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By Lauren Turner
BBC News
Prof Sir Jonathan Van-Tam is leaving his role as England's deputy chief medical officer.
Health Secretary Sajid Javid said it had been "an honour" to work with him, saying he was a "national treasure".
Prof Van-Tam said it had been the "greatest privilege" of his career to have served the UK during the coronavirus pandemic.
He will continue to work for the government until the end of March before taking up a new academic role.
Prof Van-Tam became well-known for his colourful analogies during Downing Street coronavirus briefings, using football metaphors to explain complex science.
The professor said his time in the role had been "the most challenging of my professional career, especially the Covid response," adding: "We all wish Covid had never happened."
He thanked all those he had worked with during the pandemic, including the "countless numbers who work behind the scenes - all of whom have an unrelenting commitment to help and support the British public".
He especially praised chief medical officer Prof Sir Chris Whitty, who in turn applauded Prof Van-Tam's "steadfast support, advice, leadership and commitment". The pair were knighted in the most recent New Year Honours list.
Mr Javid paid tribute to Prof Van-Tam for the "vital role he has played in our vaccination programme".
"JVT's one-of-a-kind approach to communicating science over the past two years has no doubt played a vital role in protecting and reassuring the nation, and made him a national treasure," he said.
Prof Van-Tam, deputy chief medical officer for England since 2017, often appeared alongside Prime Minister Boris Johnson at news briefings, where he caught the public's attention by the way he described coronavirus.
In late 2020 - while describing the early stages of the pandemic - he said "it's clear the away team gave us an absolute battering".
A year later, in November 2021, he warned "the final whistle hasn't blown" in the pandemic, but instead predicted we were in "half time of extra time".
"I love metaphors," he told the BBC in 2020. "I think they bring complex stories to life for people."
Analysis
By Jim Reed, BBC Health reporter
Professor Sir Jonathan Van-Tam is widely seen as one of the effective communicators of this pandemic.
Ministers relied on him to answer complex scientific questions in simple terms - whether at the podium alongside Boris Johnson or directly from young listeners on stations like BBC Radio 1.
His plain-speaking delivery along with his love of sometimes tortured metaphors have made him into something of a cult figure over the last two years.
He often compares the pandemic to a football match - with vaccines like a "70th minute equaliser" or a new variant like "two yellow cards to key players".
That kind of easy connection with the public will be missed by government when he returns to the University of Nottingham.
But it may give Professor Van-Tam more time to get to the Jakeman Community stadium and reignite his 50-year love affair with local team Boston United.
Prof Van-Tam had been on secondment to the Department of Health from the University of Nottingham.
In his new role, he will be pro-vice-chancellor at the university's faculty of medicine and health sciences.
The 57-year-old lives with his wife and two teenage sons near Boston, Lincolnshire. He also has an older daughter.
He has previously worked in the pharmaceutical industry and for the UK Health Protection Agency.
The professor volunteered as a vaccinator to help distribute Covid-19 jabs - which included giving then-health secretary Matt Hancock his first dose last year.