The Greek, once ranked third in the world, has slipped out of the ATP top 10 in recent months to now stand at 12th.
Denmark's Holger Rune fought back from a match point down to reach the Japan Open semi-finals after beating Kei Nishikori 3-6, 6-2, 7-5 on Sunday.
Novak Djokovic moved within four matches of completing the first men's singles calendar-year Grand Slam in 52 years.
US Open: Novak Djokovic most recently stretched his domination over 56th-ranked Nishikori with a quarter-final victory at the Tokyo Olympics.
French Open: Kei Nishikori defeated Karen Khachanov 4-6, 6-2, 2-6, 6-4, 6-4 in a marathon five-setter to move into the third round.
Japanese tennis players Kei Nishikori and Naomi Osaka agreed that discussions were needed to ensure a safe organisation of the delayed 2020 Tokyo Olympic Games in the middle of a coronavirus scare in Japan.
Forty-seven players were barred from practising for a fortnight Saturday in a major setback to their Australian Open preparations after passengers on two charter flights that brought them to Melbourne tested positive to Covid-19.
Japan's Naomi Osaka beat Victoria Azarenka 1-6, 6-3, 6-3 in the final to add to winning the 2018 US Open and the 2019 Australian Open.
Japan's Kei Nishikori, the 2014 US Open runner-up, said Sunday he has contracted COVID-19 and has withdrawn from an ATP event in New York with this year's US Open only two weeks away.
Kei Nishikori, who has slipped to 13, said he was disappointed not to be able to begin his season as hoped for in January.