Serena Williams plays a forehand against Harmony Tan during their women's singles first-round match at Wimbledon on June 28, 2022 in London, England. Photo: VCG

Serena Williams tasted bitter defeat on her return to singles tennis at Wimbledon on Tuesday as Rafael Nadal overcame a huge scare to progress to the second round.

Elsewhere on Day 2 of the Championships, title contender Matteo Berrettini was forced to pull out with coronavirus while women's top seed Iga Swiatek extended her winning streak to 36 matches.

Seven-time champion Williams went down to unseeded Harmony Tan of France 7-5, 1-6, 7-6 (10/7) in her first singles encounter since an injury forced her out of her first-round match at Wimbledon last year.

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

"I'm so emotional now," said Tan. "She's a superstar. When I was young, I was watching her so many times on the TV. 

"For my first Wimbledon it's wow - just wow.

"When I saw the draw, I was really scared. She's such a legend. I thought if I can win one game, two games, that would be really good for me."

Williams was far below her imperious best on Tuesday, struggling from the start with her form and fitness.

The 23-time Grand Slam singles champion, cheered by the crowd as she made her entrance, lost the first set but broke early in the second set and went on to level the match.

But she faltered while serving for the match and faded badly in the third-set tiebreaker after taking a 4-0 lead.

She finished with 61 winners but 54 unforced errors the 3-hour, ­11-minute evening match.

Williams brushed off any talk of retirement on Tuesday by insisting she is "motivated" to play at the US Open later this year.

"The US Open was the place where I won my first Slam, it's super-special. There's definitely a lot of motivation to get better and play at home," the 40-year-old American said.

The 23-time major winner, who debuted at the All England Club in 1998, refused to speculate on whether or not she will be back at Wimbledon in 2023.

"I am just playing for right now. I see how I feel and go from there.

"Who knows where I will pop up."

Earlier, an off-key Nadal, already halfway to a calendar Grand Slam after winning the Australian Open and French Open, dug deep to beat Francisco Cerundolo 6-4, 6-3, 3-6, 6-4.

The two-time Wimbledon champion, who has not played at the tournament since 2019, thanked the crowd for their wholehearted support.

Rafael Nadal celebrates a point during his match against Francisco Cerundolo at Wimbledon on June 28, 2022 in London, England. Photo: VCG

"It's not a surface that we play very often, and especially in my case, for different reasons, the past three years I didn't put any foot on a grass court, so it always takes a while," said Nadal, 36. 

"It was my first match and as I know, every day is a test and today was one of these important tests."

The Spaniard appeared to be coasting to victory when he took a two-set lead but his Argentine opponent found a new level, winning the third set and going a break up early in the fourth.

But from 4-2 down the second seed found an extra gear, winning the next four games to seal the match in a little over three and a half hours, roared on by the Center Court crowd.

The 22-time Grand Slam champion played the entire French Open with his troublesome left foot anaesthetized but he has received treatment since then and was moving well on Tuesday.

Canada's Felix Auger-Aliassime, who took Nadal to five sets at the French Open, crashed out of the tournament at the hands of American Maxime Cressy.

The sixth seed lost 6-7 (5/7), 6-4, 7-6 (11/9), 7-6 (7/5), removing another potential obstacle in the path of Nadal, who next faces Lithuania's Ricardas Berankis.

Men's fourth seed Stefanos Tsitsipas beat Swiss qualifier Alexander Ritschard in four sets.

COVID-19 strikes 

The early action at the All England Club was overshadowed by the announcement from Berrettini - last year's runner-up - that coronavirus had forced him out of the tournament.

"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-19 in two days after 2017 runner-up Marin Cilic of Croatia also tested positive.

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

It is business as usual at the Grand Slam this year after the tournament was canceled due to COVID-19 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.

Poland's world No.1 Swiatek, who has won her past six tournaments - coasted into the second round with a routine 6-0, 6-3 victory against Croatian qualifier Jana Fett.

There were also straightforward wins in the women's draw for 2019 champion Simona Halep and fourth seed Paula Badosa.

Beaten French Open finalist Coco Gauff, the 11th seed, recovered from losing the first set against Romania's Elena-Gabriela Ruse to win 2-6, 6-3, 7-5.