Respiratory viruses, thrown out of whack by Covid, appear to be falling back into seasonal order

In the depths of the Covid-19 pandemic, something strange happened: For a year or two, illnesses that used to emerge like clockwork when fall and winter arrived — flu, RSV, and the myriad viruses that cause colds — did not sicken us.

The cause now appears clear: The measures we took to avoid the new disease, including isolating and social distancing, muscled most other respiratory pathogens out of the cold-and-flu-season picture.

When we started to tire of altering our lives to avoid SARS-CoV-2, which causes Covid, those other viruses returned — but at odd times and behaving in odd ways. Rhinoviruses — aka common cold viruses — made children in Hong Kong so sick they ended up in hospital. In late August and September of 2022 in parts of Europe and North America, RSV-infected children overwhelmed pediatric hospitals, months earlier than respiratory syncytial virus seasons occurred in pre-Covid times. Shortly thereafter, flu transmission kicked into gear, peaking just after Thanksgiving in this country — unusually early for influenza.

Now, as we head into the fourth Northern Hemisphere winter of the Age of Covid, respiratory viruses appear to be falling back into seasonal order, experts tell STAT.

Late summer RSV was not a thing in 2023, as it was the past two years. And flu activity is only now starting to amplify, just in time for the intergenerational mixing — and germ swapping — events that we know of as Thanksgiving and Christmas.

The early signals from influenza suggest the virus is settling back into the seasonal pattern it followed — to the degree the always mercurial bug follows any pattern — before the pandemic, said Alicia Budd, team lead for domestic flu surveillance at the Centers for Disease Control and Prevention. “All I can say is at this point we are at a pretty typical point in flu activity,” she told STAT.

Overall, the signs to date appear to portend a winter more like what we knew before the arrival of Covid, said Megan Culler Freeman, an assistant professor of pediatrics specializing in infectious diseases at the University of Pittsburgh.

“Last year as early as August, children’s hospitals across the country were full to the gills … because there were so many children with respiratory distress,” Freeman said. “And I would say that this season is starting to feel a lot more normal. Only now, as we’re getting into November — even towards mid- to late- November — we’re starting to see more of our winter volume starting to begin.”

Petter Brodin, a professor of pediatric immunology at Imperial College London, agreed that respiratory diseases seem to be heading back towards their regular seasonal slots, though he noted that “it’s different for different viruses, so it’s a little difficult to speak in general terms.”

The return to normal hasn’t happened in a synchronized fashion around the globe, though. Ben Cowling, chair of epidemiology at Hong Kong University’s School of Public Health, said respiratory diseases seasonality in China and Hong Kong — both of which used aggressive Covid containment measures for longer than many other places — is still not as close to pre-pandemic normal as it appears to be in North America and Europe.

Flu circulation, for instance, only returned to Hong Kong in the spring of 2023, shortly after mask mandates were relaxed, Cowling and colleagues reported recently in an ahead-of-print paper published in the journal Emerging Infectious Diseases. The spring activity was followed by a large swell of influenza A transmission — H3N2 viruses specifically — in October. Flu can circulate year round in Hong Kong, Cowling said, but he noted October is a pretty atypical time for a wave of flu there.

“I don’t think we’re back to normal seasonality yet here, and not in China. But I agree with [the] observation that in some places it does seem to be going back to how it had been before. The question, though, is about how Covid will go in that mix?” he said.

The scientific consensus is still out about whether Covid will be a seasonal virus, transmitting primarily during cold-and-flu season. Many experts think it is heading that way, but hasn’t yet settled into that pattern.

On the question of what caused the temporary disappearance of Covid’s viral rivals, there appears to be broad agreement that the control measures used to slow spread of SARS-2 impeded the ability of other viruses to circulate. The resulting hiatus in exposures to these bugs eroded the amount of immunity humans had to them at a population level, creating a larger-than-typical number of vulnerable people when we let down our Covid guards.

Brodin likened the situation to the conditions that precede wildfires. “You have the possibility of triggering a forest fire at any time of the year, but it’s only when you have enough … flammable dry wood, for example, or whatever that it really flames up,” he said. “And so I think the reason why it happened at different times in different countries is because at that time there were sufficient numbers of individuals that were susceptible, that did not have immunity and then you started seeing this.”

A primary driver of the phenomenon was the fact that with school closures and social distancing, young children weren’t contracting the cascades of infections they generally experience in their first years of life. Those infections build up their immunity to viral threats; missing them made this group both especially vulnerable and unusually large when the viruses returned. “So as the years rolled on, and there wasn’t very much RSV, it just left a huge susceptible population of infants — 1-year-olds, 2-year-olds, 3-year-olds, 4-year-olds last year that had never seen RSV before,” Freeman said.

Though children get infected with RSV repeatedly in early childhood, their first bout typically is the most severe, and the most likely to send them to hospital. In 2022, when the RSV onslaught was at its worst, the peak of hospitalizations was four times higher than it had been in previous RSV seasons, Freeman said.

That massive surge of RSV cases will have reset susceptibility levels in the pediatric population. “I would expect that all those kids that were exposed last year are going to have a little bit of protection this year that shouldn’t make it as severe of a season,” she said. “The birth cohort that is naive to RSV [this year] is more typical for the levels that we usually see in a given winter.”

Brodin described this pattern — the unusually large group of vulnerable children — as a “numbers game.”

“How many susceptible children do you have at any particular time in a given place, and is that enough to get the transmission going?” he said.

While children are major amplifiers of many respiratory diseases, the break from exposure to influenza and other viruses will have created more susceptibility among adults as well, said Florian Krammer, an influenza virologist at Mount Sinai School of Medicine in Manhattan. That, in turn, could have led to the early start of the 2022-23 flu season.

“I think, in general, if … the population is not bombarded with viruses, the immunity might go down a little bit, and that might give different opportunities to the virus to maybe circulate under circumstances where it usually doesn’t transmit well,” Krammer said in an interview. “Maybe it doesn’t need the cold temperature, and it can start when it’s a little bit warmer. There’s a lot of factors that could influence that.”

Human behavior and weather — especially in temperate climates — dictate the seasonality of viruses, said Ellen Foxman, an associate professor of laboratory medicine and immunobiology at Yale University School of Medicine. The human activities that were so heavily altered in the early part of the pandemic — closed borders, sharply reduced international travel, far less social mixing — had a huge impact on the spread of other viruses. But those days have come to an end and the return to pre-Covid behavior is pushing us back towards pre-Covid disease patterns, she suggested.

“We’re going to work, going to school. Kids are going to daycare. All those behavioral things that influence viral transmission are getting back to normal,” Foxman said. “In that regard I feel like those things are normalizing, and the more time that goes by that those things are normal, that will probably influence our viruses to behave as they did before.”

Foxman uses a different analogy to describe what has happened with seasonal respiratory diseases in the post-Covid era.

“It’s like when a pendulum swings back and forth, and then its periodicity gets messed up, you know? It takes a while for it to get back to what it was before. And I think we had a big pendulum swing in one direction. Then we had a big pendulum swing in another direction last year,” she said. “I don’t know if we’re really back to normal yet or not. I don’t know if that pendulum is still swinging a little bit out of its normal periodicity, to extend the analogy. … The next few months will really tell.”

Scott Hensley, a professor of microbiology and an influenza expert at the University of Pennsylvania, also believes this winter will tell the tale regarding whether the seasonality of non-Covid respiratory viruses has really returned.

“Could I let you know in, like, March?” he quipped when asked his thoughts.

“Right now in Philadelphia, flu activity is super low — as it should be,” Hensley said. “I think last year we did have this highly unexposed population — or not recently exposed population — where there was a little bit of fire and everything just ignited. But I do think that things seem to be kind of settling back into a normal rhythm, so we’ll see if cases start increasing in the next month or so.”