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(CNN) -- Six people who tested positive for monkeypox -- two in New York City, two in Chicago, one in Nevada and one in Maryland -- have died, local health departments have confirmed.
The New York City Department of Health and Mental Hygiene said it was "deeply saddened by the two reported deaths, and our hearts go out to the individuals' loved ones and community."
"Every effort will be made to prevent additional suffering from this virus through continued community engagement, information-sharing, and vaccination," the NYC DOH said.
The two Chicagoans who died after testing positive for monkeypox had multiple other health conditions, including weakened immune systems, according to the Chicago Department of Health (CDPH).
"Though the number of new MPV cases has declined substantially since summer, this is a stark reminder that MPV is dangerous and can cause serious illness, and in very rare cases, even death," said CDPH Commissioner Dr. Allison Arwady.
Monkeypox was a contributing factor in the death of a Maryland resident, who was immunocompromised and experiencing a severe case, the Maryland Department of Health (MDH) said.
"If you are eligible, such as being immunocompromised or at-risk, the best way to protect yourself against serious illness from MPX is by getting vaccinated," said MDH Deputy Secretary for Public Health Services Dr. Jinlene Chan.
The first confirmed US death due to monkeypox was reported in Los Angeles County in September. A person with monkeypox in Houston died in August, but officials have not determined whether the virus caused the death.
In late September, Ohio reported its first death of a person with monkeypox but noted that "the individual also had other health conditions."
It can be difficult to determine if someone has died of monkeypox. Not only would the virus have to be detected in their body, but forensic pathologists would have to "connect the dots" as to how the infection caused the death, such as by affecting certain organs, according to Dr. Priya Banerjee, a board-certified forensic pathologist in Rhode Island and clinical assistant professor of pathology and laboratory medicine at Brown University.
"To die from any infection, it's usually systemic -- meaning the whole body is affected -- or a significant organ is affected, like the heart, lungs, liver or brain," she said. "It's not that they die with the infection; it's because of it. So that's the differentiation you have to make, and that's a pretty significant differentiation. I think limitations come in with not just identifying if or what organ is affected but to what extent -- and no one is going to call it a cause of death unless that's confirmed."
New monkeypox cases in the United States have been steadily dropping in recent weeks but concern remains about the possibility of severe illness or death, especially in immunocompromised people.
There were 27,884 probable or confirmed monkeypox cases reported in the US as of Friday, according to the Centers for Disease Control and Prevention.
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