As monkeypox subsides, experts grapple with the possibility of long-term consequences

Since the world began confronting a global outbreak of monkeypox in the spring, the scientific community has had plenty of reasons to rue the fact that for decades this virus has been understudied.

Here’s another one: Because of that oversight, doctors treating people who have been infected with monkeypox can’t answer with certainty whether some of them will face any long-term health consequences, referred to as sequelae in the field of medicine. (The word comes from Latin and means “that which follows.”)

“If we had had a strong research agenda around monkeypox when it was in Congo and Nigeria, we would almost certainly have some estimate of both the localized skin and the generalized sequelae from the virus,” said Joseph Osmundson, a molecular microbiologist and clinical assistant professor at New York University’s department of biology.

Health professionals treating men — the cases in this outbreak have been overwhelmingly men who have sex with other men — struggle to answer when asked about the risk of lingering effects of the infection. With cases characterized by genital rashes, a number of clinicians believe some of the men who’ve had multiple lesions on and in their penis could face future problems stemming from strictures — narrowing — in the urethra that could affect urination. There may also be, in some cases, permanent changes to the appearance of some men’s penises.

Even men who didn’t have severe infections or need to be catheterized in order to urinate during the acute phase of their illness could face problems down the road, suggested Walter Falconer, a urological surgeon in private practice in Atlanta who has treated a couple of monkeypox patients.

“It’s quite possible that we’re going to see some late manifestations in the urologic arena of some of these men,” Falconer said.

If you do a search for “monkeypox” and “sequelae” in PubMed, the database of biomedical and life sciences publications maintained by the National Library of Medicine, you’ll draw up 79 references. Half of them were published in 2022, meaning they cannot contain new information on long-term consequences of infections; the period of follow-up of cases from the global outbreak is still too short. Many of the pre-2022 publications relate to research in animals and studies of vaccines and drugs. Few detail the aftermath of monkeypox infection among people.

A case series of 282 monkeypox cases in the Democratic Republic of the Congo that was published in 1987 in the Journal of Infectious Diseases suggested serious side effects were rare; they were seen in only 8% of patients who hadn’t been vaccinated against smallpox. Given that smallpox vaccination ended decades ago, and most of the men infected are under the age of 50, the majority of the contemporary monkeypox patients would fall into the unvaccinated category.

“The commonest sequelae were the pitted scars that developed on the face of most unvaccinated … persons,” the authors wrote. “However … the scars were superficial and were likely to disappear, but about half of the scars from lesions seen initially on the face and body were detectable two to four years after illness.”

It’s difficult, however, to draw conclusions about the current outbreak based on the study. Around 1987, monkeypox was a disease of children in affected countries in Africa; more than 90% of the 282 cases described in the study were under the age of 15. And despite the observation that scars could be seen for years after illness, it appears that most of the data were gathered over a period of weeks or a few months after the infections occurred.

One possible long-term consequence that the study does reference is blindness. Four children in the group developed blindness in one or both eyes and a number of others developed impaired vision after lesions formed on their corneas. It is a risk that worries John Brooks, a medical epidemiologist in the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the Centers for Disease Control and Prevention.

On Monday, the CDC published a report on five cases of monkeypox in the United States where infection in one or both eyes occurred. One man suffered significant vision loss; it is currently unclear if the damage is permanent.

Brooks said that in some cases of vision damage from ocular monkeypox, a corneal transplant will restore the vision loss. “But you don’t want to have that problem,” he said, noting that people who have monkeypox should practice good hand hygiene and refrain from touching their eyes.

A number of physicians who have treated men with monkeypox infections say that while the illness is extremely painful, most people seem to recover well.

“So far we have not seen patients with long-term physical complications,” said Jason Zucker, an infectious diseases specialist at Columbia University Irving Medical Center and assistant medical director of the New York City S.T.D. Prevention Training Center at Columbia University.

“Our penile ulcers have resolved,” he said. “I don’t want to dismiss the scarring and the sort of mental aspect of that on patients. [But] functionally, so far, none of my patients have told me that they’re having functional issues, which is really great.”

Some of the more complex cases involve secondary bacterial infections, where the tissue damage is aggravated when lesions become infected.

“There has been wound healing that needed to be managed because some of these lesions get infected and can get pretty deep,” Zucker said. “But for the most part, usually by the end of two or three weeks most of these things have fully resolved.”

Likewise, Anu Hazra, an infectious diseases physician at Chicago’s Howard Brown Health, said most of the patients he has treated have made a good recovery.

“Persisting rectal pain or urethral pain is not something that we’ve commonly seen, thankfully,” said Hazra, who is also an assistant professor of medicine at the University of Chicago in the section of infectious diseases and global health.

The most common consequence of infection Hazra has seen is scarring, noting that in people with darker skin, there’s temporary pigment loss. It comes back, he said, “but it can take weeks for that to happen.”

Some men who were uncircumcised when they contracted monkeypox may need to have their foreskin removed as a consequence of the scarring, Brooks said.

“We’ve got guys who’ve had their foreskin very, very involved, covered in these pox lesions,” he said. “And in some cases, if a man is left with enough scarring, that foreskin can become tight enough that they may need to have their foreskin removed.”

For men who have had a lot of penile lesions, their penises may look different for some time or perhaps permanently, some experts suggested.

Osmundson, who is also a gay health activist, said there is a lot of stigma associated with the scarring caused by monkeypox.

“The majority of my friends who have had monkeypox have not yet felt able to return to a full sex and dating life just because they’re still traumatized or they’re scared of disclosing having had the virus or they’re scared of lesion scars being visible,” he said.

Osmundson worries about whether there could be a post-monkeypox type syndrome detected in some people who contract the infection, noting that a number of viral illnesses are thought to trigger — in rare cases — a condition called myalgic encephalomyelitis or chronic fatigue syndrome, known by the shorthand ME/CFS.

“Any viral infection can have systemic sequelae, a sort of an ME-type disease where you either don’t fully recover from the virus or have symptoms that persist beyond the virus, that are likely — possibly — due to the immune system changes from infection,” he said. “It can happen with influenza, it can happen with a cytomegalovirus, it can happen with Covid, etc., etc. So could it happen with the poxviruses? Absolutely.”

Brooks said the CDC will be looking for evidence of whether there is a monkeypox equivalent of long Covid, the persistent symptoms, fatigue and brain fog that a percentage of people who have had Covid-19 suffer from after they recover from their initial infection. He noted, though, that the two infections are very dissimilar.

Boghuma Titanji, an assistant professor of infectious diseases at Emory University who has treated a number of men with monkeypox, is concerned about long-term damage to the urethra, the vessel through which urine and semen pass.

Titanji has seen patients who have been unable to urinate, because of lesions on and in the penis. In some of those cases, inserting a catheter has allowed the men to pass urine while allowing the surface of the urethra to heal. But in some cases, more aggressive treatment has been required.

“If they present [for care] too late, and they have too much swelling that you cannot even pass a catheter — which I have seen — then the urologist has to make an artificial opening through the abdomen directly into the bladder,” she said, suggesting some of these men will need to undergo procedures to restore the urethra.

“And for most of them they will have some residual dysfunction that they would just have to live with for the long term. Issues with urination and voiding,” she said. Those could include more frequent urinary tract infections and bladder pain.

One of the patients Falconer treated needed a suprapubic catheter, a tube that was inserted into the bladder via an incision above the groin. He agreed with Titanji that some of the people who have experienced severe manifestations of monkeypox could indeed suffer from more frequent UTIs and may even develop “overflow incontinence” — where a small amount of urine is involuntarily released when they cough or sneeze.

Charting the long-term consequences of monkeypox infection will take time, but it is a critical task, Brooks said.

“If there were long-term consequences of this monkeypox infection, we’d want to know that both because it’s important to be prepared so the medical system can be ready and to anticipate a certain number of people will have a problem,” he said. “But if it’s important enough that it could have really serious consequences, that would become an important part of our prevention messaging.”