, we develop more.

Don't panic. Trust me, I work with a lot of the people who figure this stuff out.

Posted by: matlabfreak | Apr 28, 2009 6:24:01 AM

David, we are going to be in Efrat for Yom HaAtzmaut for a mangal with friends. Can I come over and breathe on you? ;)

Posted by: westbankmama | Apr 28, 2009 7:03:12 AM

1. America's no-fatalities seems to be due more to actively pursueing treatment, VS sloppy work in Mexico.

2. I suspect that the high death rate in middle-aged adults might be because this group was the easiest to get infected (those are the ones out on the streets, amoungst others.....

Posted by: rickismom | Apr 28, 2009 7:22:45 AM

...and in the US, those who go to Mexico for spring trips are young.

Posted by: matlabfreak | Apr 28, 2009 7:30:09 AM

Though I wouldn't say "not to worry," remember that the Chinese did an admirable job of controlling SARS. Well, it did get to 37 countries, but it could have been a lot worse. It killed fewer than a thousand people and about eight thousand people contracted it. It all depends on how the government deals with it. The part that scares me is how rapidly the current swine flu is spreading from state to state.

Posted by: Diane Gordon | Apr 28, 2009 7:48:49 AM

Actually, the Chinese did a piss-poor job of dealing with SARS. With adequate treatment, no one should have died - it was only when WESTERN health organizations started noticing there was a problem - and only after severe pressure on China - did they take serious steps to treat it as an epidemic. If something like that had happened in the US, the fatality count (and probably infection count) would have been significantly lower.

Posted by: matlabfreak | Apr 28, 2009 9:04:43 AM

Hi Trep,
A team of construction-missionaries from our church just returned from working at a Mexican orphanage for the last week.

My 17 year old son came down with the flu last night and is home from school today feeling awful.


I'm calm, but like Zahava, I'm a bit torn. ::Thinking of buying the masks NOW::

Posted by: Maya | Apr 28, 2009 6:42:09 PM

Medicine in Israel is very sophisticated. I would not worry about this flu, there.

Here in the big apple, we are calm. Mike Bloomberg is our fantastic mayor and he is always on the ball. As far as we are concerned, here, life is going on as usual.

Keep in mind, the bigger the media frenzy on any subject, the better the ratings......and swine flu is no different.

It does seem that we will find out that cytokine storm is the reason why Mexicans have died, but not anyone else, from any other country, who has swine flu.

Posted by: Joyce Hays | Apr 29, 2009 12:05:41 AM

Hey, Trep

without reading the comments, I wanted to say I liked your thinking in this post. Nice work, very cogent.

I'm still not worried at all, myself, but I think you outlined a very nice potential avenue of valid worry to pursue.

I'm going to put it in my back pocket for later.

Posted by: Wry Mouth | Apr 29, 2009 8:23:08 AM

I'm with you.

I never get sick. I can't remember the last time I had a cold -- it's been at least three years, and I haven't taken antibiotics in probably ten. I just have a naturally strong immune system (and being a fan of very spicy food helps).

And now I'm sick. And I just came back from California. I wouldn't say I'm nervous, but if I start running a fever, I might get nervous.

Posted by: Tanya | Apr 29, 2009 11:17:10 PM

"level 5"... siiiigh...

Posted by: Wry Mouth | Apr 30, 2009 4:07:17 AM

Your Alaskan researchers contradict most earlier well documented studies that show that most people who died in the 1918 flu epidemic died of secondary strep. There IS something alarming about this new strain and that is that there are strong indications that it was manufactured in a lab. (It's happened twice before). This makes it a biological warfare item..no, not done by the Mexican govt., but they may have inadvertantly been chosen as the launching pad. Read www.mercola.com

Posted by: marcia | May 1, 2009 9:22:52 AM

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