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Vice presidential debates are rarely as thrilling as the showdowns between the two people running for commander-in-chief.

But Wednesday’s faceoff between Democratic vice presidential nominee Sen. Kamala Harris and Vice President Mike Pence in Salt Lake City, Utah, is taking on heightened importance.

With 74-year old President Trump and 77-year old Democratic presidential nominee Joe Biden being the oldest standard bearers ever to lead the Democratic and Republican national party tickets, the vice presidential debate was already consequential – with both running mates seen as presidents in waiting.

But with Trump in isolation at the White House -- after spending three days hospitalized at Walter Reed National Military Medical Center after being diagnosed with COVID-19 -- the debate has surged even further in importance.

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“The odds are unfortunately mathematically in favor of one of these two becoming the next president within the next four years,” noted longtime Republican strategist Colin Reed, a veteran of multiple GOP presidential and Senate campaigns.

Mo Elleithee, the founding executive director of Georgetown University's Institute of Politics and Public Service and a Fox News contributor, highlighted that the showdown has taken on “elevated importance.”

“People traditionally don’t make up their mind based on the vice presidential candidates, let alone the vice presidential debate. But given screwball nature of this campaign right now, it is going to be an important data point,” emphasized Elleithee, a senior spokesman for Hillary Clinton’s 2008 presidential campaign who later served as communications director for the Democratic National Committee.

Workers clean protective plastic panels onstage between tables for Vice President Mike Pence and Democratic vice presidential candidate, Sen. Kamala Harris, D-Calif., as preparations take place for the vice presidential debate in Kingsbury Hall at the University of Utah, Tuesday, Oct. 6, 2020, in Salt Lake City. (AP Photo/Patrick Semansky)

Four years ago, then-Indiana governor Pence followed a lackluster performance by Trump at his first of three showdowns with 2016 Democratic presidential nominee Hillary Clinton with a strong showing against Clinton’s running mate, Sen. Tim Kaine of Virginia.

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Fast forward to today and Pence may need a repeat performance, with the president pilloried for his debate performance last week against Biden, and with the latest national polling and surveys in the key battleground states showing the GOP ticket trailing Biden and Harris.

Here are five things to watch for at Wednesday’s showdown between Harris and Pence.

It’s all about COVID

The coronavirus pandemic has been the leading issue in the presidential race since the outbreak swept the nation in February and March. More than 210,000 people in the U.S. have died due to the virus, with the number of confirmed cases across the country reaching nearly 7.5 million.

Over the past seven months, Biden has repeatedly criticized the president -- charging Trump initially downplayed the severity of the outbreak -- and for botching the federal government’s response.

At last week’s debate, Biden charged that “the president has no plan. He hasn’t laid out anything. … He panicked.”

Trump and his campaign have repeatedly pushed back on such criticism, citing among other things the administration's early effort to restrict air travel with China, where the pandemic originated.

With the president contracting COVID-19, the coronavirus has become the dominating issue in the campaign with just four weeks left until Election Day on Nov. 3.

Elleithee said the debate is “going to come down to a simple thing -- and that’s COVID.”

“Kamala Harris, I expect, will likely try to make as much of this debate about COVID and the federal response as she can. The vice president will want to make as much of this debate about anything but COVID as he can,” Elleithee predicted.

Elleithee pointed that that “for Harris, this isn’t just another sparring match between the two campaigns top surrogates because of the vice president’s unique role in the COVID response. He was the head of the White House coronavirus task force, so Harris will likely seize the opportunity to tie him as closely as possible to the president, tie him as closely as possible to the federal government’s response and push him on it.”

Pointing to polling that indicates a majority of Americans think that Biden would do a better job combating the coronavirus than Trump, Elleithee spotlighted that if Harris “can tether Pence to Trump on COVID and turn this debate into a referendum on the federal government’s response to COVID, then she’ll have accomplished what she needs to.”

Changing the conversation

The president’s comments over the past week have given the Democratic ticket more ammunition. Trump -- who avoided wearing a mask in public until July and who continues to resist any forceful urging of Americans to wear masks -- once again mocked Biden for wearing a mask, saying at last week’s presidential debate, “I don’t wear a mask like him. Every time you see him, he’s got a mask. He could be speaking 200 feet away and he shows up with the biggest mask I’ve ever seen.”

And critics are blasting him for seemingly downplaying the virus Monday night after returning to the White House following his release from Walter Reed hospital.

“Don’t let it dominate you. Don’t be afraid of it,” Trump said in a video.

Elleithee argued that “the vice president needs to find ways to take the conversation away from the coronavirus as often as he possibly can. This is not solid ground for him to stand on and it’s been made worse by the president’s response to his own illness.”

Testing messages

The vice presidential faceoff is the first debate since the president’s COVID diagnosis.

That gives the senator from California, who served as San Francisco district attorney and California attorney general before winning election to the Senate in 2016, first dibs in trying to prosecute the coronavirus case against the GOP ticket.

Reed noted that the Democratswant to make this election a referendum on Trump and COVID and Harris is going to get an opportunity to do that before Biden does. So in some ways she’ll have a chance to test some messages in real time to see how they stick and provide Biden a road map when he faces off with Trump again next week.

Spotlight the economy

The president’s repeatedly argued that he built the world’s “greatest economy” before it was flattened by the pandemic, and is uniquely qualified to rebuild it.

Reed says he’ll be looking to see if Pence reinforces that argument and also targets Biden’s economic proposals.

“What I think is lacking in the Republican messaging is prosecuting the economic vision and record put forth by the Biden-Harris ticket because poll after poll after poll – no matter how badly Donald Trump is doing head to head against Biden, he still outpolls him on the messaging of the economy,” Reed emphasized. “I think Pence can do that if he digs into Democratic proposals that people like Bernie Sanders are touting on the campaign trail.”

Play the socialism card

The president and his campaign have labeled Harris a “radical socialist” since Biden named the senator as his running mate in August. And they’ve blasted Biden as being “beholden” to the left wing of his party.

Reed expects Pence to reinforce that argument.

“I think there’s a kind of palpable sense amongst Republicans and those who lean Republican that Joe Biden may not be a socialist but many others in the party are and they think that Joe Biden doesn’t have the strength to stand up to them so I expect Pence to push that line of attack,” he said.

But Elleithee argued that if Pence goes down that path, it’s a “wasted opportunity.”

“They’ve been trying it for months and it hasn’t made dent. If anything, their numbers are sliding,” he stressed.