Dr. Shaun Murphy and Dr. Alex Park treat two patients who collapse at the local airport and whose symptoms point to an infection that may become airborne. The staff races to contain the infection before it spreads to the rest of the patients in the ER, resulting in a hospital quarantine during the holidays.

In the aftermath of the quarantine, the staff of San Jose St. Bonaventure Hospital tries to return to their normal routines as the Department of Public Health office decides they need to review what transpired to restore public confidence. Meanwhile, as Dr. Audrey Lim recovers from the virus, she and Dr. Neil Melendez navigate their new personal and working relationship, while Dr. Shaun Murphy and Dr. Aaron Glassman try to relax and visit Lea at work.