An intriguing theory may help explain why the flu and Covid-19 never gripped the nation simultaneously — the so-called twindemic that many public health experts had feared.
The idea is that it wasn’t just masks, social distancing or other pandemic restrictions that caused flu and other respiratory viruses to fade while the coronavirus reigned, and to resurge as it receded.
Rather, exposure to one respiratory virus may put the body’s immune defenses on high alert, barring other intruders from gaining entry into the airways. This biological phenomenon, called viral interference, may cap the amount of respiratory virus circulating in a region at any given time.
“My gut feeling, and my feeling based on our recent research, is that viral interference is real,” said Dr. Ellen Foxman, an immunologist at the Yale School of Medicine. “I don’t think we’re going to see the flu and the coronavirus peak at the same time.”
At an individual level, she said, there may be some people who end up infected with two or even three viruses at the same time. But at a population level, according to this theory, one virus tends to edge out the others.
Still, she cautioned, “The health care system can become overburdened well before the upper limit of circulation is reached, as the Omicron wave has shown.”
Viral interference may help explain patterns of infection seen in large populations, including those that may arise as the coronavirus becomes endemic. But the research is in its early days, and scientists are still struggling to understand how it works.
Before the coronavirus became a global threat, influenza was the among the most common severe respiratory infections each year. In the 2018-2019 season, for example, the flu was responsible for 13 million medical visits, 380,000 hospitalizations and 28,000 deaths.
The 2019-2020 flu season was winding down before the coronavirus began to rage through the world, so it was unclear how the two viruses might be influencing each other. Many experts feared that the viruses would collide the next year in a twindemic, swamping hospitals.
Those worries were not realized. Despite a weak effort to ramp up flu vaccinations, cases remained unusually low throughout the 2020-2021 flu season, as the coronavirus continued to circulate, according to the Centers for Disease Control and Prevention.
Only 0.2 percent of samples tested positive for influenza from September to May, compared with about 30 percent in recent seasons, and hospitalizations for flu were the lowest on record since the agency began collecting this data in 2005.
Many experts attributed the flu-free season to masks, social distancing and restricted movement, especially of young children and older adults, both of whom are at the highest risk for severe flu. Flu numbers did tick upward a year later, in the 2021-2022 season, when many states had dispensed with restrictions, but the figures were still lower than the prepandemic average.
So far this year, the nation has recorded about five million cases, two million medical visits, and fewer than 65,000 hospitalizations and 5,800 deaths related to the flu.
Instead, the coronavirus has continued to dominate the winters, much more common than the flu, respiratory syncytial virus, rhinovirus and common cold viruses.
The respiratory syncytial virus, or R.S.V., usually surfaces in September and peaks in late December to February, but the pandemic distorted its seasonal pattern. It lay low through all of 2020 and peaked in the summer of 2021 — when the coronavirus had plummeted to its lowest levels since the pandemic’s beginning.
The notion of that there is a sort of interplay between viruses first emerged in the 1960s, when vaccinations for polio, which contain weakened poliovirus, significantly cut the number of respiratory infections. The idea gained new ground in 2009: Europe seemed poised for a surge in swine flu cases late that summer, but when schools reopened, rhinovirus colds seemed somehow to interrupt the flu epidemic.
“That prompted a lot of people at that time to speculate about this idea of viral interference,” Dr. Foxman said. Even in a typical year, the rhinovirus peaks in October or November and then again in March, on either end of the influenza season.
Last year, one team of researchers set out to study the role of an existing immune response in fending off the flu virus. Because it would be unethical to deliberately infect children with the flu, they gave children in Gambia a vaccine with a weakened strain of the virus.
Infection with viruses sets off a complex cascade of immune responses, but the very first defense comes from a set of nonspecific defenders called interferons. Children who already had high levels of interferon ended up with much less flu virus in their bodies than those with lower levels of interferon, the team found.
The findings suggested that previous viral infections primed the children’s immune systems to fight the flu virus. “Most of the viruses that we saw in these kids before giving the vaccine were rhinoviruses,” said Dr. Thushan de Silva, an infectious disease specialist at the University of Sheffield in England, who led the study.
This dynamic may partly explain why children, who tend to have more respiratory infections than adults, seem less likely to become infected with the coronavirus. The flu may also prevent coronavirus infections in adults, said Dr. Guy Boivin, a virologist and infectious disease specialist at Laval University in Canada.
Recent studies have shown that co-infections of flu and the coronavirus are rare, and those with an active influenza infection were nearly 60 percent less likely to test positive for the coronavirus, he noted.
“Now we see a rise in flu activity in Europe and North America, and it will be interesting to see if it leads to a decreased in SARS-COV-2 circulation in the next few weeks,” he said.
Advances in technology over the past decade have made it feasible to show the biological basis of this interference. Dr. Foxman’s team used a model of human airway tissue to show that rhinovirus infection stimulates interferons that can then fend off the coronavirus.
“The protection is transient for a certain period of time while you have that interferon response triggered by rhinovirus,” said Pablo Murcia, a virologist at the MRC Center for Virus Research at the University of Glasgow, whose team found similar results.
But Dr. Murcia also discovered a kink in the viral interference theory: A bout with the coronavirus did not seem to prevent infection with other viruses. That may have something to do with how adept the coronavirus is at evading the immune system’s initial defenses, he said.
“Compared to influenza, it tends to activate these antiviral interferons less,” Dr. de Silva said of the coronavirus. That finding suggests that in a given population, it may matter which virus appears first.
Dr. de Silva and his colleagues have gathered additional data from Gambia — which had no pandemic-related restrictions that might have affected the viral patterns they were observing — indicating that rhinovirus, influenza and the coronavirus all peaked at different times between April 2020 and June 2021.
That data has “made me a bit more convinced that interference could play a role,” he said.
Still, the behavior of viruses can be greatly influenced by their rapid evolution, and by societal restrictions and vaccination patterns. So the potential impact of viral interference is unlikely to become apparent till the coronavirus settles into a predictable endemic pattern, experts said.
R.S.V., rhinovirus and flu have coexisted for years, noted Dr. Nasia Safdar, an expert on health-care-associated infections at the University of Wisconsin—Madison.
“Eventually that’s what will happen with this one, too — it will become one of many that circulate,” Dr. Safdar said of the coronavirus. Some viruses may attenuate the effects of others, she said, but the patterns may not be readily apparent.
Looking at common-cold coronaviruses, some researchers have predicted that SARS-CoV-2 will become a seasonal winter infection that may well coincide the flu. But the pandemic coronavirus has already shown itself to be different from its cousins.
For example, it is rarely seen in co-infections, while one of the four common-cold coronaviruses is frequently seen as a co-infection with the other three.
“That’s the kind of interesting example that makes one sort of hesitate to make generalizations across multiple viruses,” said Jeffrey Townsend, a biostatistician at the Yale School of Public Health who has studied the coronavirus and its seasonality. “It seems to be somewhat virus-specific how these things occur.”