John Hunter Hospital has recorded its first coronavirus fatality, a 69-year-old man who died on Thursday.
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NSW Health said the man had likely contracted the virus while interstate but had no known links to anyone else who had tested positive.
Health Minister Brad Hazzard confirmed the man's death during a media conference in Sydney on Friday.
He was the 22nd person to die of COVID-19 complications in NSW and the 53rd in Australia.
"Not just numbers. These are people, people whose families will be missing them today," Mr Hazzard said.
"I just want to say, on behalf of all of the community of NSW and on behalf of the government and all involved, our sincerest sympathies are with your family.
"It won't be an easy time for the family of that 69-year-old, as it hasn't been for the previous 21 people."
The man died in the early hours of Thursday morning.
He is the second Hunter resident to die from COVID-19 complications after a 76-year-old male passenger on the Ruby Princess cruise ship died in Sydney's Westmead Hospital last weekend.
Hunter New England Health officials confirmed three new cases in the district in the 24 hours to 8pm on Thursday, the most recently available statistics.
The district total now stands at 265, including 189 in the five Lower Hunter council areas.
Hunter New England has the highest number of confirmed cases of any region outside Sydney, but South Eastern Sydney (641) and Northern Sydney (506) have much higher counts.
South Eastern Sydney (67) and Northern Sydney (53) also have about twice as many cases per 100,000 people as any other health district.
Hunter New England has 28 cases per 100,000 people, the fifth highest incidence in NSW.
HNEH has conducted 13,831 coronavirus tests, or 1452 per 100,000 residents, the eighth highest testing ratio in the state.
The percentage of positive tests is 1.92 in Hunter New England, slightly below the overall NSW rate.
Nine COVID-19 patients are in HNEH hospitals, including four in intensive care units. The Newcastle Herald understands two of the ICU patients at John Hunter Hospital are gravely ill.
The NSW death toll now stands at 22 and the national toll is 54.
NSW added another 49 cases in the 24 hours to 8pm on Thursday night, taking its tally to 2282.
Twenty-nine COVID-19 patients are in NSW intensive care units, including 23 on ventilators.
The key metric of locally acquired cases with no known source of infection has remained stable in NSW this week at between 400 and 450, a sign that the virus is not yet spreading undetected through the community in large numbers.
The Newcastle and Lake Macquarie local government areas have only five such cases each.
Cessnock's 2325 postcode still has the most confirmed coronavirus cases of any postcode in the Hunter, but the Cessnock local government area has not recorded a new case in more than a week.
Maitland council area (29) has two more cases than it did a week ago, Newcastle (53) has seven more, Lake Macquarie (51) four and Port Stephens (32) three.
The NSW government ordered wider community testing in the "hot spot" of eastern Lake Macquarie this week, but the screening has not yet produced a spike in new cases.
NSW Health said 4444 people had been tested for COVID-19 across the state in the 24 hours to 8pm on Wednesday, a 14 per cent increase from the previous day.
Eleven of the state's confirmed cases are associated with Vista Windows in the Sydney suburb of Preston, including five staff members and six cases linked to them.
The business is now closed.
HNEH will operate testing clinics at John Hunter and Belmont hospitals over the Easter long weekend, but the Mater clinic is closed until Monday.
The Maitland Hospital testing clinic will close on Sunday but be open on Saturday and Monday.
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