First U.S. Monkeypox Death Confirmed in Los Angeles—Here's How the Disease Can Be Fatal

The death of a Los Angeles county resident marks the first confirmed monkeypox fatality in the U.S., L.A. public health officials said in a statement Monday. A death in the Houston area in late August may have also been a result of monkeypox, though Texas public health officials have not yet confirmed the cause in that case.

Death from monkeypox is quite rare—now several months into the outbreak, nearly 22,000 people in the U.S. have tested positive for the disease. However, just 19 people globally have died from monkeypox, while more than 59,000 have been infected.

But even though monkeypox isn't frequently lethal, the virus can, in some cases, cause severe complications or death.

Here's a look at who's most at risk for dying from monkeypox, how TPOXX treatments can help save lives, and whether there may be more life-threatening monkeypox cases in the U.S. and around the world.

With a Weakened Immune System, Monkeypox Can Be Deadly

As is the case with many other infections, people who are immunocompromised are at the greatest risk of having a severe or life-threatening case of monkeypox.

"Ideally, if you get monkeypox, the virus goes into your lymph system, and then your immune system contains it there," Jill Foster, MD, division director of pediatric infectious diseases at the University of Minnesota Medical School, told Health. "But if your immune system can't handle it, then what happens is that it then spreads and can spread to your organs—your liver or your spleen—and can cause a whole systemic reaction."

Typically, however, monkeypox is a self-limiting disease, which means people can usually fight off the virus on their own. Historically, there have been very few life-threatening cases associated with monkeypox Clade 2—which is responsible for the current global outbreak—as opposed to the Clade 1 virus, which can be more severe.

"The Clade 1 is when it's more common to see the more serious, severe manifestations," Dana Mazo, MD, clinical associate professor of infectious disease at NYU Langone Health, told Health. "But we had always been concerned that immunocompromised patients could—even with this less dangerous form—could develop these more severe complications."

The L.A. monkeypox patient who died was "severely immunocompromised," though public health officials did not release any further details about their health history.

When those who are immunocompromised come into contact with monkeypox, it's a concerning situation. Some patients, Dr. Mazo said, are taking immunosuppressant medications for an organ transplant, and can stop taking those medications when exposed to monkeypox. But for other people—those with cancer, people with immunodeficiency disorders, or those with human immunodeficiency virus (HIV)—they may be more vulnerable.

This last group—HIV patients—could be especially at risk. Men who have sex with men make up by far the largest group of monkeypox infections, but gay and bisexual men are also the group most affected by HIV, which suppresses the immune system. Some surveillance data in the U.S., European Union, and England have found that, for men who have sex with men that are infected with monkeypox, between 28% and 51% of them also have HIV infections.

"Monkeypox and HIV are both viruses, and they both attack the same part of the immune system," Dr. Foster said. " If you already have a problem with your T cells, or you already have a problem with how your immune system regulates itself, what's going to happen is either your immune system problem is going to get worse if you have advanced HIV already, it's going to kind of put you over the edge. And even if you don't have advanced HIV, the infection for the monkeypox is going to simulate advanced HIV."

People with HIV who become infected with monkeypox may be infectious for longer, and can experience more severe disease because their immune systems can't get rid of the virus as efficiently. In such cases, the Centers for Disease Control and Prevention (CDC) recommends individuals receive vaccines, medical treatment, and close monitoring if they're exposed to monkeypox.

Severe, Life-Threatening Complications from Monkeypox

Not only are monkeypox infections in immunosuppressed people longer and more severe, but if the disease is given time to progress, it can cause life-threatening complications.

"If it's someone who has a really high level of virus in their blood and really high level of infection, that can lead to this encephalitis involving the areas around the brain and around the spinal cord," Dr. Mazo explained.

Encephalitis is severe swelling of the brain that, in these cases, may be from the monkeypox virus itself invading the nervous system, or a complication of the body's immune response to it. Two reported cases of encephalitis were reported in men infected with monkeypox this summer, the CDC said on Wednesday, though both recovered.

Another concern is that monkeypox can cause sepsis—which involves dangerously low blood pressure and high fevers—Dr. Mazo said. Pneumonia can also kill people with severe cases of monkeypox, Dr. Mazo added. It's not clear if the L.A. resident who died had any of these three conditions.

Such complications are not always life-threatening, but even without a risk of death, in these situations the disease can be quite severe. The typical lesions associated with the disease can be tough to deal with, and may cause a severe infection, too.

"If you think about other dangerous, severe infections, sort of what you get concerned about first off is pain," Dr. Mazo said. "It's very, very painful lesions. I've had so many patients describe it as broken glass, knives cutting. The infections can be in your throat, in your rectum, in your urethra."

These internal lesions are incredibly painful, Dr. Foster agreed, as are lesions near or in your eye, which can sometimes cause blindness. Where these lesions show up or the complications you get from the virus isn't always predictable—even people who are not immunocompromised can have severe cases.

TPOXX Can Improve Immune System Response

The good news is that there's already a treatment available to help some monkeypox patients. Tecovirimat, or TPOXX, is a smallpox antiviral, but it's being used to prevent death and severe illness for patients whose immune systems may need help getting over monkeypox.

"The virus goes through a whole lifecycle of various stages—binding with the cell, and then building itself up in the cell, and then being released from the cell. And [TPOXX] just goes in and shuts it down," Dr. Foster said. "That's what the immune system would do too, ideally. But it goes in and helps so that the immune system doesn't have as high a virus to try to fight."

The drug isn't always perfect, however. It has to be administered earlier on in the infection to prevent life-threatening outcomes.

"With most stuff that we use for viruses the earlier you get it in, the better, because then it really shuts the virus down," Dr. Foster added. "Once the virus has spread through the whole body, and has actually started causing organ damage, it's hard to reverse."

Staying Safe

Even though the U.S. now has a confirmed monkeypox fatality case, Drs. Mazo and Foster say that deaths from the virus will likely, for the time being, continue to be rare.

"There can always be a mutation, there can always be a change, but [monkeypox] doesn't mutate all that quickly. This clade has been around in Nigeria since at least 2017, so it seems unlikely to become more dangerous," Dr. Mazo said.

The fact that monkeypox is slow to mutate is also a good thing for treatment methods, Dr. Foster explained. There is of course the possibility that monkeypox could evolve to become resistant to TPOXX. But given the virus' history of slow mutation, it's less likely that that will happen soon.

But with monkeypox being, in rare cases, fatal and in many cases severely painful, it's important to continue to slow the spread. This includes adopting safer sex practices, isolating if you come into contact with the virus, and getting vaccinated if you can.

Experts are also concerned that monkeypox could spread into new communities or groups, potentially creating new cases where the virus could be deadly.

"It's spreading into our communities of color," Dr. Foster said. "It's likely that it's going to strike more people that already have underlying problems, especially HIV."

An increased number of children contracting monkeypox is also a concern, Dr. Foster added. Though there isn't much data available about Clade 2 infections in children, the CDC said that in Clade 1 infections, the disease is much more severe in kids under the age of 8.

Though monkeypox deaths are rare, hopefully information about such outcomes will encourage people to, at the very least, be on the lookout for the disease, Dr. Mazo said. If more is known about how dangerous monkeypox is and how it spreads, then there may be a better chance of preventing situations where immunocompromised people could become seriously ill.

"This stuff does not change the concern level," Dr. Mazo said. "Right now, monkeypox is still primarily in a few social networks. Definitely, there are some cases outside of those social networks, so people should be aware if they develop a new rash or develop symptoms—especially if they're immune compromised—to make sure to tell their physicians so that they can be tested."