Covid: Regional rules 'probably going to get tougher', says Boris Johnson
Boris Johnson told the BBC stronger measures may be required in parts of the country in the coming weeks.
He said this included the possibility of keeping schools closed, although this is not "something we want to do".
But he added ministers had to be "realistic" about the spread of the new variant of the virus.
Mr Johnson said the government was "entirely reconciled to doing what it takes to get the virus down" and warned of a "tough period ahead".
He said increasing vaccination would provide a way out of restrictions and that he hoped "tens of millions" would be vaccinated in the next three months.
Speaking on BBC One's Andrew Marr Show, Mr Johnson said he stuck by his previous prediction that the situation would be better by the spring.
But he added: "It may be that we need to do things in the next few weeks that will be tougher in many parts of the country. I'm fully, fully reconciled to that."
"And I bet the people of this country are reconciled to that because, until the vaccine really comes on stream in a massive way, we're fighting this virus with the same set of tools."
He added that ministers had taken "every reasonable step that we reasonably could" to prepare for winter, but "could not have reasonably predicted" the new, more transmissible variant of the virus that has emerged over the autumn.
The prime minister also defended plans for primary schools to reopen in most of England on Monday, amid opposition from teaching unions and some local councils.
Primaries will stay closed to most pupils until 18 January in London and some surrounding areas, but are due to reopen in other areas of England from next week.
The country's secondary schools are due to stagger their return - with pupils due to take exams this year asked to return on 11 January, and other year groups returning in person on 18 January.
Mr Johnson said it was sensible for primaries to reopen in a "large majority" of England and there was "no doubt in my mind that schools are safe".
Unions are telling primary school staff it is unsafe to return to work and are calling for remote learning to be introduced across all primary schools.
However Amanda Spielman, the head of Ofsted, England's schools watchdog, said closures should be kept to an "absolute minimum".