Boris Johnson has acknowledged frustration over the “complex” easing of England’s coronavirus lockdown.
The PM wrote in the Mail on Sunday that more complicated messages were needed during the next phase of the response and as restrictions changed.
His comments come amid mounting criticism of the way restrictions have been lifted in England.
Greater Manchester mayor Andy Burnham warned the PM risked a “fracturing of national unity” if he ignores regions.
And Labour leader Sir Keir Starmer has blamed Mr Johnson for the way Wales and England have diverged on the easing of lockdown.
In his article, Mr Johnson said that the government was attempting something that has “never had to be done before”.
He also cautioned that, while the UK is “leading the global effort” to find a vaccine, it “might not come to fruition”.
Mr Johnson said he trusted the “good sense of the British people” to observe the new rules and thanked the public for “sticking with us” so far.
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The PM said he understood people “will feel frustrated with some of the new rules”, adding: “We are trying to do something that has never had to be done before – moving the country out of a full lockdown, in a way which is safe and does not risk sacrificing all of your hard work.”
But Mr Burnham said England’s regional mayors had been given no notice that lockdown restrictions were being eased.
Writing in the Observer, he warned that without additional support for the regions, there was a danger of a “second spike” of the disease.
He told BBC Breakfast that “the voice of the English regions isn’t being heard at the moment”, adding that the government has “lost some goodwill” with local authorities in its handling and communication of the lifting of lockdown measures.