The Victorian health department on Wednesday afternoon confirmed two new infections - to be included in Thursday's tally - had been linked to the hotel at Melbourne Airport.

They include a worker and former resident who left on Sunday, the same day as an already known COVID-positive female guest departed.

Her case and that of a food and beverage worker were officially included in Wednesday's tally and come after an authorised officer at the hotel tested positive to the highly-infectious UK strain of the virus last week.

It means the Holiday Inn outbreak now encompasses three workers, two released guests and a family of three who contracted the virus overseas.

The outbreak has forced the hotel's closure, while plans to increase the state's weekly cap on international arrivals from 1120 to 1310 from next week have been put on hold.

Victoria's Chief Health Officer Brett Sutton says authorities suspect the cases are linked to the use of a nebuliser, a device that vaporises medication or liquid into a fine mist.

"If that's breathed in and someone is infectious or later tests positive, then that picks up the virus and then that mist can be suspended in the air with very fine aerosolised particles," he told reporters on Wednesday.

The nebuliser was used by one of the family members, who has an underlying health condition and was taken to intensive care on Tuesday.

Professor Sutton said it was possible everyone on that floor of the hotel had been exposed to the virus.

"The risk with an aerosolised virus is very substantial and so I think we should expect more cases," he said.

COVID-19 Quarantine Victoria Commissioner Emma Cassar said the guest had not reported the nebuliser when arriving at the hotel, and would have been taken to a medi-hotel if they had.

"I'm sure they didn't believe they were doing the wrong thing, but we are taking extra steps to make sure those machines are not in the hotel," Premier Daniel Andrews said.

Mr Andrews said close contacts of the infected workers and guests had been tested and a number of exposure sites had been identified.

He described the emerging mutant strains of COVID-19 as a "very significant cause for concern".

"These hyper-infectious strains are proving very difficult to contain and that's a real challenge," Mr Andrews said.

"We need to redouble our efforts to do more and to respond to that unique challenge."

About 135 staff at the hotel were stood down on Tuesday night and told to get tested and isolate at home for 14 days, bringing the total number of staff isolating to 220.

Forty-eight guests of the hotel considered primary close contacts will be transferred to the Pullman Melbourne.

Any guests who were due to leave quarantine in the next three days will be required to stay at least another three days.

In January, Brisbane's Hotel Grand Chancellor was evacuated after a cleaner tested positive to the UK strain. Returned travellers were moved to another hotel to restart their 14-day quarantine period.

There have been seven cases of COVID-19 transmission across three Victorian quarantine hotels within a week, with three confirmed to be the more infectious UK strain.

Australian Medical Association national president Omar Khorshid said the UK strain had "blown open cracks" in hotel quarantine infection controls, exposing the need for urgent action.

"We are incredibly lucky to have not yet seen a mass outbreak," Dr Khorshid said.

More than 950 hotel quarantine staff across the state are isolating.

Australian Associated Press