Parts of the Hunter could have only half of adults fully vaccinated by the time NSW starts opening up, and the region's indigenous population is even more vulnerable.
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The government is under pressure to protect areas with low vaccination rates when it starts easing COVID restrictions next month.
"We're terrified of what happens when you open up Sydney and COVID runs through the community," Upper Hunter Nationals MP Dave Layzell said.
An analysis of vaccination data shows the double-dose rate across the Hunter is growing by about five percentage points a week.
Only 26.6 per cent of the Hunter's 20,000 indigenous people aged 15 and over is fully vaccinated.
By October 11, a possible opening date for the fully vaccinated in NSW, about 45 per cent will have received two doses.
Muswellbrook, Singleton and Cessnock, which now have full vaccination rates in the mid-30s, will be just below or just above 50 per cent by October 11.
Muswellbrook has the lowest double-dose vaccination rate of any LGA in the state at 34.1 per cent, a figure growing by only 4.3 percentage points a week.
At that rate, it will have only 47 per cent of adults fully vaccinated by October 11 and will not reach 70 per cent until November 15.
Maitland's rollout is a fortnight behind the NSW rate, and Lake Macquarie and Newcastle are a week behind.
Mr Layzell said sharply rising first-dose rates in some problem areas suggested their second-dose rates would also jump in coming weeks, but they would remain significantly behind the state average.
"Most of regional NSW is feeling vulnerable," he said.
NSW as a whole has 53 per cent full vaccination and parts of Sydney already have double-dose rates above 70 per cent, the government's first target for relaxing pandemic restrictions.
The government has said it will resume regional travel for the vaccinated when the overall state hits 70 per cent coverage, but vaccinated city dwellers and their unvaccinated children could pose a risk to relatively unprotected regions who have seen doses prioritised to Sydney.
Mr Layzell said one solution could be to quarantine parts of the Hunter from Sydney for several weeks until vaccination rates caught up.
He said coastal areas such as Port Stephens which have relatively high vaccine coverage and rely on tourism could be opened to visitors.
Cessnock MP Clayton Barr preferred a blanket ban on Sydney people travelling to regions until mid-November.
"How do you keep people protected under any model, but that would be a really good starting point," he said.
Hunter New England Health added 18 new cases on Tuesday, including eight in Lake Macquarie, five in Newcastle, two in Maitland, one in Cessnock, one in Muswellbrook and one in Glen Innes.
Mr Layzell said the new case in Muswellbrook was unlikely to send the town back into lockdown "at this stage" as the person had not been infectious in the community.
NSW reported 1022 new locally acquired cases of COVID-19 on Tuesday and 10 deaths.
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