Schefter reported the player is dealing with "significant respiratory issues" as part of a variety of complications resulting from the coronavirus.
The 23-year-old was placed on the reserve/COVID-19 list twice but is now expected to miss the rest of the 2020 season.
Head coach Doug Marrone indicated there were serious issues when Armstead was placed on the COVID-19 list in September.
"I can't put a real timetable on it but he'll be out for a while," Marrone said, per Michael DiRocco of ESPN.
The coronavirus has led to over 224,000 deaths in the United States, according to the Centers for Disease Control and Prevention, although the disease is considered significantly more dangerous for older individuals. The CDC has reported fewer than 1,000 deaths for those under the age of 30 as of Sunday.
The rate of hospitalization is also higher for older individuals.
There were high expectations for Armstead on the field this season, especially after the Jaguars released presumed starter Leonard Fournette before Week 1. Armstead was second among Jaguars running backs last season with 35 carries and 108 rushing yards after being taken in the fourth round of the 2019 draft.
Undrafted rookie James Robinson has become Jacksonville's starting running back in his absence.