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“This is not typical of any time of year, and certainly not typical of May and June,” said Thomas Murray, an infection control expert and associate professor of pediatrics at Yale. Some hospitalized children have been co-infected with two viruses and some with three viruses, he said.
More than Two years into the coronavirus pandemic, familiar viruses are behaving in unusual ways. The respiratory syncytial virus, known as RSV, typically confines its suffocating attacks to the winter months.
Rhinovirus, cause of the common cold, rarely sends people to the hospital.
And the flu, which appeared to be making a comeback in December after not showing up the year before, disappeared in January as the Omicron variant of the coronavirus took hold. Now the flu is back but without a common lineage called the Yamagata, which has not been spotted since early 2020. It could be extinct or lying in wait to attack our unsuspecting immune systems, researchers said.
The upheaval can be felt in hospitals and laboratories. Doctors are rethinking routines, including keeping preventive vaccinations well into the spring and even summer. Researchers have a rare opportunity to determine whether behavioral changes such as house bans, masking, and social distancing are responsible for the viral shifts and what evolutionary advantage SARS-CoV-2 might wield over its microscopic rivals.
“It’s a huge natural experiment,” said Michael Mina, epidemiologist and chief science officer at digital health platform eMed. Mina said the shift in seasonality is largely explained by our not having been exposed to common viruses recently, leaving us vulnerable to their return.
In hospitals across the country, doctors are adjusting protocols that for decades reflected a predictable cycle of diseases that came and went as schools closed or the weather changed.
“You would see a child with a feverish illness and think, ‘What time of year is it?’ said Peter Hotez, molecular virologist and dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston.
For years, Theresa Barton, chief of the division of pediatric infectious diseases at University San Antonio Health, has routinely advocated the flu vaccine each fall, relaxing her endorsement in March and April as the flu fizzled out. The new shift in seasonality, with flu cases rising last summer and then again this spring, caused them to rethink.
“You’re like, ‘Oh man!’ in clinics. ‘Let’s get your flu shot,'” Barton said.
She and other infectious disease specialists also check their response to RSV, a common virus that hospitalizes about 60,000 children under the age of 5 each year, according to the Centers for Disease Control and Prevention. It can cause fatal lung infections in preterm and other high-risk infants. The typical treatment for them is monthly shots of a monoclonal antibody, palivizumab, from around November to February. But last summer the RSV suddenly went up and this year it’s causing trouble in May and June. Infectious disease experts are carefully tracking cases so they are ready to reactivate the costly protocol.
“We’re monitoring the number of cases so if it crosses a number, we’re ready,” Murray said. Yale Hospital, which normally holds sessions from fall to spring to prepare for upturns, is preparing pandemic-weary staff for off-season surges.
According to Richard Martinello, a respiratory virus specialist at Yale School of Medicine, even the common cold seems to be a bit more virulent and persistent.
“When people have a cold, they seem to get a little worse,” he said, stressing that the evidence so far has been largely anecdotal.
The changes—and how and when they might return to normal—reflect changes in our own behavior during the pandemic, as well as the interplay between SARS CoV-2 and other viruses, known as viral interference.
We evolved along with pathogens, and our regular exposure to them usually allows our immune system to ramp up the response without making us very sick.
The system has “enough memory to make it a good, hearty booster rather than a bad infection,” Mina said.
The moment you stop seeing a virus at this regular rhythm, as it has been during the pandemic, that natural balance is disrupted, Mina said. The extraordinary measures we took to limit exposure to the coronavirus — necessary steps to contain a deadly new enemy — also limited our exposure to other viruses. If you’re exposed to a virus again after too long, you may not be able to protect yourself as well, leading to an off-season population surge and surprisingly virulent infections for individuals.
That, Mina and others say, happened when people took off their masks and began congregating indoors. Viruses began to circulate out of season because the population’s immunity was low, even when other conditions were not optimal for them.
“All of these decisions have consequences,” Murray said. “You’re doing the best you can with the information you have.”
The same immune memory process is already well documented by other phenomena, Mina said, such as 35- and 40-year-olds who get shingles, a reactivation of the chickenpox virus that typically affects older adults or people with compromised immune systems.
Before the advent of chickenpox vaccines, people were typically infected as children and then experienced a series of natural strengthening events throughout their lives that rebooted their immunity as they interacted with infected friends, and then with their own children and their children’s friends contact came.
Now that these children are protected, they do not give their parents these natural impulses, once again making these adults vulnerable to the virus in the form of shingles.
This phenomenon will be short-lived as younger people who are protected by the chickenpox vaccine age and are not at risk of getting shingles.
While vaccines are disrupting the viral landscape by limiting the spread of infection, an entirely new virus — SARS Cov-2 — is doing so during the pandemic by interacting with its more common rivals.
It’s not yet clear whether January’s drop in flu cases, for example, was entirely due to people pulling back together as Omicron spread, or whether the coronavirus pushed aside its more common rival through some other mechanism.
“It’s a wonderful question whether Omicron has supplanted it,” said Xiaoyan Song, senior infection control officer at the district’s Children’s National Hospital. Even more mysterious is the role Covid played in taking Yamagata out of the game. When the flu returned this spring, that lineage was nowhere to be found.
Ellen Foxman, an immunobiologist at Yale School of Medicine, has spent years studying how viruses interact and what genetic and environmental factors mean that the same virus can cause one person to catch a cold and another to be very ill.
It’s a high-tech company that uses cells from the nose and lungs to grow human respiratory tissue in the lab before infecting it with viruses and environmental pollutants like cigarette smoke.
Examination of the lining of the nasal passages has provided insight into what is known as innate immunity. As soon as these cells recognize a virus, they turn on the antiviral defenses and block other viruses. This process may explain why the much-anticipated twin demise of coronavirus and other viruses, likely stifled by remote working and masking during the winter of 2020-2021, has still not emerged last winter despite sporadic co-infections.
The cohort of babies born in the last two years will provide a lot of information. Normally, a child under the age of 5 has a virus in their nose for an average of 26 out of 50 weeks a year. Severe RSV and Rhinovirus Infections in these early years are associated with the development of asthma later in life.
“These children had no infection at a crucial time in lung development,” Foxman said, making it key to understanding the relationship between viral infection and asthma.
Still, it’s not clear what the future holds as Covid nests among us.
“It will take time and even years to see what the new balance will look like,” Martinello said.
Mina posits that the coronavirus, like other respiratory viruses, will fall into a pattern of seasonal circulation as population immunity increases, reducing what it calls the “infectious power.”
“If you have a lot of people who don’t have immunity, the impact of the season is less. It’s like a free hand,” Mina said. The virus “can overcome seasonal barriers”.
All of these shifts are influenced by other environmental factors, Barton says, as climate change alters seasonal weather patterns.
Despite these ongoing uncertainties, for many researchers the upheaval caused by the pandemic has reinforced known infection prevention strategies.
Scott Hensley, a microbiologist at the University of Pennsylvania’s Perelman School of Medicine, isn’t convinced the Yamagata flu is gone forever. It could still be circulating undetected at very low levels, he said, ready to get back on the scene. However, there is a proven method to protect yourself – through vaccination.
“Even in years when vaccines don’t match, there is some level of protection,” Hensley said, “to prevent hospitalizations and deaths.”
For Foxman, the laboratory scientist, the silver lining of the pandemic was how it will advance science.
Even as she continues to invest in high-tech experiments in her lab, Foxman says the biggest lesson the pandemic has taught her about stopping the spread of viral infections comes from simple behavior changes like masking, which she believes are strategic should continue circumstances.
“We need to carry on some of the lessons we’ve learned,” Foxman said.
