There are multiple ways for something to be labelled a class-S threat.
High level duplicators and villains who operate to any exponential degree are automatically considered S-class if their powers generate more instances of power generation or recurring effect in an epidemic pattern.
According to Miss Militia, the difference in response to a class A crisis and a class S one is minor. Some tertiary protocols change, the Triumvirate are guaranteed to assist, and there are penalties for anyone who subscribed to the critical situation roster if they sit it out.
There are epidemic protocols for dealing with a Class S situation.
At the beginning of the story, there were six recognized class S threats.
- The Simurgh
- The Slaughterhouse Nine (collectively)
The above emerged as class S threats over the course of the story. Further, Ash Beast has the potential of being an S-class threat but moves slowly enough to be avoidable, and Blasto had a "high risk" of becoming S-class.
There were threats of a similar level that were not widely known, and were dealt with by organisations such as the Thanda. Some tinkers such as, Bonesaw, Jamestowner, Monstrum, Mosaic, and Rattenfänger, have the potential for becoming S-class threats.