Deaths from monkeypox in the US are rare, so they can be difficult to confirm

CDC: People with STDs could be more affected by monkeypox 0:53

(CNN) --

More than 25,000 cases of monkeypox have occurred in the United States during the current outbreak, and deaths among monkeypox patients are rare.

Among the few reported deaths, it has sometimes been difficult to determine the role that monkeypox played in the deaths.

"It's similar to what happened to us with Covid: Did you die from Covid, or did you die from Covid? And this is the same scenario: Did you die from monkeypox or did you die from monkeypox?" said Lori Tremmel Freeman, director executive officer of the National Association of County and City Health Officials.

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The first confirmed death in the US from monkeypox was reported in Los Angeles County in September.

A person with monkeypox in Houston died in August, but authorities have not determined whether the virus caused the death.

On Thursday, Ohio reported the first death of a person with monkeypox, but noted "the individual also had other health conditions."

Many of the people infected with monkeypox in this outbreak also have compromised immune systems or underlying health conditions, such as HIV.

This can make it difficult for officials to determine if a death was caused by monkeypox or if the person died of an underlying health condition while infected with monkeypox.

Research in other outbreaks has revealed that deaths from monkeypox most often affect infants, pregnant women, and people with weakened immune systems.

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Experts must ask themselves, "Were his underlying conditions so serious that this type of illness would have a tremendously greater impact on his ability to survive?"

Freeman said.

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Serious disease potential

According to the World Health Organization, there have been more than 68,000 cases of monkeypox and 25 confirmed deaths in the current outbreak.

New cases of monkeypox in the United States have declined steadily in recent weeks, but serious illness or death remains a concern, especially in immunocompromised people.

In an alert sent to health care providers last Thursday, the CDC said some people with monkeypox have had "severe manifestations" of the disease, prolonged hospitalizations or "substantial" health problems.

"Persons who are immunocompromised due to HIV or other conditions are at higher risk for severe manifestations of monkeypox than are immunocompetent persons," the CDC reported.

The Los Angeles County resident who died was "severely immunocompromised and had been hospitalized," according to a news release from the county's Department of Public Health.

"I think this points to the overall message that although we have classified this disease as a mild illness that can be overcome with vaccinations and treatment and other mitigation efforts, for people who already have these conditions, it can be deadly," Freeman said.

"So it's not a disease that you shouldn't worry about, especially if you know you have a compromised immune system or are dealing with some other serious conditions," he added.

"These few deaths, whether or not they were entirely attributable to monkeypox -- meaning people died with monkeypox -- probably wouldn't have happened if they didn't have some of these underlying conditions or if their bodies weren't already compromised."

To die from or with monkeypox

In August, authorities reported that a monkeypox patient in Harris County, Texas, had died, but the role of the virus in that death has yet to be confirmed.

"The medical certifier (usually the attending physician) determines the cause of death and any contributing factors that are recorded on the death certificate. In the case of the Harris County death, they decided to perform an autopsy to gather more information before determine cause of death," Lara Anton, a spokeswoman for the Texas Department of State Health Services, wrote in an email to CNN.

In either case, forensic pathologists often begin the examination by gathering details about the person's medical history and how death occurred.

They may then perform an external and internal examination of the body and collect tissue samples for analysis under a microscope.

This type of postmortem examination is known as an autopsy.

"You learn a lot about infections at autopsy, but at the same time it's an evolving process. It's not easy to make a diagnosis and come to a conclusion," said Dr. Priya Banerjee, a Rhode Island-certified forensic pathologist and associate professor pathology and laboratory medicine at Brown University.

To determine that someone died of monkeypox, not only would the virus have to be detected in their body, but forensic pathologists would have to "connect the dots" on how the infection caused death, for example by affecting certain organs. Banerjee said.

"To die from any infection, it's usually systemic, that is, the whole body is affected or an important organ is affected, such as the heart, lungs, liver or brain," he said.

"It's not that they die with the infection; it's because of it. So that's the differentiation to make, and it's a pretty significant differentiation. I think the limitations go beyond identifying whether the organ is affected or not, but to what extent, and no one is going to claim it's the cause of death unless it's confirmed."

Determining whether someone died of an infectious disease or with an infectious disease isn't always "black and white," said Dr. Mario Mosunjac, a professor of pathology at Emory University School of Medicine and director of autopsy services at the Department of Pathology and Laboratory Medicine, in an email to CNN.

"It is important to realize that the presence of a specific pathogen does not necessarily mean that the pathogen caused death in that patient, but further investigation is usually required," Mosunjac wrote.

"Each clinical case is different, with many conditions that can overlap and interfere with determining the exact cause of death in each individual patient," he said.

"The best answer usually comes in each case after careful consideration of all the factors involved from the point of view of clinicopathological correlations."

How monkeypox can turn deadly

Typically, to determine whether monkeypox has caused or contributed to a death, forensic pathologists look for clues as to how symptoms specifically may have become life-threatening.

"For example, in the case of monkeypox, people often think it's skin lesions and maybe a general malaise and flu-like symptoms. How could it cause death? Well, there are some very rare ways said Dr. James Gill, chairman of the American College of Pathologists Committee on Forensic Pathology.

"If the infection gets to the brain, it can cause encephalitis, which is an inflammation of the brain, and that's very rare," said Gill, who is also Connecticut's chief medical examiner.

"The most common way that many viral infections end up causing death is through a secondary effect, a secondary co-infection. For example, a person can develop pneumonia or a skin infection from these skin lesions, which leads to a bacterial infection that can get into the blood and cause sepsis," he said.

If a person with monkeypox developed pneumonia or a blood infection and died from it, monkeypox would still be considered the cause of death, Gill said, since monkeypox started the chain of events.

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"If they also have lymphoma or AIDS, that would probably be considered a contributing condition because it makes them more likely to die from monkeypox than a healthy person," Gill said.

In most cases, that person would have been hospitalized, he said, and "most of those deaths would be certified by hospital doctors."

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