President Joe Biden, visibly frustrated by the country’s inability to immunize a reluctant chunk of its population in the fight against COVID, said Thursday that the “time for waiting is over” as he uncorked another round of mandates that now touch many private businesses.

“We have the tools to combat COVID-19,” the president said. “And a distinct minority of Americans supported by a distinct minority of public officials are keeping us from turning the corner.”

The blueprint ordered by the White House requires that employers with more than 100 staffers make sure their workers receive shots or take weekly tests, and it creates a new mandate for federal employees who previously had the option of taking frequent tests instead of getting inoculated.

Biden, who was once reluctant to institute mandates in the vaccine effort, has decidedly changed his tone after the delta variant wreaked havoc in a disappointing second summer of the pandemic.

The president first moved to force federal employees to get shots or undergo regular testing six weeks ago, in what was then viewed as a major escalation in the battle to vaccinate Americans.

But on Thursday he pushed the effort into a new gear, pairing his new plans to push people to get vaccinated with his toughest talk of the pandemic.

In a direct appeal to the holdouts, he said, “We’ve been patient, but our patience is wearing thin, and your refusal has cost all of us.”

Roughly 4 million federal workers, plus millions of contractors, will be required to get vaccinated under an executive order signed by Biden on Thursday. Federal workers who do not get vaccinated will face disciplinary action, according to the White House.

The president’s plan also includes provisions to require vaccinations for workers in most health-care centers that receive Medicare or Medicaid dollars, a move intended to cover more than 17 million workers.

“If you’re seeking care at a health facility, you should be able to know that the people treating you are vaccinated,” Biden said in the State Dining Room of the White House. “Simple. Straightforward. Period.”

At the end of spring, the nation appeared to be on the precipice of winning the war against COVID-19. But coronavirus case rates increased tenfold between the beginning of July and the end of August, hampering the country’s economic recovery and putting a damper on the nation’s health and spirits entering a new school year.

The federal government has struggled to meet its vaccination goals amid misinformation about the shots. Some conservative regions of the country continued to have woeful immunization rates during the summer months, despite desperate bipartisan calls for citizens to get vaccinated.

Almost 1 in 5 Americans over the age 65, who face higher risks from COVID, still were not vaccinated as of Thursday, according to the Centers for Disease Control and Prevention. Overall, about 80 million eligible Americans have so far spurned the shots.

The coronavirus is currently killing about 1,500 people per day in the U.S. The Food and Drug Administration offered full approval to the Pfizer vaccine, offer an additional seal of confidence in the shot.

“What more is there to wait for? What more do you need to see?” Biden said indignantly, leaning over his podium Thursday. “We’ve made vaccinations free, safe and convenient. The vaccine is FDA approved. Over 200 million Americans have gotten at least one shot.”

The most recent jobs report showed American businesses added far fewer new jobs than expected in August. And with workers fretting about pandemic child care and workplace safety, firms cannot fill the millions of job openings they have.

“Our overarching objective here is to reduce the number of unvaccinated Americans,” Jen Psaki, the White House press secretary, said in a briefing ahead of Biden’s speech. “There are of course 80 million unvaccinated Americans at this time. We want to decrease that number.”

Critics have framed vaccination mandates as an infringement on their personal rights, a notion the president pushed back on during his address. He said the issue does not revolve around “personal choice.”

“It’s about protecting yourself and those around you — the people you work with, the people you care about, the people you love,” Biden said in the forceful 27-minute speech. “My job as president is to protect all Americans.”

He said he was directing the Department of Labor to craft an emergency rule that would operationalize his effort to get workers at private businesses vaccinated. That rule, though not an airtight mandate, would reach businesses that collectively employ more than 80 million people.

The White House said it was also working on a rule to ensure that employers offer paid time off to workers covering the time it takes to get vaccinated.

“We’re going to protect vaccinated workers from unvaccinated co-workers,” Biden said.

Top Republicans said the president had gone too far with his latest restrictions and punishments.

“President Biden has made small business an enemy of his administration,” Rep. Kevin McCarthy, R-Calif., the House minority leader, said in a tweet. “Forcing main street to vax or pay a fine will not only crush an economy he’s put on life support — it’s flat-out un-American.”

But Biden framed his moves as an effort to disentangle the nation from a stubborn virus that seemed to be in retreat just weeks ago, when masks were vanishing from coast to coast and the president prematurely announced U.S. “independence” from the pandemic.

On Thursday, he suggested the end is still within reach — if Americans just coalesce behind his vaccination pitch.

“We just have to finish the job,” Biden said, “with truth, with science, with confidence.”