WASHINGTON — The Senate on Wednesday voted 52 to 48 to confirm Rachel Levine as the nation’s assistant secretary for health, making her the highest-ranking openly transgender official in U.S. history.

All Democrats and independents voted to support Levine, with Republican Sens. Susan Collins of Maine and Lisa Murkowski of Alaska crossing the aisle to support her, prompting cheers from advocates who called the vote a breakthrough.

“I firmly believe that turning points, such as today’s Senate confirmation vote for Dr. Levine’s appointment, are powerful indications that this nation is truly heading down the pathway to lasting transgender equality,” said Raffi Freedman-Gurspan, who served in the Obama administration and was the first openly transgender official to work in the White House.

Levine, who most recently served as Pennsylvania’s top health official, is the first openly transgender official to be confirmed by the Senate. Her candidacy was widely opposed by religious-rights groups, and some Republican critics also zeroed in on gaps in Pennsylvania’s nursing home data that they said complicated the state’s response to the pandemic.

The assistant secretary for health oversees a broad portfolio of public-health initiatives, and President Joe Biden has said that Levine will play a key role in the nation’s coronavirus response. The Trump administration’s assistant secretary for health, Brett Giroir, served as the nation’s coronavirus testing czar.

The assistant secretary for health also oversees the surgeon general, Vivek Murthy, who was confirmed Tuesday.

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LGBTQ advocacy organizations applauded the vote, with many advocates having viewed Levine’s candidacy as a symbolic victory amid efforts to ban or restrict treatments for transgender youth.

“With the confirmation of Dr. Rachel Levine, we are one step closer to a government that mirrors the beautiful diversity of its people,” Alphonso David, president of the Human Rights Campaign, said in a statement.

Levine, 63, was first appointed as Pennsylvania’s physician general in January 2015 and became the state’s health secretary in 2017. She previously served in senior medical positions at the Penn State Milton S. Hershey Medical Center.

Levine was a target of online attacks as her profile rose during the pandemic, and Sen. Rand Paul, R-Ky., lashed out at Levine last month at a Senate Health, Education, Labor and Pensions committee hearing, questioning her support of hormone therapy for minors. Advocacy organizations and public health experts condemned Paul’s questions as harmful misrepresentations, and Paul’s Democratic colleagues rebuked him for the remarks.

The Senate last week also confirmed Xavier Becerra as HHS secretary in a narrow 50 to 49 vote, but numerous senior positions in the health department remain open. Biden has not nominated a commissioner for the Food and Drug Administration, and the Senate has yet to hold its first confirmation hearing for Chiquita Brooks-LaSure, whom Biden selected to lead the Centers for Medicare and Medicaid Services.

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The Washington Post’s Samantha Schmidt contributed to this report.