This is a significant loss for the Browns as Clowney and Myles Garrett have been a huge factor for how the team runs their defensive scheme. Take away the edges, funnel everything inside, then make the opponent play in a bottleneck.
It causes the interior, including Malik McDowell and Malik Jackson to cover less ground and be more focused on winning inside, rather than worrying about turning and running to deal with perimeter defense.
That becomes more difficult without Clowney. The Browns have Takkarist McKinley, who will likely step into the starting lineup in place of Clowney. They also have Ifeadi Odenigbo, who will likely see significant playing time for the first time this season.
It's possible the Browns linebackers will also be asked to cover more ground, but one option the Browns have used in the past has been bringing down a safety like Ronnie Harrison or Grant Delpit to help seal the edge.
The Chargers offense is challenging both due to the talent at their disposal as well as their scheme. Being down a player like Clowney only increases the difficulty the Browns will have in trying to stop it.
So far, the Browns have gotten high end play from reserve players stepping in and contributing, but it's important to note that this will be the first game the Browns will be missing one of their defensive linemen. Their front has been a massive luxury, so this will be their first test without the entire group available.