Something is altering the normal seasonal currents of cold and flu viruses. They slowed to a trickle during the early part of the COVID-19 pandemic only to blast through human populations this year. Some public health experts have called it a “tripledemic,” but it might even be described as a quadrupledemic.
In the Northern Hemisphere, flu began surging in October, months before its normal season. This year has also seen a steep, early rise in two other viruses, RSV (respiratory syncytial virus) and adenovirus. These normally cause colds, but RSV can be dangerous to young children and has recently led to overcrowding of children’s hospitals. Adenovirus is usually mild too, but this month there were reports of the virus putting college athletes in the ICU, and it’s been implicated in clusters of dangerous hepatitis cases in children.
Why now? The easy answer is that wearing masks for more than two years drove down the incidence of these viruses, and people subsequently lost 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 a way that’s not understood, said Michael Osterholm, director of the Center for Infectious Disease Research and Policy and host of a podcast on COVID-19.
“When multiple respiratory viruses are circulating in a given season, one of them will dominate for reasons we don't understand,” he said on the podcast. “There's something going on there that can't be just attributed to personal protection (or) distancing.”
A few other researchers made a similar observation last week in Science. “Flu and other respiratory viruses and SARS-CoV-2 just don’t get along very well together,” virologist Richard Webby told the magazine. Or as epidemiologist Ben Cowling of the University of Hong Kong put it, “One virus tends to bully the others.”
That means that viral interference might be more of a factor than immunity debt.
Osterholm points out that the same suppression of other viruses happened in 2009 when the H1N1 flu broke out. “For the first time in years, we didn't see other influenza strains like H3N2 and or any of the RSV activity. It just disappeared,” he said. “It can't be because of mitigation, because we didn't do mitigation.”
He said he also doubts mitigation was all that effective against RSV and flu because it wasn’t terribly effective against COVID-19 — 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’s much less evidence behind the kinds of loose-fitting cloth masks common in school settings (though closing schools likely did perturb the course of other seasonal viruses).
Viral interference might offer a more complete explanation. Our innate immune system includes disease-fighting substances called interferons, which may protect people infected with one virus from getting another. That may be why, as a large study from the University of Glasgow published in 2019 showed, cold viruses sink as flu viruses rise.
Others, such as infectious disease specialist Jeremy Luban of Harvard Medical School, said human behavior is still likely playing a role in our shifting viral currents. Lockdowns, though brief in many places, might have been enough to shift seasonal patterns. And many US schools were closed much longer than businesses. If we dodged one or two seaons of flu, RSV and adenovirus, populations might have less immunity to them later.
He said that might help explain the mysterious clusters of hepatitis that cropped up in 35 countries around the world starting last spring — in some cases, leading to liver transplants. The latest thinking, which came up at a major meeting earlier this month, points to a co-infection of two interacting viruses.
One was the adenovirus and the other an adeno-associated virus. This virus, called AAV2, needs the adenovirus to replicate. In several recent studies, nearly all the children with hepatitis were positive for AAV2, but none of the children in a control group were. Similar infections might have happened before the COVID-19 era, but only became noticeable when adenovirus had an unusual surge after COVID-19 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 viral surges we’re seeing now. He says it is possible that 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-19. But it’s not known whether a year or two of decreased transmission would have a significant impact on the population’s immunity. “We really don’t have good data on that,” he said.
He said he’s particularly concerned about the adenovirus cases which reportedly sent several University of Michigan hockey players to the hospital and at least one to the ICU. “The idea that there’s a problem with young people from adenoviruses — that’s really striking,” he said. It might be a fluke – the tip of a big iceberg of mild adenovirus cases. But it also might be something more worrisome. “We’re in new territory,” he said.
That leaves the question of whether all these flu, RSV an adenovirus cases will leave populations flush with interferons that might tamp down the next wave of COVID-19. There is something weird already going on — a new omicron wave called BQ.1.1 has begun, but as physician Eric Topol writes in his newsletter, this is the first new variant that’s become dominant without causing a new wave of cases or hospitalizations.
I’m cautiously optimistic that we won’t see a massive quadrupledemic this winter, if only because COVID-19 could be crowded out by other viruses. But as we learned just one year ago, when omicron hit, COVID-19 can always hit us with something from left field.
