In the first year of the pandemic, at least four people in Michigan were infected with a version of the coronavirus observed mostly in mink, the Centers for Disease Control and Prevention confirmed on Monday.

The cluster, which previously included just three cases, represents the first known instance of possible animal-to-human transmission of the virus in the United States.

Two of the infected were employees of a Michigan mink farm that experienced a coronavirus outbreak in October 2020. The other two had no known links to the farm, suggesting that the mink variant may have been circulating more widely among area residents at the time.

Samples of the virus collected from all four people contained two mutations that scientists have hypothesized may be signs of adaptation to mink, Dr. Casey Barton Behravesh, who directs the C.D.C.’s One Health Office, said in an email on Monday.

The mutations have previously been documented in farmed mink in Europe, as well as in people with connections to those farms.

“This, in addition to the mink farm workers testing positive for Covid-19 after the mink herd had begun experiencing illness and increased mortality, suggests that the most likely hypothesis is that the workers were infected after contact with mink on the farm,” Dr. Barton Behravesh said.

But that cannot be conclusively proved, she noted.

“Because there are few genetic sequences available from the communities around the farm, it is impossible to know for sure whether the mutations came from mink on the farm or were already circulating in the community,” she said.

National Geographic first reported the fourth human case, after obtaining government documents about the mink farm outbreak under the Freedom of Information Act.

Last year, The Detroit Free Press and the Documenting Covid-19 project reported on the first three cases, which included the two farm workers and a taxidermist who had no known connection to the mink farm, according to emails obtained by the two organizations.

On Monday, they reported that the fourth case had been the taxidermist’s wife.

In early October 2020, Michigan officials announced that the virus had been detected in mink on a local farm and that several of the animals had died. Upon the state’s request, the C.D.C. deployed a team to help investigate the outbreak.

The investigators collected samples from animals and human workers on the farm, as well as people in the surrounding community, Dr. Barton Behravesh said. In March 2021, the C.D.C. updated its website to note that a “small number of people” had contracted a version of the virus that “contained unique mink-related mutations.”

“This suggests mink-to-human spread might have occurred,” the agency said, noting that all of the human patients had recovered.

But the first human cases, in two workers on the affected mink farm, were identified as early as Nov. 4, months before the agency updated its website, National Geographic reported.

“C.D.C. became aware of genetic sequencing data indicating possible mink-to-human transmission in late 2020,” Dr. Barton Behravesh said.

The agency then worked with other federal and state officials to analyze that data, she added: “Information was published on the C.D.C. website as soon as it became clear there was possible mink to human spread.”

Mink-to-human transmission has also been reported in Denmark, the Netherlands and elsewhere.

Overall, transmission of the virus from animals to humans is believed to be rare. Humans are far more likely to spread the virus to one another, or to other species, than they are to catch it from animals, experts say.