"If we layer in travel and large indoor gatherings which we know are drivers of transmission, we expect to see a massive surge on top of an already dire situation," said Dr. John Brownstein, chief innovation officer at Boston Children's Hospital and an ABC News contributor, warning that such a surge could result in a "humanitarian crisis."
Holidays have proven to be a catalyst of COVID-19 spread across the country. Earlier this year, after each summer holiday, the U.S. reported a significant uptick in infection across the country, and experts say Thanksgiving could have all the components of a potentially deadly event.
Prior to Memorial Day in May, the national seven-day average of new cases was hovering around 21,000 new cases a day. Five weeks later, that average had doubled, according to an ABC analysis of data compiled by the COVID Tracking Project.
A similar pattern occurred just over a month later following the Fourth of July weekend. Less than three weeks after Independence Day, the average number of new cases had risen by almost 40%, with nearly 60,000 patients hospitalized.
And after the summer surge began to decline, it was shortly after Labor Day that new cases began to rise again, bringing the country to its latest surge. As the weather got cooler, public health experts who had long warned against large gatherings began sounding the alarm that even small gatherings - particularly those that are indoors, with poor ventilation - could drive COVID-19 transmission.
Since mid-September, the number of daily coronavirus cases has increased by nearly 400%, and now the virus is significantly more widespread than it ever was during the summer.
The national average of daily new cases is now more than 100,000 higher than it was in July and five times higher than it was during the initial peak in April.
In the month of November alone, the U.S. has reported nearly over 3.2 million COVID-19 cases, making it by far the worst month on record for daily cases, with a quarter of the country's total cases.
Cases are rising in all but one state, Hawaii, while current hospitalizations are increasing in 48 states, Washington, D.C., and Puerto Rico.
Daily deaths in the U.S. are up by more than 30% from just last week, with 10,617 deaths recorded over the last seven days -- a rate of approximately one death reported every minute.
In preparation for the potential fallout, the Centers for Disease Control and Prevention released new guidance last week that strongly recommended postponing travel and staying home this year as "the best way to protect yourself and others."
"Celebrating virtually or with the people you live with is the safest choice this Thanksgiving," the CDC said.
Dr. Anthony Fauci, the nation's top infectious disease expert, has been taking to the airwaves, repeatedly advising Americans to limit Thanksgiving gatherings to members of the same household.
"The travel, the congregate setting, not wearing masks -- the chances are that you will see a surge superimposed upon a surge," Fauci warned. "What we're doing now is going to be reflected two, three weeks from now."
This message, to please stay home, has been echoed by governors and local officials across the country.
"We don't really want to see mama at Thanksgiving and bury her by Christmas," Mississippi State Medical Association President Dr. Mark Horne said during a virtual meeting last week.
"This year, if you love someone, it is smarter and better to stay away -- as hard as that is to say and hear," said New York Gov. Andrew Cuomo in a press release. "Because if I had to predict, you're going to see a significant spike post-Thanksgiving."
Massachusetts Gov. Charlie Baker is also advising residents to only gather with members of their own household.
"We are urging everyone to make a difficult choice this Thanksgiving," Baker said during a press conference last week. "We saw what happened in Canada when they had their Thanksgiving in October."
And seven Midwestern governors -- five Democrats and two Republicans -- joined forces in a video and opinion piece in the Washington Post to deliver a bipartisan message urging precautions during the upcoming holiday.
"Think about your last Thanksgiving and the people you were surrounded by," they said. "Picture their faces -- laughing with you, watching football with you or even arguing with you about politics. As hard as it will be to not see them this Thanksgiving, imagine how much harder it would be if their chairs are empty next year."
"We must make short-term sacrifices for our long-term health," the video concluded.
Despite the warnings, millions are still traveling this holiday, with the Transportation Security Administration this past Sunday screening over 1 million people for only the second time since the start of the pandemic.
And while the role of indoor gatherings in viral transmission cannot be fully quantified, experts stress that they greatly contribute to the spread of COVID-19.
"These gatherings are in conditions with poor adherence to social distancing and masking along with suboptimal ventilation," Brownstein said.
Experts also say that travelers getting tested before they head home does not mean they're protected.
"The confusion around testing also means that many false negatives will give an unwarranted sense of security to those asymptomatic cases or cases during the presymptomatic phase," Brownstein said, adding that "because of this significant countrywide population mixing, we expect hospitalizations will cross 100,000 and deaths to approach 300,000 by the end of the year."
But ultimately, for millions of Americans, these COVID-19 numbers are much more than just statistics; they represent family members and friends lost to the virus, who will be missing this holiday.
"I can understand the humans behind those numbers," Brandie Kopsas-Kingsley, an ICU Nurse from IU Health Indianapolis, Indiana, told ABC News. "Every single one of those was a life, and a person that mattered. As we celebrate Thanksgiving, that is an empty chair. And all of us have a great responsibility to quarantine, to stay safe, to not go see others."