As part of St. Bonaventure hospital's international humanitarian program, the team takes on the case of a young boy from the Congo who has severe congenital heart anomalies. Dr. Neil Melendez has doubts about the safety of the procedure, while Dr. Shaun Murphy works out the best course of action. Meanwhile, Murphy's latest encounter with his neighbor Lea has him confused.

Shaun’s proposed treatment for a homeless patient puts him and Dr. Kalu in Dr. Andrews’ crosshairs. Claire tries to overcome Dr. Melendez’s reluctance to do a risky heart operation. Dr. Glassman faces a difficult decision about his health.

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.

The hospital is still in quarantine as Dr. Shaun Murphy continues to be overwhelmed by the chaos and noise in the emergency room; Dr. Morgan Reznick struggles to keep her patients alive, and Dr. Audrey Lim fights for her life. Meanwhile, Dr. Neil Melendez and Dr. Claire Browne must find a way to complete their patient’s bone marrow transplant, despite the quarantine.

Dr. Claire Brown and the team must face hard truths about what lines they are willing to cross when one of Claire's idols becomes her patient.