As the number of global monkeypox cases rises above 1,300, we’re getting a clearer picture of how the infection is playing out for individuals. For the most part, it’s been pretty manageable: Affected people get clusters of small, painful bumps or blisters — often in the genital area after sexual contact — which are accompanied by fever and lymph node swelling. Often, the rash spreads to the arms, legs, and face.

While monkeypox is known to leave behind scarring that can cause cosmetic problems, the less virulent West African version of the virus that is currently circulating is rarely lethal. As of June 2, none of the people involved in the current outbreak have died, in countries where the disease is not endemic.

What’s more, it’s relatively easy to avoid an infection. The virus is generally spread through contact with a monkeypox sore, so not touching others’ rashes is a solid prevention strategy.

With monkeypox infections preventable and not particularly deadly, it might be easy to brush off the threat of this pathogen. But we shouldn’t, and for an important reason: These infections can kill.

As Covid-19 made clear, one person’s mild infection can be another person’s death sentence. A minority of people are more at risk due to pre-existing conditions — and as the outbreak grows, so does the likelihood that monkeypox will find more vulnerable individuals. That makes it a pathogen worth containing — and worth having and sharing good treatments for. It also makes it worth figuring out who is most likely to get hurt the most, as the outbreak continues to spread.

The risk of monkeypox complications is higher for people who are immunocompromised, pregnant, or have certain skin conditions

Our best understanding of the range of problems monkeypox can cause comes from Nigeria, where health care providers have identified more than 550 cases of monkeypox since an outbreak erupted there in 2017.

The skin rash most people get due to monkeypox infection can be exquisitely painful, in some cases requiring hospitalization just to control the discomfort the bumps and blisters can cause. But what makes monkeypox dangerous is when the virus disseminates to organ systems beyond the skin, said Andrea McCollum, an epidemiologist at the Center for Disease Control’s poxvirus and rabies branch.

In the cases where monkeypox infection led to death, patients suffered from severe infections of the brain, the bloodstream, or the lungs. These complications may have resulted from direct viral effects on organs or from bacterial infections that the virus’ inflammatory effects helped facilitate, often called “secondary” infections.

These complications are most likely among people with severe immunosuppression, according to Dimie Ogoina, an infectious diseases physician at Niger Delta University in Bayelsa, Nigeria, and lead author of a report describing outcomes among Nigerian patients hospitalized between 2017 and 2018.

Since that outbreak in Nigeria began, nine people have died of monkeypox infections, he explained in an email. Four of the people who died were living with uncontrolled HIV infection, Ogoina said, while one was a newborn and another had underlying kidney disease and was taking immunosuppressive medications. Additionally, one pregnant woman with monkeypox had a spontaneous miscarriage of her pregnancy at 26 weeks of gestation.

It’s not entirely clear why certain immunocompromised states put people at increased risk for monkeypox complications, said Stuart Isaacs, a virologist at the University of Pennsylvania who studies poxviruses, the family that includes monkeypox virus.

Researchers have tried to clarify the exact types of immunocompromised states that raise poxvirus risks using animal models. Those experiments have shown that CD4 T cells (which are depleted by untreated HIV infections) and antibody-producing B cells play a leading role in controlling the initial infection. However, there’s currently little human data to go on, said Brett Petersen, an internist and medical epidemiologist at the CDC.

For now, the agency’s treatment recommendations currently suggest that people with a broad range of immunocompromising conditions are at risk for severe disease (including HIV, a variety of cancers, organ transplants, certain stem cell transplants, and certain autoimmune diseases), as are children below the age of eight.

Also at higher risk are people with pre-existing skin conditions like eczema (i.e. atopic dermatitis), said McCollum, possibly because people spread infection from one body site to another when scratching, and pregnant people, who have a higher likelihood of spreading the virus to their pregnancies and potentially causing miscarriage.

Risk factors for monkeypox infection overlap with risk factors for a key immunocompromised state: Uncontrolled HIV

In the current global outbreak, monkeypox seems to be spreading largely through the kind of close contact that happens during sex. The same kinds of contact that put people at risk for monkeypox also puts them at risk for uncontrolled HIV infections. And so that raises the concern that people with uncontrolled HIV are at highest risk, not only for getting infected with monkeypox but also for suffering its worst consequences.

“This is the thing that worries me the most,” said Gregg Gonsalves, an epidemiologist at Yale University’s School of Public Health and an HIV and global health activist. On average, 13 percent of Americans with HIV are unaware of their diagnosis and not on treatment, but that proportion is as high as 20 percent in some Southern states and higher still in several of the Plains and Western states. ”If there’s a fifth of the HIV-positive community that doesn’t know their status, it means they’re at risk,” said Gonsalves.

A disease spread during sex can be contained if people avoid sexual contact when they’re sick, or rigorously use precautions like condoms or dental dams. And while many sexually active people do use these precautions, people whose sexual activity is stigmatized — like closeted gay or bisexual men — are less likely to do so. For these groups, homophobia and other stigmas often interfere with getting tested and seeking care for sexually transmitted infections, including HIV.

That means the same marginalized people who are at higher risk for untreated HIV are at higher risk for monkeypox infections — and for severe consequences of both. In many parts of the US, homophobia disproportionately prevents Black men from getting lifesaving HIV treatment — a major contributor to higher rates of HIV infections and deaths among Black Americans.

The more the outbreak spreads, the more likely that, eventually, it will reach higher numbers of immunocompromised people, where it could lead to terrible consequences. That should move us to urgent action regardless of where the spread is taking place, Ogoina said.

“If global action is not taken to better understand the virus and disease everywhere and to develop innovative countermeasures to address the challenge of monkeypox everywhere,” wrote Ogoina, there’s a serious risk. Then we could see big changes in who the virus infects and how much havoc it wreaks.