NEW YORK — This theater game was in deadly earnest. In a midtown Manhattan rehearsal room, Blythe Adamson laid out five color-coded index cards for the cast and backstage crew of "Pass Over," which starts Broadway performances Wednesday. A green card said "PCR Negative," indicating a negative coronavirus test. An amber card said "Exposed!"; a red one, "PCR Positive," and so on.

Drawing the cards from paper bags, the production team gamed out all of the possible covid scenarios with Adamson, a highly regarded infectious-disease epidemiologist and economist. She has been retained by the play’s producers to instruct the company and train stage managers as covid safety officers — in service of putting on a show seven times a week in the midst of a mutating pandemic.

One of the actors, Jon Michael Hill, immediately pulled out a red card, according to Matt Ross, the show’s lead producer: If it happened in real life, he’d have to be quarantined. “I don’t think I like this game,” Ross wryly told the room.

These are trying and uncertain times for Broadway and the rest of American theater, an industry in which the majority of workers have been denied employment for a year and a half. Now, as productions here and across the country seek paths back to stable runs with live audiences, “Pass Over” is taking aggressive and painstaking measures to protect staff and spectators. For the theater, playing it safe has never been a more meaningful directive.

“The question is, ‘How much are you willing to enact to avoid canceling a show?’ ” said Adamson, whose pandemic consultancy, Infectious Economics, has helped develop protocols for the NBA, the fashion industry and retail stores.

“One of the most important things we can have is a fully vaccinated cast and crew,” she said. “This greatly reduces the possibility that there will be a transmission. Second is routinely testing all of the cast and crew with high-quality PCR tests.” (PCR stands for polymerase chain reaction test, considered far more reliable than, for example, the less expensive rapid antigen test.)

With coronavirus cases spiking again — because of the spread of the delta variant and a resistance to being vaccinated by a considerable subset of Americans — theaters on, off and well beyond Broadway are examining how to respond.

“Springsteen on Broadway,” which began at the St. James Theatre on June 26, and the three-actor “Pass Over” have made proof of vaccination mandatory for audiences. On Thursday, Actors’ Equity, the union representing 51,000 actors and stage managers, announced new protocols requiring vaccinations for its workforce on Broadway and in touring shows that have standalone runs in other cities. This significantly affects producers and owners of the 41 Broadway theaters, where more than 40 productions are planned for the 2021-22 season. On Sept. 2, the musicals “Waitress” and “Hadestown” begin performances, the first large-cast shows to return.

No problems have been reported by “Springsteen,” but setbacks have occurred this summer for other productions. Shakespeare in the Park’s “Merry Wives,” an adaptation by Jocelyn Bioh of “The Merry Wives of Windsor,” had to cancel three performances in July after a member of the production tested positive for covid; it resumed July 24. The Public Theater, the show’s producer, tests company and crew, but does not require vaccinations. Asked about the “Merry Wives’ ” immunization policy, spokeswoman Laura Rigby emailed: “For this summer production, we are strongly encouraging but do not require vaccination for company or crew.”

Health experts say that there is a crucial distinction between encouraging and mandating vaccinations — and that the requirement should be an industry standard.

“That would set an example,” said Saad B. Omer, an authority on vaccination and director of the Yale Institute for Global Health. A self-described theater enthusiast, Omer said that certifying vaccination for everyone in a theater — as well as keeping a mask on — should be universal priorities.

“These are things that you should ensure proactively and now, so that everyone can remain safe,” he said, adding that he has a personal stake in seeing the practices become compulsory: “I have tickets to ‘Hamilton’ in October.”

Unions such as Actors’ Equity have already developed voluminous guidelines for companies requiring full vaccination and regular testing for those that do not. But Matt Ross, a theater publicist moving increasingly into producing (he will also bring Lucas Hnath’s “Dana H.” and Tina Satter’s “Is This a Room” into rotating rep on Broadway this fall) is setting his own exacting safety code with “Pass Over.”

“Our cast needs to be and feel safe,” Ross said in an interview with Adamson, conducted maskless outdoors. Last year, he and several others in the field established the Covid Theatre Think-Tank as a clearinghouse for developments in covid research and mitigation practices. The experience gave him a sophisticated notion of what would be required for a health-conscious run in a Broadway theater. Most of Broadway’s houses are operational antiques, with age-old ventilation systems, narrow backstages and suites of dressing rooms that resemble rabbit warrens.

After Adamson was hired, she and Ross climbed onto the theater roof to check out ventilation fans and key in on other fixes that would make the August Wilson Theatre safer. A checklist evolved — “To make sure,” Adamson said, “every window is open that is supposed to be open; to make sure every fan is turned on; to make sure every HEPA [purifying] filter is what is should be.” In one instance, Ross said, Adamson discovered an exhaust fan in a backstage bathroom; with the door open, that device became yet another way to increase the flow of fresh air.

With Adamson’s input, a covid-testing regimen was instituted. In response to the pandemic resurgence, she recently increased testing of 50 company and crew members from two to three times a week. The saliva tests are couriered to Brooklyn’s Mirimus Clinical Labs, where they are tested collectively. If the “pooling test” result is positive, the lab then tests each sample individually, to isolate the source. The process costs a few hundred dollars each time, Ross said.

For “Pass Over,” a “Waiting for Godot”-like tale by Antoinette Chinonye Nwandu about young Black men in a violence-racked city, Ross has hired an extra understudy in case any actor is sidelined. The production and the playhouse, owned by Jujamcyn Theaters, both have covid safety officers on-site; “Pass Over’s” 0fficer, stage manager Pam Remler, has been sending a report to Adamson every day during rehearsals.

Audiences will have to produce proof of vaccination — or in cases of religious or medical issues, a negative coronavirus test result within 72 hours of the performance. Inside the August Wilson, masks will have to be worn when entering or moving about. But seated patrons will have the option of removing them. “Springsteen on Broadway” has no mask mandate.

Of course, with a pandemic still raging in some places, the rules can change. “We are very flexible,” Adamson said, adding that the renewal of mask-wearing recommendations by the Centers for Disease Control and Prevention comport with the production’s strategies.

“One of the ways to interpret the CDC’s guidance is the emphasis on the importance of wearing masks indoors when the vaccination status of the people around you is uncertain,” she said. “The current planned approach for ‘Pass Over’ is that confirmation of vaccination status is an important element in ensuring that the probability of there being an infectious person indoors will be much, much lower.”

At our initial interview, Adamson pulled out her covid index cards, and we played a round. I drew a green card: It would be safe for me and the show to go on. Which is the turn of the plot that Ross and company are counting on.

“I believe,” Ross said, “that we will have the tools to do the play and welcome audiences — and to minimize and manage the risks. All I can do is do my best to keep people safe.”