Matteo Berrettini was forced to pull out of Wimbledon on Tuesday after testing positive for coronavirus as Serena Williams prepared to return to singles tennis after a year away.

Elsewhere on day two of the Championships, Rafael Nadal begins his quest to win the third leg of a potential calendar Grand Slam and women's top seed Iga Swiatek starts her bid for a seventh straight tournament win.

The early action at the All England Club on Tuesday was overshadowed by the announcement from Berrettini -- last year's runner-up -- that he was out of the event.

Serena Williams has won seven Wimbledon singles titles
Serena Williams has won seven Wimbledon singles titles AFP / GLYN KIRK

"I am heartbroken to announce that I need to withdraw from @wimbledon due to a positive COVID-19 test result," the 26-year-old Italian wrote on Instagram.

Berrettini was widely regarded as one of the biggest threats to defending champion Novak Djokovic at Wimbledon, having captured back-to-back grass-court titles in Stuttgart and Queen's.

He is the second man to withdraw from Wimbledon with Covid in two days after 2017 runner-up Marin Cilic of Croatia also tested positive.

Spain's Rafael Nadal is targeting a third Wimbledon title
Spain's Rafael Nadal is targeting a third Wimbledon title AFP / Glyn KIRK

"I have no words to describe the extreme disappointment I feel," eighth-seed Berrettini said in his statement. "The dream is over for this year, but I will be back stronger."

The Italian was a potential semi-final opponent for two-time champion Nadal.

His place in the Wimbledon first round will be taken by Sweden's Elias Ymer, a lucky loser from qualifying.

Iga Swiatek's victory in the French Open final was her 35th consecutive match win
Iga Swiatek's victory in the French Open final was her 35th consecutive match win AFP / Anne-Christine POUJOULAT

Wimbledon has returned to normal this year after the tournament was cancelled due to Covid in 2020 and last year was played in front of reduced crowds.

The All England Club said in a statement that protocols remained in place to minimise the risk of infection.

"We are following UK guidance around assessment and isolation of any potential infectious disease," the statement said.

Italy's Matteo Berrettini has pulled out of Wimbledon after testing positive for coronavirus
Italy's Matteo Berrettini has pulled out of Wimbledon after testing positive for coronavirus AFP / Glyn KIRK

"Our player medical team also continue to wear face masks for any consultation."

The main focus on the show courts on Tuesday will be on seven-time champion Williams, who faces unseeded Harmony Tan of France in her first singles match since an injury forced her to pull out of her first-round match last year.

Bulgaria's Grigor Dimitrov receives help from masked medical staff at Wimbledon
Bulgaria's Grigor Dimitrov receives help from masked medical staff at Wimbledon AFP / SEBASTIEN BOZON

Williams, 40, won the last of her Wimbledon singles titles six years ago but reached the final in 2018 and 2019.

The American, who was given a wildcard for this year's tournament, is stuck on 23 Grand Slam singles wins -- agonisingly one short of Margaret Court's all-time record.

Nadal is halfway to winning all four majors in 2022 after following up his Australian Open triumph by winning his 14th French Open title.

No man has won all the Grand Slams in a single year since Ron Laver in 1969, with Djokovic falling just short last year when he lost in the final of the US Open.

The Spaniard's win at Roland Garros earlier this month took him to 22 Grand Slam singles titles -- two clear of Djokovic and Roger Federer.

Nadal won the most recent of his two Wimbledon titles in 2010, having captured his first with an epic triumph over Federer two years earlier.

There was a question mark over his durability for the two weeks at Wimbledon having played the entire French Open with his troublesome left foot anaesthetised.

The 36-year-old second seed has since undergone a course of radiofrequency stimulation, a treatment aimed at reducing nerve pain in his foot.

"I can walk normal most of the days, almost every single day," said Nadal, who faces Argentina's Francisco Cerundolo in his opening match on Centre Court.

"When I wake up, I don't have this pain that I was having for the last year and a half."

Swiatek's last match was a comprehensive victory against Coco Gauff in the French Open final -- her 35th consecutive win.

Wimbledon will test the Polish top seed's ability to keep the run going. Reaching the fourth round last year was her best performance at the tournament, even though she was junior champion in 2018.

Other players in action in the women's draw include 2019 champion Simona Halep, who is the 16th seed this year, and last year's beaten finalist, Karolina Pliskova.

On the men's side, fourth seed Stefanos Tsitsipas takes on Switzerland's Alexander Ritschard.