Victoria's chief health officer Brett Sutton said the "working hypothesis" was at least three cases were related to an exposure event involving a nebuliser.
"It vaporises medication, or liquid, into a very fine mist," Professor Sutton said.
"The virus was carried out into the corridor and exposed the authorised officer, the food and beverage service worker, and also the other resident."
He said it meant everyone who was on that floor might have been exposed to the virus and warned there could be more cases.
Premier Daniel Andrews said any worker or resident who spent 15 minutes or more at the Holiday Inn between January 27 and February 9 was considered a close contact and must isolate for 14 days.
"This is a wicked enemy, made more challenging by the fact that it is changing, it is a moving target," Mr Andrews said.
"These mutant strains are highly infectious, hyper-infectious, really."