Why Some People Get Worse Flu Than Others Explored in Study

Scientists believe some people suffer flu symptoms worse than others because of the first strain they encounter as a child.

The differences come down to what is known as immunological imprinting, explained the authors of a paper published in the journal PLOS Pathogens. This is where the flu subtypes a person encounters in childhood has a life-long effect on the immune system's memory and ability to protect against the bug in the future. The flu virus is highly changeable—that's why a flu shot from one year won't work the next.

On the one hand, immunological imprinting is helpful because it protects against certain strains of the flu, "but perhaps at the cost of equally strong protection against variants encountered later in life," the scientists wrote.

To carry out their study, researchers looked at data on 9,510 relatively severe cases of seasonal H1N1 and H3N2 collected by the Arizona Department of Health Services (ADHS). H1N1 and H3N2 are subtypes of the virus, which have caused serious outbreaks since the 1970s, the authors noted. By looking at the dataset, which detailed how badly the flu affected people of different ages, the scientists hoped to shine a light on the effects of childhood imprinting.

They found H1N1 and H3N2 are from different branches of the flu family tree. So, while being infected with one subtype might help to protect against the other to some extent, the body will be better equipped to fight off a strain from a group it has previously encountered, the researchers concluded.

Co-author Michael Worobey, of the Department of Ecology and Evolutionary Biology at the University of Arizona, said in a statement: "Part of your immune system's response to current infection is directed against the strain you first had as a kid, and that investment of fighting the last war appears to compromise your ability to form a fully effective immune response to the invader you encounter later."

Crunching the numbers also revealed those who had H2N2 as children did not seem to be better at combating H1N1, despite them being members of the same flu family. The team thinks this could be because the order in which we come down with subtypes could affect our ability to fight off the virus.

Lead author Katelyn Gostic, who carried out the study this research as a doctoral student at the University of California, Los Angeles, explained in a statement: "Our immune system often struggles to recognize and defend against closely related strains of seasonal flu, even though these are essentially the genetic sisters and brothers of strains that circulated just a few years ago.

"This is perplexing because our research on bird flu shows that deep in our immune memory, we have some ability to recognize and defend against the distantly related, genetic third cousins of the strains we saw as children," she said.

Worobey said: "Clearly, something compromises the immunity to strains that you see secondarily, even if they belong to the same group as your first exposure.

"The second subtype you're exposed to is not able to create an immune response that is as protective and durable as the first.

"In other words, if you were a child and had your first bout of flu in 1955, when the H1N1 but not H3N2 virus was circulating, an infection with H3N2 was much more likely to land you in the hospital than an infection with H1N1 last year, when both strains were circulating," he explained.

The authors acknowledged their study had limitations, including that relatively severe cases which involve visits to a physician are more likely to be detected and included in data than mild cases. That means they couldn't determine the relationship between imprinting and mild cases.

However, they believe their results still have implications for long-term projections of how the seasonal flu will affect older people, who are worst hit by flu-related deaths and complications. Their imprinting status will change over time as people born during when different subtypes are circulating grow older, according to the team.

They also envision the work aiding the development of flu vaccines, Gostic said.

"We hope that by studying differences in immunity against bird flus, where our immune system shows a natural ability to deploy broadly effective protection, and against seasonal flus, where our immune system seems to have bigger blind spots, we can uncover clues useful to universal influenza vaccine development," she said.