Um ano após a morte de seu amigo e parceiro Sherlock Holmes nas mãos de Moriarty, o Dr. John Watson retoma sua carreira médica como chefe de uma clínica dedicada ao tratamento de doenças raras. No entanto, ele logo descobre que sua antiga vida ainda não terminou com ele.
Watson and the fellows spring back into action when Mary’s mother accidentally poisons herself while suffering from a rare form of dementia that is progressing with impossible speed. Meanwhile, Sherlock Holmes resurfaces after being presumed dead.
A microbiology researcher returns from an expedition to Siberia, leading to a possible outbreak of a revived pathogen. Watson reconnects with Sherlock Holmes.
Watson and the team jump into action when four new patients are brought to UHOP with wounds that appear to be infected with a flesh-eating bacterium following a tornado. Meanwhile, Shinwell searches for meaning as a nursing student and Adam’s wedding to Lauren risks being halted.
While visiting another hospital, Watson becomes convinced that a coma patient is suffering from locked-in syndrome and has been mistaken for a coma patient for over a decade. After the patient is transferred to UHOP for treatment, he shocks the team with chilling messages. Meanwhile, Sherlock is back in town and is staying with Watson.
Watson and the fellows race against time to save the life of Xavier, a 21-year-old athlete with a fast-growing, seemingly incurable cancer. Meanwhile, Mycroft Holmes lets Watson know his team’s work at UHOP may no longer have funding available.
Watson's father, Hamish, visits UHOP to introduce Watson and the fellows to his protégé, Annabelle, a saxophone prodigy with musically induced blackouts. As Annabelle's condition worsens, Watson must confront his long-standing tensions with his father in order to save her.
UHOP veers into terror when Watson and the fellows are taken hostage by a man with a bomb strapped to his chest who is desperate to find a cure for his 9-year-old daughter’s illness.
Watson’s biohacker friend Hobie returns when he rushes his new girlfriend to the Holmes Clinic after they partake in a gene-editing experiment that goes wrong. Meanwhile, Watson becomes suspicious of Sherlock.
Watson and the fellows race against the clock to save a man and his pregnant wife from a terrifying sinkhole. Meanwhile, Ingrid’s future with her therapy group becomes unclear.
When a patient arrives at the Holmes Clinic plagued by a mysterious neurological disorder, Watson and the fellows discover they were forced to eat their parents amid a childhood survival incident. Meanwhile, Adam is struggling with how his future will change as a father.
Watson and the fellows fight to revive a 30-year-old woman, Audrey, after her heart inexplicably stops repeatedly until they discover she has a rare phenomenon called Lazarus syndrome. As these revivals continue, she uses the short window of time available to right her greatest wrong.
Watson and the fellows race to save the life of a young woman who needs a lifesaving kidney donation. Meanwhile, Sherlock returns to help crack unsolved cases in Pittsburgh.
Watson investigates a case involving a mentally unstable mother, with the woman's delusions serving as a mirror to his own newly discovered hallucinations.
In the wake of the car accident, Watson and Laila lie injured and awaiting rescue as the team races to find them before it’s too late. Meanwhile, in a state between life and death, Watson’s mind plays out a modern-day investigation of a case that has long haunted him.
Following his brain tumor diagnosis, Watson goes on medical leave to seek treatment, leaving Mary in charge of The Holmes Clinic as a notorious South American dictator demands Watson see to his mysterious autoimmune condition personally. Meanwhile, Ingrid grows more concerned about Beck’s obsession with Sasha.
As Adam's wife goes in for a C-section to deliver triplets, chaos ensues when their OB-GYN passes out in the operating room. Meanwhile, a severe storm detours Watson and Mary's trip to find a renowned doctor to remove Watson's brain tumor.
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