For more than two years, shuttered schools and offices, social distancing and masks granted Americans a reprieve from flu and most other respiratory infections. This winter is likely to be different.

With few to no restrictions in place and travel and socializing back in full swing, an expected winter rise in COVID-19 cases appears poised to collide with a resurgent influenza season, causing a so-called twindemic” — or even a tripledemic, with a third virus, respiratory syncytial virus, or RSV, in the mix.

Cases of flu have begun to tick up earlier than usual and are expected to soar over the coming weeks. Children infected with RSV (which has symptoms similar to those of flu and COVID-19), rhinoviruses and enteroviruses are already straining pediatric hospitals in several states.

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“We’re seeing everything come back with a vengeance,” said Dr. Alpana Waghmare, an infectious diseases expert at Fred Hutchinson Cancer Center and a physician at Seattle Children’s Hospital.

Most cases of COVID-19, flu and RSV are likely to be mild, but together they may sicken millions of Americans and swamp hospitals, public health experts warned.

“You’ve got this waning COVID immunity, coinciding with the impact of the flu coming along here, and RSV,” said Andrew Read, an evolutionary microbiologist at Penn State University. “We’re in uncharted territory here.”

The vaccines for COVID-19 and flu, while they may not prevent infection, still offer the best protection against severe illness and death, experts said. They urged everyone, and especially those at high risk, to get their shots as soon as possible.

Older adults, immunocompromised people and pregnant women are most at risk, and young children are highly susceptible to influenza and RSV. Many infected children are becoming severely ill because they have little immunity, either because it has waned or because they were not exposed to these viruses before the pandemic.

RSV causes about 14,000 deaths among adults 65 and older and up to 300 deaths among children younger than 5 each year. No vaccine is available, but at least two candidates are in late-stage clinical trials and appear to be highly effective in older adults. Pfizer is also developing an antiviral drug.

“As of today, we are seeing equal numbers of COVID, flu and RSV, and that’s really concerning because we are very early for flu and RSV activity,” said Dr. Diego Hijano, a pediatric infectious disease specialist at St. Jude Children’s Research Hospital.

“It’s going to be a rough winter,” he said.

Another COVID-19 Wave?

Coronavirus cases are low but are beginning to rise in some parts of the country. Several European countries, including France, Germany and Britain, are experiencing an uptick in hospitalizations and deaths, prompting experts to worry that the U.S. will follow suit, as it has with previous waves.

Some of the coronavirus variants that are picking up momentum are adept at dodging immunity and drugs such as Evusheld and Bebtelovimab, which are especially important for protecting immunocompromised people.

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