Boris Johnson has said he is "deeply sorry" for every life lost to coronavirus as he insisted the Government did "everything we could" to minimise deaths and suffering.
The Prime Minister offered his "deepest condolences" to those whose relatives have died of Covid-19, and pledged to ensure their loved ones are remembered.
His comments came as the Government's figure for coronavirus deaths passed 100,000 – though separate data published by statistics agencies places the toll at 115,000.
Mr Johnson said: "I think on this day I should just really repeat that I am deeply sorry for every life that has been lost and of course as I was Prime Minister I take full responsibility for everything that the Government has done.
"What I can tell you is that we truly did everything we could, and continue to do everything that we can, to minimise loss of life and to minimise suffering in what has been a very, very difficult stage...
"And a very, very difficult crisis for our country, and we will continue to do that, just as every government that is affected by this crisis around the world is continuing to do the same."
Referring to the 100,000 deaths, Mr Johnson said it was "hard to compute the sorrow contained in that grim statistic: the years of life lost, the family gatherings not attended and for so many relatives the missed chance to even say goodbye".
He told a Downing Street press conference that "you would exhaust the thesaurus of misery" in trying to describe the figure, adding: "It's an appalling and tragic loss of life, there's no question about it."
England's chief medical officer Professor Chris Whitty braced the country for "a lot more deaths over the next few weeks before the effects of the vaccines begin to be felt".
He said the number of people testing positive for coronavirus was "still at a very high number, but it has been coming down".
Prof Whitty also cautioned against relaxing restrictions "too early" as he said Office for National Statistics data demonstrates a slower decrease.
The number of people in hospital with Covid-19 in the UK was still an "incredibly high number", he stressed, and "substantially above the peak in April".
Prof Whitty said it looked like hospital figures were coming down slightly in areas such as London and the South East and the East of England, but in some areas levels were "still not convincingly reducing".
Sir Simon Stevens, chief executive of NHS England, said that more than a quarter of a million severely ill coronavirus patients have been looked after in hospital this year.
"This is not a year that anybody is going to want to remember nor is it a year that across the health service any of us will ever forget," he said.
He also told the briefing that there will be an end to the "incessant" new Covid-19 admissions to hospitals.
"What people (health staff) probably want right now is three things – first of all to be able to look forward to some sort of respite from what has been an incredibly demanding and continuous year of pressure.
"Secondly to know that there are reinforcements on the way, that the staffing pressures in the health service will be taken seriously in the years to come.
"And thirdly to tackle the pressures in the here and now which fundamentally are about reducing the number of new patients who turn up in A&E severely ill with coronavirus day in day out.
"So it's that combination I think. The sense there will be some respite, the sense the health service will get resilient, staffing support it needs in the years to come, but right now we actually collectively turn off the incessant new admissions that are arriving with very severely ill coronavirus patients."
Labour leader Sir Keir Starmer said the 100,000 death toll was a "national tragedy".
He added: "We must never become numb to these numbers or treat them as just statistics. Every death is a loved one, a friend, a neighbour, a partner or a colleague. It is an empty chair at the dinner table."
In other developments:
– The Government said that, as of 9am on Tuesday, there had been a further 20,089 lab-confirmed cases of coronavirus in the UK.
– More than 6.8 million coronavirus vaccinations have taken place in the UK as of Monday – a rise of 279,757 on the previous day's figures.
– Analysis of official data by the PA news agency showed care home residents have accounted for almost a third of the total number of coronavirus deaths in England and Wales.
– The Office for National Statistics revealed the unemployment rate reached 5% in the three months to November for the first time since early 2016 after another 202,000 people lost their jobs.
– Vaccines minister Nadhim Zahawi said he was "confident" that the Pfizer vaccine supply would continue – despite the European Union threatening to impose tight controls on the export of coronavirus jabs made in the bloc.
Meanwhile the Government looks set to announce plans on Wednesday to make passengers arriving in England from high-risk coronavirus hotspots quarantine in hotels.
Home Secretary Priti Patel will give a statement to MPs on Wednesday afternoon on health measures at the border.
She told the Commons on Tuesday that the Government "will not hesitate to take further action" to protect the UK from new strains, and said "measures are always under review".
The Prime Minister was due to discuss the proposals – designed to ensure people follow self-isolation rules – with senior ministers at the "Covid Operations" committee on Tuesday.