What would it take to build a flu forecast?
The researchers think the cancer patients’ flu evolution predated the virus’s global changes by so many years in part because these four people had such long infections. With a standard, weeklong infection, the virus has less of a chance to evolve because only a few hundred viruses out of the millions present in one person’s body are transmitted to the next infected person, Xue said.
Those short infections and that transmission bottleneck lead to a “stop-and-start process of evolution,” she said. In effect, the virus’ evolution may be accelerated in patients with longer infections.
But it’s also possible that favorable viral mutations appear in individual people years before they are able to take over the entire world’s population of viruses. And that possibility hints that individual infections could, one day, be used to forecast flu’s global evolution.
Predicting the mutations that take over the world would improve vaccine design, Xue said. Currently, researchers associated with the World Health Organization pick flu strains to include in each year’s vaccine about nine months before the next flu season starts, allowing sufficient time for vaccine production. It’s a sophisticated and well-researched process, but it doesn’t always capture the correct strains for a given flu season. Methods to better predict which viral strains will dominate each year could result in more effective vaccines.
The researchers' next step is to understand whether they can see these early hints of global viral evolution in people with average-length infections. That will take a lot more than just four infections, Xue said. But the data is already out there, ready to be analyzed. Through the WHO’s monitoring efforts, thousands of flu samples are taken around the world every year, and, increasingly, those samples are analyzed with the same deep-sequencing methods that would allow such detailed analyses.
A unique group of four
The samples used in the study don’t reflect the typical flu infection — but they do underscore the importance of better understanding the virus. Influenza can be deadly for transplant patients. Because their immune systems can take up to a year to rebound after the procedure, those who undergo transplants are especially susceptible to easily transmitted — and often mild — infections like the common cold and flu.
Normally, doctors do not bother tracking and analyzing colds and flu in healthy people. But at Fred Hutch’s clinical care partner, Seattle Cancer Care Alliance, and many other cancer centers, patients who come down with a respiratory virus are followed very carefully because of the danger these infections pose. Colds and flu can lead to pneumonia and even death in many transplant patients.
In the original study, the patient volunteers, who all received transplants at SCCA, donated weekly swabs from their nose and mouth for as long as their infections lasted. With the volunteers’ consent, extra material from those samples was stored in Fred Hutch freezers — in case it could be useful for future research.
“We’re incredibly grateful that these people who are undergoing really difficult treatments are still willing to participate in studies,” Xue said. “The original study was conducted 10 years ago, and now that we have new methods, some of these original samples are bearing fruit in a way that we could never have imagined.”