Clinical Context

The world continues to be concerned regarding further mutations affecting the SARS-CoV-2 virus. The Omicron virus remains the predominant variant worldwide in early fall 2022, and a study by Ou and colleagues evaluated the genetic signature of Omicron. Their results were published in the April 26, 2022 issue of Nature.^[1]

Omicron BA.1 was found to have 18 core mutations of the SARS-CoV-2 spike protein gene sequence, and BA.2 was found to have 27 such mutations; however, only 15 of these mutations were specific to Omicron. The BA.1 variants was more genetically similar to the Alpha variant of SARS-CoV-2 compared with later variants. The changes noted in Omicron variant could assist the virus in resisting the immune system and gaining entry into bronchial epithelial cells compared with previous variants.

The world now waits with apprehension at the possibility of a new pandemic, this time with monkeypox, but a monkeypox pandemic similar to the COVID-19 pandemic seems highly unlikely given the much lower infectivity rates of monkeypox. Nonetheless, the current article by Johnson and colleagues rings the alarm that allowing monkeypox to slowly spread unabated may result in disaster.

Study Synopsis and Perspective

Monkeypox cases are declining in the United States and the United Kingdom, but experts are urging the public to continue efforts to stanch the spread of the virus. Continued transmission of monkeypox provides more opportunities for the virus to the mutate, according to Philip Johnson, PhD, an assistant professor of biology at the University of Maryland, College Park, Maryland, and colleagues.

"Just because a disease like monkeypox appears to be controllable does not mean it will stay controllable," wrote the authors in a correspondence published October 8 in The Lancet.^[2]

When case numbers are lower -- and therefore less of a public health concern -- viral transmission chains can be longer without causing alarm, Johnson explained.

"The more generations of transmission, the more opportunities there are for mutations to occur," he told Medscape Medical News.

Although it is difficult to anticipate how mutations can affect a virus, these changes in genetic code could be advantageous to the virus, making it more transmissible from human to human and therefore much more difficult to control.

This applies to any virus. The large Ebola outbreak from 2013 to 2016 is an example; a retrospective analysis^[3] found that specific amino acid changes in the Ebola virus increased growth in human cells and may have made the virus more infectious. More recently, the Delta and Omicron variants of SARS-CoV-2 each contained mutations that were associated with higher transmissibility. A recent study^[4] by Isidro and colleagues suggested that monkeypox appears to be mutating faster than expected, although it is not clear if these genetic mutations have changed the virus' behavior.

Zoonotic infections, or viruses that originate from nonhuman animals, at first are expected to be less adapted to people, but that can change over time. When a virus continues to jump from animals to humans -- as monkeypox has done since it was first identified in humans in 1970 -- chances are it will gain a mutation that allows it to spread more effectively between people, said Rachel Roper, PhD, a professor of microbiology and immunology at East Carolina University, Greenville, North Carolina. She was not involved with The Lancetarticle.

"We discounted monkeypox; we didn't pay much attention to it because it had not been that big of a problem," she said in an interview with Medscape. "We think this virus has been circulating now since 2017 and we really just realized it in May."

Although monkeypox received global attention this past summer, the outbreak is now receiving less news coverage, and the public's attention may be waning. Furthermore, the US Congress just dropped billions of dollars from a short-term spending bill that would have provided additional COVID-19 and monkeypox funding.^[5]

Although new cases are trending downward, now is not the time to take our foot off the gas, Johnson and colleagues warned.

"The epidemic is far from over, and continued drive toward elimination is essential," the authors wrote.

Because the virus exists in rodent populations in areas of central and west Africa, it is not possible to eradicate monkeypox as we did smallpox; however, "we could, through vaccination, eliminate any significant human to human transmission," Johnson said.

Johnson also urged a more proactive approach to combating emerging infectious diseases in the future.

"We wrote this article to raise awareness about the importance of dedicating resources to controlling these diseases all the way down to ideally elimination in the countries where they develop, and not just waiting until [these diseases] reach wealthier countries," he said.

Roper agreed that a more global perspective is needed in monitoring and controlling zoonotic disease, but resources are limited.

"The problem is there are a whole bunch of virus groups and a whole bunch of viruses jumping into humans all the time," she said. "We can't predict which virus group is going to be the next one with a big hit. I worked on SARS-CoV-1 back in 2003 to 2009, and I would have predicted that a virus from some other group would have jumped into humans next, before COVID hit," she added.

Johnson acknowledged that it is hard to know where to focus public health resources, considering the hundreds of thousands of zoonotic viruses that may exist. He thought the best approach was to target emerging diseases that already appear to have extended transmission chains, "not just things that are hopping from animals to humans and sputtering out and disappearing, but diseases that appear to have any sustained human to human transmission."

Johnson and Roper report no relevant financial relationships.

Clinical Implications

• In a previous study by Ou and colleagues of the genetic signature of Omicron variants of SARS-CoV-2, Omicron BA.1 was found to have 18 core mutations of the spike protein gene sequence, and BA.2 was found to have 27 such mutations; however, only 15 of these mutations were specific to Omicron. The BA.1 variants was more genetically similar to the Alpha variant of SARS-CoV-2 compared with later variants.
• Models demonstrate that zoonotic viruses with a reproductive number less than 1 are more likely to mutate and become more transmissible among humans. The authors of the current study, Johnson and colleagues, suggest that ring vaccination could reduce the impact of the current outbreak of monkeypox.

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