Brace Yourself for a Triple Wave of Seasonal Viruses

Every year it’s the same. As soon as it starts to get cold, people gather indoors. Windows are pulled shut. Commuters forgo walking or cycling, opting for packed buses and subways. Our whole world retreats to where it’s warm, our breath condensing on the windows of homes, offices, schools, and transport, showing just how well we’ve sealed ourselves off from the outside. We create, in short, the perfect breeding ground for viruses.

When the respiratory virus season begins, it’s usually quite predictable. Patients start being admitted to hospitals with influenza or respiratory syncytial virus (RSV) around October in the northern hemisphere. Thousands of people get ill, and many die, but the odd extreme year aside, health systems across Europe and North America aren’t typically at risk of being overwhelmed.

But the pandemic has derailed this predictability. It has added another virus to the seasonal mix, and flu and RSV are returning this year with a vengeance. A “twin” or even “tripledemic” could be on the way, with all three viruses hitting at once, illnesses soaring, and health systems creaking under the pressure. Already there are signs this is happening.

Many hospitals in the US are at capacity, caring for large numbers of children infected with RSV and other viruses, many more than would be expected at this time of year. The US Centers for Disease Control and Prevention (CDC) doesn’t track RSV cases, hospitalizations, and deaths as it does for flu, but hospitals across the country have been reporting peak levels typically observed in December and January. Nearly one in five PCR tests for RSV came back positive in the week ending October 29, with this rate having doubled over the course of a month. Generally speaking, the higher the proportion of tests that come back positive, the more common a virus is in the wider community. In the three years before the pandemic, an average of just 3 percent of tests came back positive in October.

This is a hangover from the pandemic. Over the past two years, RSV and flu were kept down thanks to the protective measures people took against the coronavirus: mask wearing, hand washing, and isolating. Between the beginning of the pandemic and March 2021, the weekly positivity rate for RSV tests remained below 1 percent, according to the CDC—down where it was in pre-pandemic times.

In July of this year, health specialists warned in The Lancet that the benefits of these pandemic precautions could end up having a negative effect this winter season. Reducing exposure to common endemic viruses such as RSV and flu, experts argued, risked creating an “immunity gap” in people either born during the pandemic or who hadn’t previously built up sufficient immunity against these viruses.

That prediction now appears to be coming true, as children are catching these viruses for the first time, without having built up any prior immunity, and falling badly ill. “We’re seeing kids at older ages getting RSV that would have previously got it at a younger age,” says Rachel Baker, an assistant professor of epidemiology at Brown University in Rhode Island, who was a coauthor of the Lancet comment piece. “That’s putting some pressure on hospitals.”

RSV typically causes mild cold-like symptoms, but infections can be dangerous for infants. Their tiny lungs and muscles cannot muster the strength to cough up or sneeze out the mucus in their airways. Deaths are rare, but the virus can kill. Adults with weaker immune systems are vulnerable too, such as those with underlying health conditions or who are very old. Unlike for Covid-19 and flu, there are currently no approved RSV vaccines (Pfizer has one in trials, given to pregnant people to protect infants, that may become available next year).

Flu hospitalizations have also been higher than usual for this time of year—13,000 adults and children have been hospitalized in the US so far, and 730 people have died. “We’re seeing the highest influenza hospitalization rates going back a decade,” José Romero, director of the CDC’s National Center for Immunization and Respiratory Diseases, said on November 4. And a similar picture is emerging across Europe. The United Kingdom’s Health Security Agency said in late October that hospital admissions for respiratory diseases are rising, and they’re climbing fastest in children under 5.

The fact that the southern hemisphere is coming off a pretty bad winter season—Australia experienced its worst flu season in five years—is another signal that the northern hemisphere is in for a rough one. Flu viruses that circulate during the southern hemisphere winter often end up infecting people in the north six months later, so more illness in Australia suggests this winter’s flu in the US and Europe will be particularly virulent. “For many healthy adults this will predominantly be an inconvenience, but for vulnerable groups this could be a concern,” says Neil Mabbott, professor of immunopathology at the University of Edinburgh in the UK.

This winter will be the first time that these three respiratory viruses can circulate completely freely, meaning there is a real prospect of things getting worse. But SARS-CoV-2, because of its ability to mutate, is a wildcard when trying to guess exactly what will happen. “It’s like a dream and a nightmare for someone doing prediction,” says Mary Krauland, a research assistant professor who models SARS-CoV-2 and influenza outbreaks at the University of Pittsburgh.

Because there are no plans to reintroduce control measures, Krauland says it is quite possible that SARS-CoV-2 infections will surge again this winter, ratcheting up pressure on health services. It is unclear whether that surge would collide with the influenza and RSV peaks. “You can imagine many scenarios, but it’s very difficult to pin down which one is the most likely,” she says. At the moment, most Covid cases are caused by lineages of the Omicron variant that seem to cause milder disease than earlier forms of the virus but which are able to dodge immunity from vaccines and previous infections. These variants and subvariants also compete with each other for human hosts. Should a new, more infectious variant emerge and outcompete the others, Krauland says, infections could rise sharply again. Hospitals could then feel the effects, because as infections accumulate, the number of hospitalizations and deaths also increase.

For the health system, two or three simultaneous epidemics is a worrying scenario, but so too is the prospect of contracting more than one virus at the same time. Scientists are not sure how the viruses interact, but there is evidence that simultaneously catching SARS-CoV-2 and influenza increases the risk of severe illness and death. In a study of nearly 7,000 hospitalized patients with Covid-19, researchers in the UK found that 227 patients had also tested positive for the flu, and they were more likely to require ventilation.

But how the influenza and RSV viruses interact and influence the course of disease is not clear: There have been few studies investigating this, with conflicting results, says Pablo Murcia, professor of integrative virology at the University of Glasgow. This is due to various confounding factors that muddy the water in coinfections, such as a patient’s preexisting conditions or their immunological status, the strains of viruses involved, or the time that’s elapsed between the first and second viral infection.

Catching both viruses at the same time is a troubling possibility. In a lab experiment, Murcia and his team deliberately infected human lung cells with both viruses and found that they fused together to form a palm-tree-shaped hybrid virus—with RSV forming the trunk and influenza the leaves—which could infect new cells even in the presence of flu antibodies, in essence using its new form to bypass existing flu immunity. Their findings were published in the journal Nature Microbiology in October. But it’s not known whether hybrid viruses form in people, and if they do, whether they cause disease, says Murcia.

Krauland expects that few people will contract multiple viruses at once, provided they stay at home as soon as they notice any symptoms of infection, even if mild. “The three are kind of competing for hosts at this point,” she says, and if they are, this could lead to all three viral waves being flattened. But whether this will happen—and if so, if it will keep hospitals from buckling under the pressure—we probably won’t know until spring.

Brace Yourself for a Triple Wave of Seasonal Viruses

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