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Sen. Roy Blunt (R-Mo.) will not run for re-election in 2022, he announced on Twitter Monday.

Why it matters: The 71-year-old senator is the No. 4-ranking Republican in the Senate, and the fifth GOP senator to announce he will not run for re-election in 2022 as the party faces questions about its post-Trump future.

Sen. Joe Manchin (D-W.Va.), America's ultimate swing voter, told me on "Axios on HBO" that he'll insist Republicans have more of a voice on President Biden's next big package than they did on the COVID stimulus.

The big picture: Manchin said he'll push for tax hikes to pay for Biden's upcoming infrastructure and climate proposal, and will use his Energy Committee chairmanship to force the GOP to confront climate reality.

The verdict from Americans trying to get the COVID vaccine is in: the sign-up websites are awful.

Why it matters: Appointment systems are a vital part of getting Americans vaccinated, but a series of missed opportunities, at every level, left local governments scrambling. And the frustrating, confusing process now carries the risk that some people will simply give up.

Former Minneapolis police officer Derek Chauvin's trial for the murder of George Floyd stands out because it's so rare for officers to face any charges for deadly force — even for actions caught on video. But advocates hope times are changing.

Why it matters: Nearly a year after a video of Floyd's choking death went viral, advocates have pushed through proposals in states and cities to make it easier to hold police officers accountable for excessive force. The plans still face resistance from police unions.

Ripple CEO Brad Garlinghouse tells "Axios on HBO" that if his company loses a lawsuit brought by the SEC, it would put the U.S. cryptocurrency industry at a competitive disadvantage.

Why it matters: Garlinghouse's comments may seem self-serving, but his call for clearer crypto rules is consistent with longstanding entreaties from other industry players.

The COVID Tracking Project, a volunteer group of data analysts, researchers, and journalists brought together by The Atlantic, published its final daily update on Monday — the one-year anniversary of its founding.

Why it matters: The project quickly became a vital resource for news media, academic researchers, and everyday Americans to track COVID-19 cases, hospitalizations, and deaths in the absence of reliable and public data from the federal government.

The imminent enactment of Democrats' $1.9 trillion COVID-19 relief package creates space for lawmakers and the White House to craft infrastructure plans with big climate and energy-related provisions.

Why it matters: President Biden, during the campaign, vowed to make low-carbon energy, climate-resilient infrastructure and transportation projects a big focus of an economic recovery package. And the Texas power crisis could give fresh momentum to investments in grid modernization.

The biggest event for markets this week will be Thursday's meeting of the European Central Bank's governing council and the press conference following it from ECB president Christine Lagarde.

Why it matters: With interest rates jumping around the globe, investors are looking to central bank heads to see if they will follow the lead of Fed chair Jerome Powell, who says rising rates are nothing to worry about, or Bank of Japan governor Haruhiko Kuroda, who has drawn a line in the sand on rates.

The tough task of selecting a jury for former MPD officer Derek Chauvin's trial for the killing of George Floyd is set to begin Monday.

The state of play: "This case may be the most highly publicized criminal trial in a long time. ... That means that it's harder to find people who really have an open mind," Richard Frase, University of Minnesota Law School professor of criminal law, told Axios.

Derek Chauvin, the Minneapolis police officer who was shown kneeling on George Floyd's neck last year in a video that shook the nation, goes on trial this week.

Why it matters: Eight years after the launch of the Black Lives Matter movement, it's still rare for police officers to face legal consequences or jail time over the deaths of Black people. Chauvin's trial will test how that precedent holds up.

President Biden will sign executive orders Monday establishing a Gender Policy Council and directing the Department of Education to review the federal law Title IX, according to administration officials.

Why it matters: The Biden administration is signaling its priorities to advance gender equity and equality as women, particularly women of color, have been disproportionately affected by the COVID-19 pandemic.

Secretary of State Antony Blinken said in a letter outlining a plan to accelerate peace talks with the Taliban that the U.S. is "considering" a full troop withdrawal from Afghanistan, Afghan outlet TOLOnews first reported Sunday.

Why it matters: In the letter to Afghan President Ashraf Ghani, also obtained by Western news outlets, Blinken expresses concern that the Taliban "could make rapid territorial gain" after an American military withdrawal, even with the continuation of U.S. financial aid, as he urges him to embrace his proposal.

Prince Harry and Meghan Markle delivered a devastating indictment of the U.K. royal family in their conversation with Oprah Winfrey: Both said unnamed relatives had expressed concern about what the skin tone of their baby would be. And they accused "the firm" of character assassination and "perpetuating falsehoods."

Why it matters: An institution that thrives on myth now faces harsh reality. The explosive two-hour interview gave an unprecedented, unsparing window into the monarchy: Harry said his father and brother "are trapped," and Markle revealed that the the misery of being a working royal drove her to thoughts of suicide.