Stephania Bell explains that fantasy managers will have to wait and see if Michael Thomas and George Kittle will be able to play in Week 2. (0:59)

SANTA CLARA, Calif. -- The San Francisco 49ers aren't even two full weeks into the 2020 NFL season and their so-called "Legendary Revenge Tour" has taken an unwanted detour.

Cornerback Richard Sherman (calf) and wide receiver Deebo Samuel (foot) are on short-term injured reserve, tight end George Kittle's status for this week is in the air because of a sprained left knee and the 49ers have already suffered a handful of other key injuries dating back to training camp. That's on top of losing the season opener to the Arizona Cardinals.

As they head east this week to begin a two-game road swing against both New York teams with a week at The Greenbrier resort in West Virginia sandwiched in between, it's safe to say the 49ers are already facing the type of adversity that doesn't usually hit teams until much later in the season when normal wear and tear is more apt to set in.

NFL Stadium Rank: 1-28 • From Lambeau Leap to D.C. disaster

• SoFi's huge videoboard targets GenZ

• Raiders ready the 'Death Star'

"It's a challenge, but you always have something like this each year," coach Kyle Shanahan said. "It's hitting us pretty hard right now."

Indeed, the 49ers have been hammered by injuries at a few spots, namely wide receiver, cornerback and center.

In addition to Samuel at receiver, the Niners lost Jalen Hurd (torn ACL) for the season in training camp, veteran Travis Benjamin opted out and Richie James Jr. is dealing with a hamstring injury. Rookie wideout Brandon Aiyuk missed the first game with a hamstring injury, though he's back in the mix and expected to play this week against the Jets, barring a setback.

At center, the team will be without starter Weston Richburg (patellar tendon) for at least the first six games. Backup Ben Garland missed the first game because of an ankle injury, though he is also expected back on Sunday.

Cornerback became the latest position of concern Wednesday when the Niners placed Sherman (strained calf) on IR and cornerbacks Ahkello Witherspoon (concussion protocol) and Jason Verrett (hamstring) did not practice.

The 49ers placed Richard Sherman on injured reserve Wednesday with a strained calf. Photo by MSA/Icon Sportswire

It's a list that even Santa Claus would find arduous to read but is particularly jarring given how early in the season it is.

"Definitely some adversity," running back Jerick McKinnon said. "We’ve got a lot of depth, so when an injury happens, it’s the next guy up. The next guy has to step up, fill in that role and fill in that hole as best he can. Yeah, it’s a little bit of adversity, but this team has been through so much adversity since I even first got here, so it’s nothing new. Just have got to find a way to get the job done."

Indeed, the 49ers must find a way to get the job done, particularly in the next few weeks with winnable games against the Jets, Giants, Philadelphia Eagles and Miami Dolphins. Last season, the Niners found themselves in a similar situation about a quarter of the way through the season when they lost key cogs such as tackles Joe Staley and Mike McGlinchey and fullback Kyle Juszczyk. They survived because little-known players such as Justin Skule, Daniel Brunskill and Ross Dwelley successfully filled the void as they rattled off an 8-0 start before their first loss.

That same type of production will be needed this time from the likes of Witherspoon, who is expected to replace Sherman, Kendrick Bourne, who is still in for Samuel, and others, such as soon-to-be-signed wideout Mohamed Sanu.

"We've dealt with this before," quarterback Jimmy Garoppolo said. "I think every team, you’ve got to deal with your injuries. 'Next man up' mindset, but in the past, you've got to rely on the guys that you can trust. They earn that in practice."

According to linebacker Fred Warner, the Niners have already flushed last week's loss to Arizona and their focus is solely on the Jets. Still, it's hard to put together a game plan when you have so many moving parts. The 49ers know they must move on quickly, and after turning a 4-12 2018 into a 13-3 2019, nobody knows better than the Niners that the distance from a pat on the back to a kick in the rear is a matter of inches.

The good news? If San Francisco can weather this storm, they should get Samuel and Sherman just in time for the meat of the schedule, because the new IR rules allow unlimited players to return after just three weeks.

"It allows you to manage some stuff differently," Shanahan said. "... So, it's a challenge and some stuff is still up in the air, but it's not our first time doing this."