Something is disrupting the normal seasonal streams of cold and flu viruses. They were down to a trickle during the early part of the Covid pandemic only to burst through human populations this year. Some public health experts have called it “tripledemia,” but it could even be described as quadrupledemia.
In the northern hemisphere, the flu began to emerge in October, months before its normal season. This year has also seen a strong early rise in two other viruses, RSV (respiratory syncytial virus) and adenovirus. These normally cause colds, but RSV can be dangerous for young children and has recently led to overcrowding in children’s hospitals. Adenovirus is also usually mild, but this month there were reports of the virus putting college athletes in ICUs, and it has been implicated in clusters of dangerous hepatitis cases in children.
Because right now? The easy answer is that wearing masks for more than two years reduced the incidence of these viruses and subsequently people lost their immunity, something the popular press has dubbed “immunity debt.” But that’s unlikely to be the whole story. The circulation patterns of different viruses appear to be influencing each other in ways that are not fully understood, said Michael Osterholm, director of the Center for Infectious Disease Research and Policy and host of a Covid podcast.
“When multiple respiratory viruses are circulating in any given season, one of them will dominate for reasons we don’t understand,” he said on the podcast. “Something is going on there that cannot be attributed to personal protection alone. [or] distancing.”
Some other researchers made a similar observation this week in Science. “Influenza and other respiratory viruses and SARS-CoV-2 just don’t get along very well,” virologist Richard Webby told the magazine. Or as epidemiologist Ben Cowling of the University of Hong Kong put it: “One virus tends to intimidate others.”
That means viral interference could be a bigger factor than immunity debt.
Osterholm notes that the same suppression of other viruses occurred in 2009 when the H1N1 flu broke out. “For the first time in years, we didn’t see other influenza strains like H3N2 or any RSV activity. It just disappeared,” he said. “It can’t be because of the mitigation, because we didn’t do mitigation.”
He said he also doubts that mitigation was as effective against RSV and flu because it wasn’t terribly effective against Covid: More than 75% of children had been infected as of February 2022. Osterholm has pointed to previous research showing that while N95 masks work, there is much less evidence behind the types of loose-fitting cloth masks common in school settings (although school closures likely disrupted the course of other seasonal viruses).
Viral interference might offer a fuller explanation. Our innate immune system includes disease-fighting substances called interferons, which can protect people infected with one virus from contracting another. That may be why, as a large study from the University of Glasgow published in 2019 showed, cold viruses plunge as flu viruses rise.
Others, like infectious disease specialist Jeremy Luban of Harvard Medical School, said human behavior likely still plays a role in our changing viral streams. The closures, while brief in many places, might have been enough to change seasonal patterns. And many American schools were closed much longer than businesses. If we dodge a season or two of flu, RSV, and adenovirus, populations might have less immunity to them later on.
He said that could help explain the mysterious clusters of hepatitis that have sprung up in 35 countries around the world since last spring, in some cases leading to liver transplants. The latest thinking, which emerged at a major meeting earlier this month, points to a co-infection of two interacting viruses.
One was adenovirus and the other an adeno-associated virus. This virus, called AAV2, needs the adenovirus to replicate. In several recent studies, almost all children with hepatitis tested positive for AAV2, but none of the children in a control group were. Similar infections may have occurred before the Covid era, but only became apparent when adenovirus had an unusual rise after Covid mitigation measures were lifted.
Biologist Andrew Read, who studies pathogen evolution at Penn State University, said he wouldn’t rule out discontinued mitigations as a factor in the virus surges we’re seeing now. He says it’s possible these other viruses are inherently less transmissible than SARS-CoV-2, so their spread was suppressed for a couple of years by the same measures that failed to contain Covid. But it is not known whether one or two years of decreased transmission would have a significant impact on population immunity. “We really don’t have good data on that,” he said.
He said he is particularly concerned about the adenovirus cases that have reportedly sent several University of Michigan hockey players to the hospital and at least one to the ICU. “The idea that there is a problem with young people because of adenoviruses is really amazing,” he said. It could be a fluke: the tip of a large iceberg of mild cases of adenovirus. But it could also be something more worrisome. “We are in new territory,” he said.
That leaves the question of whether all these cases of flu, RSV and adenovirus will leave populations awash with interferons that could slow down the next wave of covid. Something strange is already happening: a new wave of omicron called BQ.1.1 has started, but as physician Eric Topol writes in his newsletter, this is the first new variant to become dominant without causing a new wave of cases or hospitalizations.
I am cautiously optimistic that we will not see a massive quadrupleemia this winter, if only because other viruses could displace Covid. But as we learned just a year ago, when omicron hits, Covid can always hit us with something from left field.
This column does not necessarily reflect the opinion of the editorial board or of Bloomberg LP and its owners.
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