The United States on Tuesday surpassed 800,000 COVID-19 deaths during the pandemic, reaching a grim and once unfathomable milestone as the country is experiencing yet another wave of infections amid the holiday season.

To put it into perspective, 800,000 is more than the populations of Seattle and Denver – or the populations of Cleveland and Minneapolis combined.

The U.S. death toll as of Tuesday stood at 800,266, according to data compiled by Johns Hopkins University. The total number of reported cases in the U.S. surpassed the 50 million mark on Monday.

"As we mark the tragic milestone of 800,000 American deaths due to COVID-19, we remember each person and the lives they lived, and we pray for the loved ones left behind," President Joe Biden said in a statement released Tuesday night. "I know what it’s like to stare at an empty chair around the kitchen table, especially during the holiday season, and my heart aches for every family enduring this pain."

The latest seven-day average for daily deaths is 1,146, up 54% from Nov. 27, according to data from the Centers for Disease Control and Prevention. 

Cases overall are up 82% since late October to now nearly 117,000 a day. Forty-five states are reporting increases in infections over the past 14 days, New York Times data says.

The U.S. leads the world in coronavirus deaths. Despite accounting for about 4% of the global population, the country has recorded 15% of the COVID-19 deaths.

And the pace has been accelerating. It took the United States 109 days to go from the 600,000 mark to 700,000 deaths. It only took 75 more days to reach 800,000.

And the worsening death toll comes despite vaccines being available to all Americans 5 years and older. Doctors and health officials say unvaccinated Americans account for the majority of those hospitalized for COVID-19, but waning vaccine effectiveness is also a factor.

The president said that in order to heal, we must not remember those we lost, but "we must also act."

"That’s exactly what we have done over the past 11 months," Biden said. "We stood up a historic vaccination program, and 240 million Americans have stepped up and gotten at least one shot. As a result, we have saved over one million American lives, and spared families in every community across the country the incalculable loss that too many others have suffered."

"Today, more than 200 million Americans are fully vaccinated, and each day, more people are getting boosted than ever before," Biden added. "As we head into the winter and confront a new variant, we must resolve to keep fighting this virus together. This means getting vaccinated and getting your booster shot, and taking other prevention measures, such as masking."

Sixty-one percent of Americans meet the definition of fully vaccinated, but health officials recommend everyone who received their second Pfizer or Moderna shots at least six months ago or their Johnson & Johnson shot two months ago to receive a booster dose.

"The vaccines are safe, effective, free, easy, and our best tool to prevent more loss and pain," Biden said, urging those fully vaccinated get a booster dose.

"If you were fully vaccinated before mid-June, please go get your booster shot as soon as possible," Biden added. "And if you haven’t already — please get yourself and your school-age children vaccinated."

"I urge all Americans: do your patriotic duty to keep our country safe, to protect yourself and those around you, and to honor the memory of all those we have lost," Biden concluded. "Now is the time."

There also are concerns about the new omicron variant, first identified in South Africa. The CDC said Tuesday the delta variant still accounted for 97% of COVID-19 cases in the U.S., but health officials are closely monitoring omicron, which is spreading quickly in some other countries, including South Africa and Britain.

A preliminary analysis of data from South Africa released Tuesday found that the omicron variant appears to cause less severe disease than previous versions of the coronavirus, and the Pfizer vaccine seems to offer less defense against infection from it but still good protection from hospitalization.

Pfizer said last week that early lab results show two doses of its vaccine may not offer sufficient protection against symptomatic COVID-19 from the omicron variant, but that three doses appear to be highly effective.