Yes, Swine Flu Is Worse Than Seasonal Influenza

Although most cases of swine-origin H1N1 influenza have been ‘mild’, half of those hospitalized with severe illness have none of the pre-existing conditions that might complicate an influenza infection: asthma, heart disease, hepatitis, immunosuppresion, pregnancy, among others.

A new study explains why. Itoh et al. demonstrate swine-origin H1N1, now pandemic, to be intrinsically more virulent than previously assumed. Indeed, the infection expresses characteristics of some of the more deadly influenzas, including highly pathogenic H5N1, the bird flu virus.

Itoh and colleagues tracked the pathogenesis of the new H1N1 infection. They conducted experiments on mice, ferrets, pigs and macaques, comparing the effects of swine-origin H1N1 and recent strains of seasonal H1N1. The team discovered,

  • Mice suffered greater mortality from swine-origin H1N1 than seasonal H1N1. The dose required to kill 50% of the mice exposed was a power of magnitude less for swine-origin H1N1 than its seasonal counterparts.
  • Swine-origin H1N1 replicated more efficiently in the mice’s lungs, causing bronchitis and alveolitis, with viral antigen openly present. It also elicited greater production of host cytokines that have been previously associated with greater morbidity and mortality in other influenza infections.
  • Macaques infected with swine-origin H1N1 underwent greater increases in temperature than those infected with seasonal H1N1. Swine-origin H1N1-infected macaques also suffered a greater tissue range infected and more severe lung pathogenesis. Their lungs hosted inflammatory infiltrates, exudates clogging the alveolar sacs, severe thickening of the alveolar walls, and pneumocytes of types 1 and 2. Type 2 pneumocytes have also been reported in infections of highly pathogenic H5N1.
  • Ferrets—a good small-animal model of human influenza infection—showed no difference in changes in temperature and body weight. However, swine-origin H1N1 replicated to greater concentrations in the trachea and lungs. Ferrets infected with swine-origin H1N1 also expressed greater bronchopneumonia and viral antigen.
  • Virulence alone isn’t our sole concern. It’s virulence and transmissibility in tandem that’s keeping scientists up at night. The new H1N1’s pandemicity shows the virus by definition transmissible. But for experimental completeness, Itoh et al. ran exposure tests on ferrets. The animals were infected at the same rates when exposed to swine-origin H1N1 as when exposed to seasonal strains of H1N1.
  • The experiments also spoke to the difficulties in identifying the geographic origins of the virus. Miniature pigs infected with swine-origin H1N1 suffered no clinical symptoms even as the virus replicated in the pigs’ respiratory organs. The asymptomatic infection may offer another explanation for the dearth of reportable outbreaks in possible source swine populations in Mexico or elsewhere.

Finally, Itoh et al. exposed the new H1N1 to influenza antibodies circulating in humans of different age groups. Does exposure to previous H1N1 strains, back to the 1918-1919 pandemic, protect humans from the worst of the new influenza? Only patients born before 1920 expressed the antibodies that could neutralize swine-origin H1N1. The new H1N1 appears to be expressing epitopes similar to those of the 1918 H1N1, epitopes to which very few of us have the antibodies needed to neutralize.

This last result raises two important points. First, seasonal H1N1 influenzas may be in fundamental ways different from their 1918 ancestors. For those more technically inclined, the level of polymerase CpG may be one explanation. Second, swine-origin H1N1 may have been able to revisit molecular solutions from a pandemic 90 years ago now that a large enough cohort of naïve humans has emerged. Although influenzas–with life cycles of only a few days–evolve from infection to infection, the constraints on influenza evolution may extend back a hundred years. In influenza time that’s the equivalent of a geological eon.

So, yes, swine-origin H1N1 2009, as transmissible as any human influenza, is worse than seasonal H1N1. Indeed, as WHO reports, in some patients it may be as bad as highly pathogenic H5N1, the bird flu virus that has killed over 60% of those reported infected. And very few of us—except those infected before 1920 and since April—have the antibodies needed to neutralize it.

Here’s hoping this autumn’s flu season, when many more are expected to be infected, doesn’t include a worsening virulence, as occurred in 1918. With a phenotype from a bygone era, H1N1 may be evolving into the viral Tyrannosaurus it once was.

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