Kyrgios had won 15 of his last 16 matches, with his only defeat coming in the Wimbledon final.
As it stands, the CDC's rules state that non-US citizens require proof of vaccination to enter the country. With Djokovic remaining firm on his refusal to get vaccinated, the former world number one looks set to miss the tournament. Just last week, Djokovic's coach Goran Ivanisevic said there was "zero hope" of attending the final Grand Slam of the year in New York.
Casper Ruud is on the brink of a career-best ranking.