In the past nine months, Jimmy Garoppolo nearly led San Francisco to the Super Bowl, had surgery on his throwing shoulder, lost his job to Trey Lance and was shopped to other teams before the 49ers reworked his contract to be the backup.

That role lasted a little more than one game.

With Lance out for the season following surgery on his right ankle on Monday, Garoppolo is the No. 1 quarterback once again, and he makes his first start of the season on Sunday night when San Francisco (1-1) pays a visit to the Denver Broncos (1-1).

Garoppolo has appeared unfazed by everything that has happened over the last 18 months, and overlooked in all of what has happened is that he is 35-16 (including playoffs) as the 49ers' starting quarterback.

"He is just like that in every situation since we met him," San Francisco head coach Kyle Shanahan said. "He tries to simplify things and not get caught up in all that stuff. He communicates with us. It's why guys love him, and we all do."

The 49ers have been hit with significant injuries in each of their first two games. In the opener, a loss at Chicago, running back Elijah Mitchell went down with a knee injury and was placed on injured reserve, and then Lance suffered a fractured ankle against the Seattle Seahawks.

With Lance out, San Francisco will need to adjust the offense to fit Garoppolo's skillset, which means wide receiver Deebo Samuel will likely be used in the same way he was last year -- as a dual threat as a pass catcher and a rusher.

Garoppolo's first start of the year comes against a Denver defense that has held its first two opponents to a total of 26 points. The Broncos have just one takeaway, but they've held Seattle and Houston to just two touchdowns -- both by the Seahawks.

The area of concern is the offense, which has been plagued by inefficiency and questionable decisions by first-year head coach Nathaniel Hackett. Denver has already been penalized four times for delay of game and burned all of their second-half timeouts with 7:38 left in the 16-9 win over the Texans.

"We've got to make sure the communication is clear and concise," Hackett said. "I need to do better making decisions, faster and quicker and getting that information to the quarterback ... It's got to improve."

The Broncos also need to improve the overall efficiency of the offense. Russell Wilson was brought in to shore up the quarterback position, but the offense has produced just 32 points in two games. The depth at wide receiver took a hit when Tim Patrick went down with a torn ACL in the preseason, and Jerry Jeudy is dealing with a rib injury that has him listed as day-to-day.

Denver got some good news on the defensive side. Linebacker Josey Jewell, who has missed the first two games with a calf injury, practiced Wednesday, and the shoulder injury cornerback Patrick Surtain II sustained against the Texans is not serious.

The good news for the 49ers is that tight end George Kittle practiced to start the week and could make his season debut on Sunday night. Kittle has missed the first two games of the season with a groin injury.