A curious thing happened during the Covid-19 pandemic: With masks, social distancing, and Purell galore, we kept most other germs at bay.
Flu vanished. Cases of respiratory syncytial virus, or RSV, which in a normal winter puts nearly 60,000 children under age 5 in the hospital, were nonexistent. Most of us appeared to sidestep the soup of bugs that cause colds.
But as masks come off, schools reopen, and some travel resumes, we should expect a resurgence of these viruses — perhaps a big one. Some experts fear we’re in for a nasty cold-and-flu season or two, pointing to a combination of factors that could make for a rough re-entry to the mixed microbes world.
“When they come back there’s going to be vulnerability and probably greater levels of infections,” Ben Cowling, an infectious diseases researcher at Hong Kong University, said of the various bugs. “Everyone’s going to be complaining about colds probably next winter.”
In fact, the resurgence has already started. Case counts of RSV — which causes colds for most people but can be a serious threat to little children and older adults — have been ticking up in a number of places in the country in recent weeks, including Brooklyn. In Utah, doctors in the Intermountain Healthcare network normally see about 300 or more RSV-infected children a week during the peak of a regular season; this winter a handful of cases was reported. But nearly 10 times that many have been reported since mid-May.
Trevor Bedford, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle, has been monitoring which viruses are circulating through Nextstrain, a program that tracks the genetic evolution of pathogens and the Seattle Flu Study. After SARS-CoV-2 took root in the U.S., for a full year the only things being reported were Covid cases and rhinovirus infections. Not anymore.
“Just in the last month or so we’ve started to pick up small amounts of seasonal coronavirus, RSV, metapneumovirus, etc. It’s the first time since April 2020 where we’re starting to see other things circulating,” Bedford said.
The viral reprieve: A boon and a bane
Not having to fend off colds and flu during the worst of Covid has obviously been a blessing, for us as individuals and for the health care system. But that period when we’ve been sheltered from viral challenges will likely come with a cost when we de-mask, return to office work, and start to be in closer proximity to others again.
In normal times, we’re often in contact with viral respiratory pathogens. Sometimes we get sick, but sometimes those exposures just boost our immune defenses against that particular threat. “Even if you just get exposed and there’s not much replication and you don’t get sick, there’s a restimulation of T-cells,” said Florian Krammer, a vaccinologist at Mount Sinai School of Medicine in Manhattan.
A year and a half without these boosts to our adaptive immunity — the part of the immune system that relies on the memory of previous exposures to activate defenses — could mean many of us are that much more susceptible to these bugs, Krammer said. “There’s just lower levels of adaptive immunity in the population for them.”
Time to talk about the kids
This period of viral inactivity will likely have an impact on adults. But it will definitely have an impact on children.
As any parent, daycare worker, or elementary school teacher will attest, children are germ amplifiers. Within a few weeks of the start of the school year, they start getting sick — infecting each other and the adults in their orbits. A lot of that normal bug-swapping activity didn’t happen when kids were being schooled remotely and didn’t have as much contact with people outside their households.
The experience of Hong Kong schools late last year tells us what we can probably expect when in-person teaching resumes here. Cowling and colleagues reported in February on an explosion of rhinovirus outbreaks throughout the city-state’s schools, when they were re-opened last October after months of at-home learning. Some children got so sick they ended up in hospital. Rhinoviruses are the most common cause of the common cold.
Ellen Foxman, an immunologist who studies rhinoviruses as part of her research on the innate immune system at Yale University, said she expects similar activity here. (The innate immune system is the part that isn’t threat-specific; it’s the general, non-specific response that kicks into gear when the body recognizes there’s an invader.)
“I can imagine that when things first start up again in the fall and all the kids go back to college and other kids go back to elementary school and preschool and daycare that you will have a lot of respiratory virus transmission,” Foxman said.
Really young children will have been sheltered during a period in their lives when they would typically have a lot of encounters with respiratory viruses. “We now have some kids who’ve never been exposed to things who are going to go to daycare for the first time,” she noted.
Andrew Pavia, chief of the division of pediatric infectious diseases at the University of Utah, is worried about RSV. “There will be two years’ worth of kids who are naïve to RSV in the U.S., instead of one birth cohort. That could be fertile ground for a big RSV year,” he warned earlier this spring on Twitter.
In an email, he said that U.S. children’s hospitals are on edge having seen western Australia reporting large out-of-season RSV outbreaks over that country’s summer.
Likewise little kids may be hit hard by flu, when it returns. This past winter, the Centers for Disease Control and Prevention was informed of only a single child who died from flu in the United States. Pediatric flu deaths must be reported to the CDC; most years there are somewhere between 150 and 200 such deaths.
A swell of rhinovirus infections might actually help to quell Covid and flu infections, at least for a while, research from Foxman’s laboratory suggests. The effect was seen in the timing of the fall wave of the H1N1 flu pandemic in Europe, she and colleagues reported in the journal Lancet Microbe. Working in organoids of airway epithelial cell tissues, they saw the same short-term inhibition of SARS-CoV-2 infections following rhinovirus infections. That work is reported in a preprint, meaning it has not yet gone through peer review.
“I’m of the camp that once viruses are circulating around, those innate immune responses provide a general level of protection against things getting too crazy and too out of hand with respiratory viruses,” Foxman said.
Several big question marks hang over influenza
There was no flu season this past winter. Influenza scientists are worried that is setting us up for a big flu season soon, with more susceptibility.
Cécile Viboud, an epidemiologist at the National Institutes of Health’s Fogerty International Center, isn’t sure lots of flu will translate into lots of severe flu. “There is some residual level of immunity and also we think immunity goes beyond one year or two years or 15 months,” she said. And, she noted, there’s flu vaccine.
“I think it will depend on the fraction of people who get vaccinated next fall,” Viboud said. “I’m sure there will be a lot of messaging to try to encourage that because everyone’s worried about that.”
During the pandemic an unusual phenomenon has been observed with flu viruses that is a source of hope for some and concern for others. There’s a lot less genetic diversity among the viruses. That, the glass-half-full types point out will make it much easier to select the strains for flu shots.
But others, including Scott Hensley, an influenza expert at the University of Pennsylvania’s Institute of Immunology, see risk.
“When we see this real narrowing of the genetic diversity of flu, I think that’s indicative of a narrowing to only those strains that are super highly transmissible or those that at least have a fitness advantage, whether it’s an increase in transmissibility or an increase in immune escape,” said Hensley. “Whatever it is, most of the viral lineages have been whittled out and what we’re left with I’m afraid might be the most fit strain.”
Krammer doesn’t share that fear, saying he thinks the viruses that have survived may have been in the right place at the right time to infect people. “I think it might not be necessarily an effect of fitness, it might be more an effect of basically randomness.”
Another question hanging over flu is how much of it we’ll see in North America next winter. The spread of flu relies heavily on international travel, which remains well below pre-pandemic levels at this point.
“It’s hard to judge because I don’t know what will happen to international travel,” Krammer, who predicts a bad flu season soon, said when asked when to expect it.
“It might be the next season, it might be the season afterwards, and it could be that I’m completely wrong,” he said. “But I think either this or next winter season might be a really bad flu season.”
Predicting viral behavior is tricky business
Many physicians and researchers who work on infectious diseases share Krammer’s sense of dread that the revenge of the respiratory pathogens will be playing out across the Northern Hemisphere this coming fall and winter. But the reality is these are hunches. Informed hunches, to be sure. But hunches still.
Remember, last fall there were dire warnings about the looming “twindemic” — with public health leaders predicting that health systems collapsing under the weight of Covid cases would be hit by a surge of flu infections as well.
Never happened. Flu transmission occurred at minimal levels in most of the world in the Northern Hemisphere winter. The CDC reported last week that the cumulative rate of people hospitalized for flu this past winter was fewer than 1 person per 100,000 people — one-tenth the rate in 2011-2012, which was a historically low-severity flu season.
Best to keep that in mind when looking to what winter 2021-2022 will hold, some experts advise.
“Well, I don’t have a crystal ball and … I don’t think anybody knows for sure what’s going to happen when things open up again,” Yale’s Foxman said. “I think it’s going to be fascinating to see what happens this coming year. It’s really a complex interplay of immunology and human behavior.”
She and others who spoke with STAT stressed that latter factor, saying effectively this: We are not without ammunition in this upcoming battle. We may be tired as hell of Covid-suppression measures, but we’ve learned they actually keep other respiratory pathogens in check.
“I can’t imagine that won’t have some impact on people’s behavior,” Foxman said. “I don’t think we can cancel international travel or work from home forever. But I bet you this will change the culture around people going to work sick or sending their child to school sick, which was a very common occurrence pre-Covid.”
The flu vaccine contains a coronavirus adjuvant, meaning it could trigger ADE (antibody dependent enhancement) in those that have received an mRNA (Pfizer/Moderna) covid vaccine. Watch for patterns.
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