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Sinner won 88 per cent of his first serve points and thumped 15 winners to capture the title in South Florida after finishing as the runner-up in 2021 and 2023.
Croatia's Borna Coric, Grigor Dimitrov of Bulgaria and Viktor Troicki had previously tested positive after playing in Djokovic's Adria Tour exhibition tournament in the Balkan region.
Grigor Dimitrov and Borna Coric tested positive for COVID-19 while participating in Novak Djokovic's Adria Tour exhibition tournament.
Dimitrov was one of the players who took part in the Adria Tour with the likes Novak Djokovic, Alexander Zverev and Dominic Thiem among others.
World No. 3 Dominic Thiem of Austria and Bulgarian Grigor Dimitrov, who is ranked 19, have confirmed their participation in the eight-man event.
The two-time tournament champion will be the favourite to claim his third Acapulco title when he faces unseeded Taylor Fritz in the final.
World No. 2 Rafael Nadal remained on course for his third ATP Mexico Open title.
The win sends Medvedev through to his fourth straight final and stretches his win streak to 12 matches.
The win followed the victory for Wawrinka's girlfriend Donna Vekic, who demolished fourth seed Sloane Stephens, earlier in the day.