Why 100 million Americans could be infected during COVID surge this fall

Experts say cases will rise as immunity wanes and people move indoors.

The Biden administration's stark warning last week that as many as 100 million Americans could be infected during a COVID-19 wave in the fall and winter came as a shock to many in the country.

After all, 70.5% of the eligible U.S. population aged 5 and older are fully vaccinated and 47.8% of those aged 12 and older are boosted, according to the Centers for Disease Control and Prevention.

What's more, a recent CDC analysis estimated at least three out of every five Americans have antibodies that indicate being previously infected with COVID-19, meaning most people in the U.S. have natural immunity.

So with such high levels of protection, why would up to 30% of the population be infected during a potential new wave?

Scientists and public health experts said the 100 million estimate -- based on mathematical models -- does not surprise them and that as immunity wanes and people move indoors due to cold weather, cases will inevitably rise.

"Certainly we're capable of sustaining 100 million infections this winter," Dr. Shira Doron, an infectious disease physician and hospital epidemiologist at Tufts Medical Center in Boston, told ABC News. "The model doesn't mean that there will be 100 million cases, but there is the potential for a lot of infections. It doesn't mean everyone should panic."

Doron explained that even with the high rates of vaccination in the U.S., immunity diminishes over time and COVID-19's ability to mutate has helped it evade -- at least partially -- the protection offered by vaccines.

"Being vaccinated does protect you from serious illness, but it does not [fully] protect you from infection," she said.