England loose-head prop Ellis Genge has tested positive for Covid-19, meaning uncapped Sale prop Bevan Rodd will start against Australia on Saturday.
Newcastle's Trevor Davison, who earned his only England cap in July, replaces Rodd on the bench.
Joe Marler - who came on for Genge against Tonga last weekend - is out after a positive test on Monday.
Owen Farrell did not play last weekend after a test said he had Covid-19, but it was found to be a false positive.
The RFU said Genge is isolating and that no other positive results have been returned by players or staff after lateral flow tests, with PCR results expected later on Friday or early Saturday morning.
Government regulations require those testing positive to isolate for 10 days, meaning Genge will also miss England's final autumn Test against world champions South Africa.
England's coronavirus issues began when a member of their support staff tested positive on 4 November.
The side trained at Twickenham as planned on Friday morning and head coach Eddie Jones said of the disruption: "We treat it as normal now.
"Every day is an adventure and we're on a bit of a rollercoaster at the moment. Covid keeps coming, we just accept it and get on with it.
"I was watching the players come through this morning. Some are disappointed for Ellis, others are angry, others just want to get on with it."
Davison's call-up comes as experienced England international Mako Vunipola continues to be left out of the squad.
England: Steward; Tuilagi, Slade, Farrell (capt) May; Smith, Youngs; Rodd, George, Sinckler, Itoje, Hill, Lawes, Underhill, Curry.
Replacements: Blamire, Davison, Stuart, Ewels, Dombrandt, Simmonds, Quirke, Malins.