LONDON—U.K. Health Secretary Matt Hancock resigned, causing disruption at the top of the government’s pandemic response as Britain grapples with an upswing in Covid-19 cases caused by the Delta variant.

Mr. Hancock tendered his resignation to Prime Minister Boris Johnson on Saturday, according to an exchange of letters released by Downing Street.

His departure followed allegations of an affair with an aide and the publication of images of the couple together inside the health ministry that were published in the Sun newspaper.

Mr. Hancock, who is married, came under pressure to quit from lawmakers because, in conducting the alleged affair with a woman he had known from their university days, he appeared to have broken social-distancing guidelines that his department enforced.

The main opposition Labour Party also questioned the use of taxpayers’ money to employ a friend of Mr. Hancock’s as a paid part-time adviser to the health ministry.

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