How swine flu kills

When the Illinois Department of Public Health announced Wednesday that a suburban Cook County resident had become the state’s second swine flu fatality, and the country’s 15th, the reports mentioned that the patient had suffered from “underlying conditions” and died after “complications.” But officials declined to specify the precise nature of either. Statements after the state’s first death from H1N1 influenza, reported on Monday, and those accompanying most of the country’s 15 swine flu deaths have been similarly vague.

Medill Reports spoke with Michael David, a University of Chicago epidemiologist and medical historian, who has studied the 1918 flu pandemic, about what kinds of medical conditions leave people susceptible to potentially fatal swine flu complications — and how swine flu kills when it does.

Q: We often hear that those who were hospitalized or killed by swine flu suffered from “underlying conditions” that left them susceptible them to more severe flu complications, but public health officials are mainly keeping mum about exactly which predisposing conditions we’re talking about. Do you have any insight into what kind of patients swine flu is hitting hardest?

A: Well, I don’t have any inside information. But in terms of what’s going on with this swine flu, from the news reports I’ve kept up on and updates from the [Centers for Disease Control and Prevention] and [World Health Organization], it seems like the people who are dying are the same people who would die of influenza in a regular influenza season, from the normally circulating influenza. That list of people who would die is the same list of people who are supposed to get the vaccine every year — that’s why they’re supposed to get it: people with chronic health disease, elderly people, people under the age of 2.

No one know exactly who’s at risk for this new H1N1 virus. To figure this out, they could study all of the patients who get severe enough disease to be hospitalized, because that’s many more than the number of people who have died in the U.S. You can’t really deduce anything conclusive from [a small number of] people.

The one remarkable thing about the people who are dying this time is that there haven’t been a lot of elderly people among them. That was noted in early reports from Mexico, and it raised some interest then, and that seems to be true in the United States now, too. All the people who have died whom I have heard about seem to be younger than 55.

This phenomenon may be similar to what happened in the 1918 flu pandemic, in which young adults were severely affected and many older adults were spared. One theory is that many older people may have survived the 1918 pandemic because they’d lived through the 1889-90 pandemic and may have been protected, or effectively vaccinated, by this earlier exposure.

Q: What’s so special about 1957?

A: It’s believed that H1N1 strains went largely out of circulation after 1957, when a new pandemic strain of influenza appeared and caused the pandemic of 1957-58. (A new H1N1 strain reappeared in the mid-1970s and remains in circulation today, but not the same one.) And the CDC has found that serum samples from some people who were born before 1957 indicate some level of protection from the 2009 H1N1 virus. That’s pretty interesting, and, if it is analogous to the situation in 1918, then it’s conceivable that the higher risk for serious infection or death at this time might be more common among those younger people who have risk factors for serious influenza infection.

That’s the one remarkable epidemiological generalization about those people that I know about who have died in the U.S. They’re young with other health problems.

Q: Looking at the list of predisposing conditions, there are some pretty varied vulnerabilities on there: immune deficiency, lung disease, frailty, and so on. Does swine flu kill people with different underlying conditions differently?

A: There are a few ways it can kill. People with severe underlying lung disease or people infected by a very virulent strain of influenza can die from influenza alone. Some people have lungs with a very low reserve; they’re often living on a fraction of one lung, and if that little fraction of the lung gets inflamed, then their gas exchange can become so impaired that they don’t get enough oxygen in their blood and therefore to their brains and other organs. You don’t really need to invoke any bacterial super-infection in people who die if they were already very impaired before contracting influenza.

Q: I’ve read a lot about “cytokine storms,” which is one way pandemic influenza kills healthy young adults. Cytokine storms are basically an overwhelming overreaction by our own immune systems to a novel virus, and they can lead to fatal complications. Wouldn’t a compromised immune system protect someone from those kinds of complications?

A: There are a wide variety of immune-compromised states, some caused by disease and some caused by medications. You can have a deficiency or a defect in one or more kinds of white blood cells. Some immune disorders might predispose you more to viral infection, some to bacterial infection, so it’s a little hard to generalize. Suffice it to say that no matter what kind of white blood cell line you have down, it increases your risk of dying from a viral infection like influenza.

Cytokine storm has been cited as a reason for young, otherwise healthy people dying from influenza viruses; there are many groups trying to understand how this storm can be prevented or treated effectively. It is not clear why it happens in some people and not in others.

Q: To someone who never studied advanced physiology, this all sounds a little backward. Our immune system is what kills us when we get sick?

A: With the virus, it’s not just the immune responses that is killing them. Viruses infect cells, and they kill cells. The influenza virus actually infects epithelial cells — those are cells like skin cells that line the inside of your airways. Influenza can infect those cells and then hijack the genetic machinery of the cell to make copies of itself. Eventually, it makes so many new viruses inside the cell that the cell dies, and the new viruses are released. They go on to infect and kill cells, causing inflammation and physically damaging the airways. So it’s not just the body’s inflammatory response to the virus that kills people when they die of influenza; viruses actually kill cells and damage your airways as well. It’s complicated.

Q: So we’ve got massive inflammation, the virus killing people directly — what about those secondary infections?

A: Well, those are usually severe bacterial pneumonias. There’s evidence from the 1918 pandemic and from the two subsequent pandemics that there is a symbiotic pathogenesis between influenza and the bacterium called Staphylococcus aureus, which is more commonly a cause of skin infections. There were some case reports from 1918 and case series from 1957-58 and 1968-69 of an uptick in severe and even fatal S. aureus pneumonias during influenza season. And there’s evidence they're still associated: Usually S. aureus causes less than 5 percent of pneumonias, but that number goes up when you have a bad influenza year. Also, many people who die or get very sick with pneumonia caused by S. aureus are found to have an influenza infection, as well. A lot of researchers are looking into how and why these two pathogens are linked, especially because drug-resistant strains of S. aureus are becoming more common.
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