This year's flu season has been especially harsh, driven in part by the rapid spread of a new variant known as subclade K. As cases rise, a newly released study offers surprising insight into how influenza spreads and how people may better protect themselves from getting sick.
To better understand how flu moves from person to person, researchers from the University of Maryland Schools of Public Health and Engineering in College Park and the School of Medicine in Baltimore designed an unusual experiment. College students who were already infected with influenza were placed in a hotel room with healthy middle-aged adult volunteers. Despite close contact, none of the healthy participants became infected.
"At this time of year, it seems like everyone is catching the flu virus. And yet our study showed no transmission -- what does this say about how flu spreads and how to stop outbreaks?" said Dr. Donald Milton, professor at SPH's Department of Global, Environmental and Occupational Health and a global infectious disease aerobiology expert who was among the first to identify how to stop the spread of COVID-19.
Why the Flu Did Not Spread
The study, published on January 7 in PLOS Pathogens, represents the first controlled clinical trial to closely examine airborne flu transmission between people who were naturally infected, rather than intentionally infected in a laboratory, and people who were not infected. Milton and his colleague Dr. Jianyu Lai explored several reasons why none of the volunteers became ill.
"Our data suggests key things that increase the likelihood of flu transmission -- coughing is a major one," said Dr. Jianyu Lai, post-doctoral research scientist, who led data analysis and report writing for the team.
Although the infected students carried high levels of virus in their noses, Lai explained that they rarely coughed. As a result, only small amounts of virus were released into the air.
Ventilation also played a key role. "The other important factor is ventilation and air movement. The air in our study room was continually mixed rapidly by a heater and dehumidifier and so the small amounts of virus in the air were diluted," Lai said.
Age may have been another protective factor. According to Lai, middle-aged adults tend to be less vulnerable to influenza than younger adults, which likely contributed to the absence of infections.
What This Means for Flu Prevention
Many scientists believe that airborne transmission is a major driver of flu spread. However, Milton emphasized that changes to global infection-control guidelines require strong evidence from randomized clinical trials like this one. The research team is continuing its work to better understand how flu spreads through inhalation and under what conditions that transmission is most likely.
The lack of transmission observed in this study provides valuable clues about how people can reduce their risk during flu season.
"Being up close, face-to-face with other people indoors where the air isn't moving much seems to be the most risky thing -- and it's something we all tend to do a lot. Our results suggest that portable air purifiers that stir up the air as well as clean it could be a big help. But if you are really close and someone is coughing, the best way to stay safe is to wear a mask, especially the N95," said Milton.
Inside the Flu Experiment
The research took place on a quarantined floor of a Baltimore-area hotel and included five participants with confirmed influenza symptoms and 11 healthy volunteers. The study was conducted across two groups during 2023 and 2024. A similar quarantine design had been used in earlier research, along with specialized testing of exhaled breath developed by Milton and his colleagues.
Participants lived on the isolated hotel floor for two weeks and followed daily routines designed to mimic real-life social interactions. These included casual conversations and physical activities such as yoga, stretching, and dancing. Infected participants also handled shared items like a pen, tablet computer, and microphone, which were then passed around the group.
Researchers closely tracked symptoms and collected daily nasal swabs, saliva samples, and blood samples to monitor infection and antibody development. They measured viral exposure both in the air participants breathed and in the room itself. Exhaled breath samples were collected daily using the Gesundheit II machine, invented by Milton and colleagues at Harvard T.H. Chan School of Public Health.
Why Flu Research Still Matters
Finding better ways to limit flu outbreaks remains a major public health priority, according to Milton. Influenza continues to place a heavy burden on health systems worldwide. Each year, up to 1 billion people globally become infected with seasonal flu. In the United States alone this season, there have already been at least 7.5 million cases, leading to 81,000 hospitalizations and more than 3,000 deaths.
The study included contributions from researchers at UMD's interdisciplinary Public Health Aerobiology Lab, including Kristen Coleman, Yi Esparza, Filbert Hong, Isabel Sierra Maldonado, Kathleen McPhaul and S.H. Sheldon Tai, as well as collaborators from the UMD Department of Mechanical Engineering, the University of Maryland School of Medicine, Icahn School of Medicine at Mount Sinai in New York, the University of Hong Kong, and the University of Michigan, Ann Arbor.
Funding for the research came from the NIAID Cooperative agreement U19 grant (5U19AI162130), the University of Maryland Baltimore Institute for Clinical and Translational Research (ICTR), the University of Maryland Strategic Partnership: MPowering the State (MPower), and gifts from The Flu Lab and Balvi Filantropic Fund.
