Severe obesity makes it almost five times more likely that adults infected with the H1N1 pandemic influenza virus will be ill enough to be hospitalized, and also more likely that they will die under certain conditions, according to new research by the Centers for Disease Control and Prevention (CDC).

The finding quantifies for the first time the frequent observation, made during clinical care and confirmed by surveillance data, that obesity has played a greater-than-expected role in H1N1 illnesses and deaths. Writing in the online medical journal Public Library of Science ONE (PLoS ONE), the researchers say that obesity appears to play such a powerful role that it exerts an effect independent of any underlying chronic conditions that patients may have.

The researchers were not able to say how obesity exerted that effect, but an unrelated piece of research may provide some insight. Using a study in mice, University of North Carolina researchers report in the Journal of Immunology that obesity caused by overfeeding seems to impair the immune system’s ability to create the immunologic memory that allows the body to recognize and respond to flu infections.

The CDC study used data on hospitalizations and deaths gathered by state health departments early in the pandemic, between April and July 2009. As a control, the researchers compared the cases to a healthy cohort, using data from the National Health and Nutrition Examination Survey (NHANES), a nationwide representative survey.

For each group, the researchers calculated body mass index (BMI), a ratio of height to weight that is used as a universal measure of under- or overweight. They also recorded whether group members suffered from at least some of the chronic medical conditions—cardiovascular disease, pulmonary disease, liver disease, cancer, and diabetes—that federal health authorities have previously defined as playing a role in severe flu.

Pregnant women were not included in the study, even though they have also been observed to be at higher risk of H1N1 illness and death, because BMI-related definitions of overweight do not apply to them.

The results show that obesity appears to play a definite role in flu illness and death, though calculating the degree of its influence was limited by the quality of the data about some of the groups. Obesity had no effect on the illnesses and deaths of teenagers and children younger than 20, who were more likely to be very ill and die if they were underweight rather than overweight.

Among adults, morbid obesity—the highest category of overweight, defined as a BMI of 40 or more—played a significant role in the risk of developing a flu infection serious enough to require hospitalization. Those with chronic medical conditions were 4.9 times more likely to be hospitalized; those who did not have such conditions were 4.7 times more likely.

But the analysis of flu deaths did not show such a consistent effect of morbid obesity. In some runs of the data, the association between obesity and flu death was strongest for those without chronic underlying conditions; in other analyses, the strongest association was among those who died and did have chronic conditions. Oliver Morgan, PhD, a CDC epidemiologist and the first author of the study, said that lack of consistency was likely due to poorer-quality data on both BMI and underlying conditions among those who died, rather than to any lack of effect exerted by obesity.

The CDC researchers were careful to say that the specific role played by obesity in severe disease from flu has not been much studied. It is well-accepted in medicine, though, that obesity complicates severe illness, causing longer stays and greater need for mechanical ventilation in intensive care and predisposing obese patients to wound infections, sepsis, and pneumonia.

The North Carolina study, though preliminary, suggests one possible reason why. The researchers used a mild lab-adapted flu virus to experimentally infect both lean mice and mice that had been fattened by overfeeding. They then infected them a second time with a more lethal flu virus. One fourth of the obese mice, but none of the lean mice used as controls, died as a result of the second infection.

On pathologic exam, the obese mice showed higher rates of lung inflammation along with much higher amounts of flu virus in their lung tissue than the lean mice did. Analysis showed that the obese mice had produced much lower numbers of influenza-specific memory T cells, which permit the immune system to recognize and mount an attack against subsequent flu infections, and the T cells that were present were less effective in mounting a defense against the flu viruses.

The authors say the findings are likely to have greater significance given the worldwide prevalence of obesity alongside the persistence of flu as a serious seasonal infection. Among other things, the findings may suggest that obese people may be less likely to mount adequate immune responses after flu vaccination.

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Maryn McKenna

Morgan OW, Bramley A, Fowlkes A, et al. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1) disease. PLoS ONE 2010 Mar 15;5(3):e9694

Karlsson EA, Sheridan PA, Beck MA. Diet-induced obesity impairs the T cell memory response to influenza virus infection. J Immunol 2010 Mar 15;184(6):3127-33