Over the last 24 hours, I’ve received a few comments and even more emails asking about or discussing the possibility of a “cytokine storm” triggered by the H1N1 swine flu reassortant. Is this what’s happening in the cases from Mexico? Discussion after the jump…
Let me begin with a bit of background on what’s meant by a “cytokine storm.” In response to infection, the body has a number of ways to fight back against the invading microbe. Cytokines are one part of this defense. These are molecules produced by a number of different types of cells in response to infection that act as signals to other cells in the body–telling them to divide, or to produce certain proteins, or to cease their production. They assist, basically, in orchestrating portions of the immune response. A “cytokine storm” occurs when this regulation goes haywire–the very molecules that are supposed to be protecting the body end up causing it harm by responding too strongly to the infection. (Note that this is quite over-simplified; the cytokine response itself is incompletely understood, and other players in addition to cytokines are also involved).
This is where the “young and healthy” issue comes into play. Children have immune responses that are still developing, while the elderly tend to lose some immune function with the aging process. However, the middle age group–roughly age 15 to 50, give or take–tend to have an active, vigorous immune response upon invasion by a pathogen. Most of the time, this keeps us relatively free of disease from microbes, but some organisms tend to trigger this type of hyper-response that actually ends up harming the host–in some cases, fatally. This is what we’ve seen in some cases of H5N1 infection, and what’s been induced in mouse models with the 1918 H1N1 strain.
So, are we seeing this with the reassortant swine H1N1 virus, or should we expect to find that it causes this? Is this why reportedly many of the deaths to date are in the “young and healthy”? Right now, we simply don’t know. As I mentioned yesterday, the data from Mexico (from media reports, at least) are sparse, and only a handful of cases have been confirmed to be caused by the novel swine flu virus. This makes attempts to extrapolate to any larger trends a risky and imprecise endeavor, and the old adage certainly applies: garbage in, garbage out. So right now (again, from media-reported data), we don’t know for sure that there really is a higher number of “young and healthy” dying from this virus than we would expect to see–so whether this trend even exists is a big question mark.
However, even if we do see an excess of deaths in that middle age group, there could be other reasons besides the “cytokine storm.” Perhaps this group has exposures that have made them more likely to contract the virus than other age groups, so the greater number of deaths is simply a result of a greater number of exposed individuals. Perhaps they were less likely to have been vaccinated in recent years, meaning they had no cross-protective immunity. (This also is a big question mark, as we don’t know, even in vaccinated individuals, that any immunity to human H1N1 viruses would confer any protection). Perhaps they’ve simply been more likely to be noticed in this outbreak, and thus their cases have received more attention and were more likely to have been worked up (as far as obtaining a culture, etc.) than those in the typical influenza risk groups. There are just too many unknowns right now to address these questions, but certainly they will be investigated as more surveillance data is collected.
Additionally, other clues may come from additional analyses of the virus itself. In H5N1 and the 1918 H1N1 strains, we know there are certain mutations in both of them that have been associated with increased virulence. When all the genes of the novel swine virus are sequenced, the presence or absence of these mutations can be determined, suggesting it may or may not be likely to induce the type of cytokine response that has been associated with the highly virulent strains. Expect an information overload when researchers have more of a chance to examine the virus itself in greater depth…
[UPDATED: The Washington Post has an article up discussing the infection in young adults in Mexico.]