In addition, Richard Flood and Anthony Hill, who both appeared in the sixteenth season in recurring and guest capacities, respectively, received promotions to the main cast.

Meanwhile, main cast members Giacomo Gianniotti, Jesse Williams, and Greg Germann all departed the series during the season.

Nearly every main storyline in the season centered around the COVID-19 pandemic, with a number of plot points also connecting to spin-off series Station 19 through fictional crossover events.

[60] To limit the spread of COVID-19, cast and crew members only worked ten-hour days compared to the usual twelve hours.

[63] Vernoff said that face masks were worn by all cast and crew members while not filming, including between takes and during rehearsals, and that speaking was not allowed in the hair and makeup trailer.

[62] Cast members carried their own makeup bags to do last-minute touch-ups, and different camera lenses were used to make people standing far apart appear closer together.

[65] In March 2021, Deadline Hollywood reported that another spin-off series was in the works following an interview with ABC Entertainment President Craig Erwich.

[67] Despite an initial uncertain future from Vernoff,[68] Pompeo,[69] and network executives,[70] the series was renewed for an eighteenth season.

[71] Kim Raver, Camilla Luddington, and Kevin McKidd each signed a three-year contract in July 2020, keeping them attached to the series through a potential nineteenth season to portray Dr. Teddy Altman, Dr. Jo Wilson, and Dr. Owen Hunt, respectively.

[73] A number of previous series regulars appeared in the season during a storyline revolving around Meredith Grey battling COVID-19 while imagining herself on a beach.

[77][42] Prior to their return, Leigh and Dane last appeared in the eighth-season finale "Flight" and "Remember the Time", the second episode of the ninth season.

[80] Giacomo Gianniotti, who portrayed Dr. Andrew DeLuca, exited the series as a main character after being killed off in "Helplessly Hoping.

[82][83] Greg Germann, who had portrayed Dr. Tom Koracick since the fourteenth season, also departed in "Tradition", being written out in the same storyline as Williams' character.

[49] In addition, Barrett Doss, Jay Hayden, Grey Damon, Danielle Savre, and Okieriete Onaodowan made guest appearances as their Station 19 characters in crossover events.

[50] Lisa Vidal and Melissa DuPrey recurred as a mother-daughter pair named Alma and Sara Ortiz who were part of Grey Sloan's new intern class.

[38][90] Robert I. Mesa was also cast in a recurring role for the season portraying James Chee, the first indigenous doctor on the series.

The conversation became: How do we tell this painful and brutal story that has hit our medical community so intensely and permanently changed medicine?

[92] Zoanne Clack, a medical doctor who serves as a consultant, writer, and executive producer on the series and previously worked for the Centers for Disease Control and Prevention, said that the goal of the season was to accurately show the infection rate and transfer of COVID-19.

[96][97] Bailey's portrayer Chandra Wilson stated that nursing homes, where the character's mother was located, were largely affected by COVID-19 so that when the script was given to her she knew that the experience needed to be told.

[100] One of these finished the story centered around the mental health of Gianniotti's Andrew DeLuca, which was introduced in the sixteenth season, regarding a patient that had been sexually abused and human trafficked.

However, these plans were scrapped when the season was cut short due to the pandemic; Vernoff said that the death would not have been DeLuca because she wanted to show that people could experience a mental health crisis and be successful afterwards.

[115] This episode also aired outside of its regular timeslot due to a programming delay as a result of a presidential address by Joe Biden,[116] and began broadcasting at 9:25 pm ET.

[126] Ani Bundel with NBC Think stated that the season stayed true to the medical community, noting that even though cheerful and funny moments were mixed in, viewers were not able to forget how many people had died.

[127] Alex Cranz from Jezebel felt that the season premiere crossover was "a series of memes ripped straight out of May 2020 instead of November 2020", writing that he would have liked to see the episodes three to four months earlier.

[128] TVLine's Charlie Mason mentioned that the rules of Meredith's beach were confusing because she was able to see people that were both dead and alive, also saying that although it seemed nice at first, it eventually lost its appeal.

[129] Meanwhile, Jack Wilhelmi from Screen Rant said that the return of Patrick Dempsey to the series was a "major mistake";[130] however, Saloni Gajjar of The A.V.

[134] The season was awarded The ReFrame Stamp,[135] a certification given to scripted television productions that hire "women or individuals of other underrepresented gender identities/expressions [...] in four out of eight key roles including writer, director, producer, lead, co-leads, and department heads.