Why the coronavirus and flu “dundemia” may never happen

An intriguing theory may help explain why influenza and Covid-19 never swept the nation at once – the so-called twin that many public health experts feared.

The idea is that it was not just masks, social distancing, or other pandemic restrictions that caused the flu and other respiratory viruses to fade while the coronavirus reigned and revive when it withdrew.

Rather, exposure to a respiratory virus can put the body’s immune defenses on high alert, preventing other intruders from entering the airways. This biological phenomenon, called viral interference, can limit the amount of respiratory virus circulating in a region at any one time.

“My perception, and my perception based on our recent research, is that the viral intervention is real,” said Dr. Ellen Foxman, an immunologist at Yale Medical School. “I don’t think we will see the peak of the flu and the coronavirus at the same time.

At the individual level, she said, there may be people who end up infected with two or even three viruses at once. But at the population level, according to this theory, one virus tends to outpace the others.

However, she warned: “The health system can be overloaded long before the upper limit of circulation is reached, as shown by the Omicron wave.

Viral interference may help explain the patterns of infection observed in large populations, including those that may occur when the coronavirus becomes endemic. But research is in its early days, and scientists are still struggling to figure out how it works.

Before the coronavirus became a global threat, influenza was among the most common severe respiratory infections each year. In the 2018-2019 season, for example, the flu was responsible for this 13 million medical visits, 380,000 hospitalizations and 28 thousand death cases.

The 2019-2020 flu season ended before the coronavirus began to rage around the world, so it was unclear how the two viruses could affect each other. Many experts feared the viruses would collide next year in stormy, congested hospitals.

These worries were not realized. Despite weak efforts to increase flu vaccinations, cases remain unusually low throughout the flu season 2020-2021 as the coronavirus continues to circulate, according to the Centers for Disease Control and Prevention.

Only 0.2% of the samples tested positive for influenza from September to May, up from about 30% in recent seasons, and flu hospitalizations are the lowest since the agency began collecting these data in 2005.

Many experts attribute the flu-free season to masks, social distancing and limited movement, especially for young children and the elderly, both of whom are at the highest risk of severe flu. The number of influenza rose a year later, in the 2021-2022 season, when many states dropped the restrictions, but the numbers were still lower than the pre-pandemic average.

So far this year, the nation has registered about five million cases, two million medical visits and less than 65,000 hospitalizations and 5,800 flu-related deaths.

Instead, the coronavirus continues to dominate in winter, much more common than influenza, respiratory syncytial virus, rhinovirus, and cold viruses.

The respiratory syncytial virus, or RSV, usually appears in September and peaks in late December to February, but the pandemic has distorted its seasonal pattern. It remained low throughout 2020 and peaked in the summer of 2021, when the coronavirus fell to its lowest levels since the pandemic began.

The idea that there is something like an interaction between viruses first appeared in the 1960s, when polio vaccinations that contained attenuated poliovirus significantly reduced the number of respiratory infections. The idea took new ground in 2009: Europe seemed poised to jump on swine flu cases later this summer, but when schools reopened, rhinovirus colds seemed to somehow end the flu epidemic.

“It made a lot of people at the time speculate about this idea of ​​viral intervention,” Dr. Foxman said. Even in a typical year, the rhinovirus peaks in October or November and then again in March, at both ends of the flu season.

Last year, a team of researchers set out to study the role of the existing immune response in preventing the flu virus. As it would be unethical to deliberately infect children with the flu, they gave children in the Gambia a vaccine with a weakened strain of the virus.

Virus infection triggers a complex cascade of immune responses, but the first defense comes from a set of nonspecific defenders called interferons. Children who already had high levels of interferon were found to have much less flu virus in their bodies than those with lower levels of interferon, the team found.

The results show that previous viral infections have prepared children’s immune systems to fight the flu virus. “Most of the viruses we saw in these children before we vaccinated them were rhinoviruses,” said Dr Tushan 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 are more likely to have respiratory infections than adults are less likely to be infected with the coronavirus. Influenza can also prevent coronavirus infections in adults, said Dr. Guy Boyvin, a virologist and infectious disease specialist at Laval University in Canada.

Recent studies show that co-infections with influenza and coronavirus are rare, and those with active influenza infection are nearly 60 percent less likely to test positive for coronavirus, he said.

“We are now seeing an increase in influenza activity in Europe and North America, and it will be interesting to see if this will reduce the circulation of SARS-COV-2 over the next few weeks,” he said.

Advances in technology over the last decade have made it possible to demonstrate the biological basis of this intervention. Dr. Foxman’s team used a model of human airway tissue to show that rhinovirus infection stimulates interferons, which can then repel the coronavirus.

“Protection is transient for a period of time until you have this rhinovirus-induced interferon response,” said Pablo Murcia, a virologist at the University of Glasgow’s MRC Virus Research Center, whose team found similar results.

But Dr. Murcia also found a distortion in the theory of viral interference: the fight against the coronavirus does not seem to prevent infection with other viruses. This may have something to do with how well the coronavirus is able to evade the immune system’s initial defenses, he said.

“Compared to the flu, it tends to activate these antiviral interferons less,” Dr. de Silva said of the coronavirus. This finding suggests that in a population, it may matter which virus appears first.

Dr de Silva and his colleagues gathered additional data from The Gambia – which had no pandemic-related restrictions that could affect the viral patterns they observed – showing that rhinovirus, influenza and coronavirus peaked at different levels. time between April 2020 and June 2021

These data “made me a little more convinced that intervention could play a role,” he said.

However, the behavior of viruses can be strongly influenced by their rapid evolution, as well as societal restrictions and vaccination patterns. So the potential impact of viral intervention is unlikely to become apparent until the coronavirus is established in a predictable endemic model, experts said.

RSV, rhinovirus and influenza have coexisted for years, said Dr. Nasia Safdar, an expert on health-related infections at the University of Wisconsin-Madison.

“Eventually this will happen to this one as well – he will be one of many circulating,” Dr. Safdar said of the coronavirus. Some viruses may weaken the effects of others, she said, but the patterns may not be obvious.

Looking at coronaviruses with the common cold, some researchers predict that SARS-CoV-2 will become a seasonal winter infection that may coincide with the flu. But the pandemic coronavirus has already turned out to be different from its cousins.

For example, it is rarely seen in coinfections, while one of the four common colds coronavirus is often considered a coinfection with the other three.

“This is a kind of interesting example that makes one hesitant to summarize many viruses,” said Jeffrey Townsend, a biostatistician at the Yale School of Public Health who studies the coronavirus and its seasonality. “It seems to be somewhat specific to the virus how these things happen.”

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