Why a twin pandemic of coronavirus and flu may never happen

An intriguing theory may help explain why the flu and Covid-19 didn’t dominate the United States at the same time — the so-called twin epidemic that many public health experts feared.

The idea is that it wasn’t just masks, social distancing or other restrictions from the pandemic that caused the flu and other respiratory viruses to disappear as the coronavirus reigned and to re-emerge as it receded.

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

“My hunch, and my feeling based on our recent research, is that viral interference is real,” said Ellen Foxman, an immunologist at the Yale School of Medicine. “I don’t think we’re going to have flu and coronavirus spikes at the same time.”

On an individual level, she said, some people can end up infected with two or even three viruses at the same time. But on a population level, according to this theory, one virus tends to outperform the others.
Still, she warned: “The health care system can be overwhelmed well before the upper limit of circulation is reached, as the wave of the omicron showed.”

Viral interference may help explain patterns of infection seen in large populations, including those that can arise when the coronavirus becomes endemic. But the research is in its infancy, and scientists still struggle to understand how it works.

Before the coronavirus became a global threat, the flu was among the most common serious respiratory infections every year. In the 2018-2019 season, for example, it was responsible for 13 million medical consultations, 380,000 hospitalizations and 28,000 deaths.

The 2019-2020 flu season was ending before the coronavirus began to spread across the world, so it was unclear how the two viruses could influence each other. Many experts feared the viruses would collide the following year in a twin epidemic, crowding hospitals.

These concerns have not been realized. Despite a weak effort to increase flu vaccination, cases remained exceptionally low during the 2020-2021 season as the coronavirus continued to circulate, according to the Centers for Disease Control and Prevention (CDC). .

Only 0.2% of samples tested positive for flu from September to May, compared with about 30% in recent seasons, and flu hospitalizations were the lowest on record since the CDC began collecting this data in 2005.

Many experts attributed the flu-free season to masks, social distancing and restriction of movement — especially for young children and older adults, both of whom are at increased risk of contracting severe flu. Flu numbers rose a year later, in the winter of 2021-2022, when many US states waived restrictions, but the numbers were still below the pre-pandemic average.

So far this year, the US has recorded about 5 million cases, 2 million doctor visits, fewer than 65,000 hospitalizations and 5,800 flu-related deaths.

Instead, the coronavirus continued to dominate winters, far more common than influenza viruses, respiratory syncytial virus, rhinovirus, and the common cold virus.

Respiratory syncytial virus, or RSV, usually emerges in the Northern Hemisphere in September (fall) and peaks in late December to February (winter), but the pandemic has distorted its seasonal pattern. It remained low throughout 2020 and peaked in the summer of 2021 when the coronavirus plummeted to its lowest levels since the start of the pandemic.

The idea that there is some sort of interaction between viruses emerged in the 1960s, when polio vaccines, which contain weakened polioviruses, significantly reduced the number of respiratory infections. The idea gained ground in 2009: Europe seemed poised for a spike in swine flu cases later that summer, but when schools reopened rhinovirus colds somehow seemed to stop the flu epidemic.

“This led many people at the time to speculate about the idea of ​​viral interference,” Foxman said. Even in a typical year, the rhinovirus peak occurs in October or November and again in March, at either end of the flu season.

Last year, a team of researchers began studying the role of an existing immune response in fighting the flu virus. As it would be unethical to deliberately infect children with the flu, they gave children in Gambia (West Africa) 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 non-specific defenders called interferons. Children who already had high levels of interferon ended up with far fewer flu viruses 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 we saw in these children before they were vaccinated were rhinoviruses,” said 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 can also prevent coronavirus infections in adults, said Guy Boivin, a virus and infectious disease specialist at Laval University in Canada.

Recent studies have shown that flu and coronavirus co-infections are rare, and people with an active influenza infection are nearly 60% less likely to test positive for the coronavirus, Boivin noted.

“We now see an increase in flu activity in Europe and North America, and it will be interesting to see if this leads to a decrease in Sars-CoV-2 circulation in the coming weeks,” he said.

Technological advances over the past decade have made it feasible to show the biological basis of this interference. Foxman’s team used a tissue model of the human airway to show that rhinovirus infection stimulates interferons that can ward off the coronavirus.

“The protection is for a certain period of time while you have the interferon response triggered by the rhinovirus,” said Dr Pablo Murcia, a virus specialist at the MRC Center for Virus Research at the University of Glasgow, whose team found similar results.

But Murcia also discovered a twist in the viral interference theory: an attack by the coronavirus did not seem to prevent infection by other viruses. This may have something to do with the coronavirus’ ability to evade the immune system’s initial defenses, he said.

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

Silva and his colleagues collected additional data from The Gambia — which had no pandemic-related restrictions that could affect observed viral patterns — indicating that rhinovirus, flu and coronavirus peaked at different times between April 2020 and June 2021.

That data “made me a little 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 social restrictions and vaccination patterns. Therefore, the potential impact of viral interference is unlikely to become apparent until the coronavirus settles into a predictable endemic pattern, experts said.

RSV, rhinovirus and flu have coexisted for years, noted Nasia Safdar, an expert in healthcare-associated infections at the University of Wisconsin-Madison.

“Over time, that’s what will happen with this one too, he will become one of many that circulate,” Safdar said of the coronavirus. Some viruses can mitigate the effects of others, she said, but the patterns may not be immediately apparent.

Looking at the common cold coronaviruses, some researchers have predicted that Sars-CoV-2 will become a seasonal winter infection that may coincide with the flu. But the coronavirus that causes Covid-19 has already shown itself to be different from its cousins.

For example, it is rarely seen in co-infections, while 1 of the 4 common cold coronaviruses is often seen as a co-infection with the other three.

“This is the kind of interesting example that makes us hesitate to make generalizations about 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 a little virus-specific how these things occur.”

_{Translated by Luiz Roberto M. Gonçalves}