Can obesity give influenza more time to spread and make vaccines less effective?

Leading infectious disease research centers are developing a “universal flu vaccine,” hopefully within a few years. Our goal is a durable vaccine that can control an expanding range of virus strains across all age groups. But we are concerned by evidence that obese people may not be adequately protected by flu vaccines and likely to shed (release) more of the virus for longer periods.

Between 1975 and 2016, obesity rates nearly tripled worldwide, to 650 million adults. Is this one reason we are seeing more severe disease and less effective flu vaccines? We hope to answer these questions.

How much does obesity weigh?

Let’s clarify our definition of obese: Many people reserve that word to describe someone with a weight or body-mass problem severe enough to make public accommodations inaccessible.

Is an adult who weighs 175 pounds obese?

That’s the low end of obesity for an average-height woman (5’4”). The threshold is around 205 pounds for average-height men (5’9”). You can calculate body mass index (BMI) with this tool to determine if an adult is underweight, healthy weight, overweight, or is one of three classes of obesity.

Connecting obesity with flu severity

A recent influenza field study, funded in part by the National Institute of Health (NIH) and the St. Jude Children’s Research Hospital Center of Excellence for Influenza Research and Surveillance (CEIRS), monitored the effect of obesity on the duration of viral transmission within households. Dr. Aubree Gordon (University of Michigan) and her research team observed that obese adults displaying influenza symptoms carried transmittable virus in their mucous 42% longer than non-obese adults. Ironically, this trend was even worse among people who did not appear to be sick. Infected obese adults with no flu symptoms—or one minor symptom—could transmit the virus twice as long as non-obese adults with similar symptoms.

Why is St. Jude researching influenza?

There was some good news from that field study: Obese children and teens did not appear to be able to shed or transmit influenza for any longer than non-obese children. They were probably still facing a higher risk of catching the flu, and catching it worse. This brings up a common question:

Since when is a children’s hospital, famous for cancer research, studying influenza?

We have been doing this a lot longer than you might think.

Last year marked the 100th anniversary of the cataclysmic 1918 “Spanish flu” pandemic. For more than half of that century, St. Jude has been investigating influenza viruses. This work has always been important for our cancer patients because cancer treatments suppress their immune systems and put them at risk for infectious diseases.

Tracing the problem to the lungs

The St. Jude Department of Infectious Diseases has pursued extensive laboratory studies on the obesity-influenza connection, building on important discoveries from the World Health Organization’s investigation of the 2009 H1N1 flu pandemic.

Our data suggests that influenza virus may spread deeper and faster into overweight patients’ lungs, and the deeper it goes, the more likely they are to develop pneumonia.

To get a better idea of how fast the flu viruses are replicating, a graduate student in my lab, Rebekah (Bekah) Honce, looked at lung cell samples from obese donors. She noticed that these cells had a problem sensing influenza viruses. They were not releasing antiviral interferons or releasing them late. And when the cells did sense the virus, they seemed to overreact, which can increase inflammation.

Bekah also found that flu viruses in obese samples replicated faster and required lower viral concentrations to be able to infect cells. Once infected, these vulnerable cells take longer to clear the virus, and they take longer to heal membranes wounded by viruses, which increases the risk of secondary bacterial lung infections.

What we don’t know…yet

Does flu immunity improve after an obese patient loses weight? The answer to this will actually answer a number of questions, but designing a viable study for it will be challenging.

What about obese patients who regularly exercise without losing much weight? We are wondering if exercise—getting them metabolically healthy—is enough to reduce the flu severity. If that’s the case, the problem is not the obesity itself, but what it's doing to your body.

Does obesity that is not caused by a diet-exercise imbalance still affect viral responses? We are fairly sure that it doesn’t matter if the obesity is caused mostly by genetic/epigenetic marks or by over-eating.

Studying obesity requires studying the obese

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, put a priority on supporting the “moon-shot” development of a universal flu vaccine. But the growing population of obese patients poses an experimental challenge. Our studies show that vaccinated obese people and models lose their protective responses faster—making them more likely to get infected even when vaccinated.

But that doesn’t mean you shouldn’t get your flu shot! Even if the shot doesn’t protect you from getting sick, it may protect you from developing severe disease like pneumonia and new studies suggest it may protect you from having a heart attack or stroke.

We are concerned that clinical trials to test new universal flu vaccines will likely be conducted only with “healthy” people. Obesity would normally disqualify those human subjects from the trials. We need to think more about how we can study and protect this population, especially since it's becoming the majority of our population.