How satirical is it that as soon as COVID-19 fades to an endemic level, outbreaks of two rare viruses make themselves known—one related to a virus the United States wiped out in 1972 thanks to the success of vaccination.
While monkeypox and adenovirus are not as concerning or life-threatening as COVID-19, they can both be fatal, with the latter already infecting at least 180 children, killing 6 of them. Monkeypox is only fatal in 1 to 11% of those infected, and while several travelers a year typically arrive in the U.S. and Europe with the virus, such a large chain of person-to-person transmission throughout 16 countries across the globe has never been seen before. This prompted the Centers for Disease Control and Prevention (CDC) to issue a Level 2 travel health notice last week, and the World Health Organisation (WHO) to issue a disease outbreak notice.
Like COVID-19, monkeypox is a zoonotic disease that is believed to have originated in rodents, but is seen in other animals throughout Africa, including squirrels, dormice and different species of monkeys. Animal-to-human transmission occurs through direct contact with the blood, bodily fluids, or lesions of infected animals, with the consumption of food products of infected animals also a possible risk factor. Human-to-human transmission can result from close contact with respiratory droplets—although it is not considered a respiratory virus—skin lesions or recently contaminated objects. It is unclear at this time if monkeypox is sexually transmittable. The incubation period for monkeypox is typically 6 to 13 days but can be anywhere from 5 to 21 days.
As of Wednesday, the CDC has confirmed nine monkeypox cases in seven states— Massachusetts, Florida, Utah, Washington, California, Virginia and New York. Other recently confirmed cases are in Europe and Australia, where monkeypox is not endemic.
Clinical care for monkeypox is mostly limited to alleviating symptoms and managing complications. An antiviral agent known as tecovirimat that was developed for smallpox was licensed by the European Medicines Agency (EMA) for monkeypox earlier this year based on data in animal and human studies, but it is not yet widely available. It is not approved for use on monkeypox in the U.S.
However, the U.S. does have options when it comes to vaccines. First and foremost, vaccination against smallpox is about 85% effective in preventing monkeypox. The U.S. didn’t stop routinely vaccinating against smallpox until 1972, meaning a good percentage of people alive today already possess the necessary antibodies.
Additionally, there are currently two FDA-approved vaccines for monkeypox. The Jynneos vaccine by Bavarian Nordic was approved in 2019 for adults at high risk of smallpox and monkeypox infection. CDC officials said earlier this week there are more than 1,000 doses of Jynneos in the national stockpile, and they expect that number to increase quickly in the coming weeks. U.S. health officials are currently in the process of releasing some Jynneos vaccines.
The U.S. also has more than 100 million doses of an older smallpox vaccine called ACAM2000, originally produced by Sanofi, now by Emergent BioSolutions. Laboratory personnel who directly handle cultures of animals infected with smallpox and other orthopoxviruses, including monkeypox, cowpox, and variola, routinely receive this vaccine. However, it does have side effects, particularly in those who are immunocompromised.
Unlike SARS-CoV-2, monkeypox is unlikely to spread asymptomatically as the characteristic skin lesions it causes typically do not go unnoticed by the infected. While monkeypox can be spread by very close contact with respiratory droplets, it is not a traditional respiratory disease. The transmission route is more likely through skin lesions, making asymptomatic spread uncommon. Another critical difference between SARS-CoV-2 and monkeypox is that the latter is not a rapidly mutating virus.
Monkeypox isn’t the only virus the CDC has been concerned about lately. Officials are looking into 180 possible cases of adenovirus causing severe liver damage in children. Of these, 15 children required liver transplants and 6 died.
Following a wave of cases in Europe, doctors in the United States first noticed clusters of pediatric hepatitis (inflammation of the liver) in Alabama in October 2021. Since then, over 20 other countries have reported hundreds more cases, though the largest numbers remain in the UK (197 cases) and the U.S. (180 cases).
Health officials are stumped by this mysterious illness. Adenovirus 41 has been detected in the blood of almost all of the stricken children, but oddly not found in their diseased livers. Even so, adenovirus 41 is an extremely common stomach bug marked by minor diarrhea, nausea and vomiting.
In fact, adenovirus infections are so common that they are not systematically tracked in the U.S.
"If we start testing everybody for the adenovirus, they will find so many kids that have it,” Heli Bhatt, M.D., a pediatric gastroenterologist who treated two Minnesota children with the liver problems recently told the Associated Press.
So, what is causing a normally minor illness to be fatal? Recent genetic analysis by the CDC has turned up no evidence that a new mutation of the virus is to blame.
In April, North Carolina health officials downplayed a possible link between the mystery disease and COVID-19 since two pediatric patients were thought to have never been infected by SARS-CoV-2. And indeed only 10 to 15% of children with the mysterious hepatitis had COVID-19, according to hospital-given nasal swab tests.
But, scientists are still drawing a link between the two, especially given that unusual liver function post-COVID-19 infection has been documented in both children and adults. In 2020, Rohani et. al concluded that “liver and pancreatic enzymes may be elevated during pediatric COVID-19.”
Similarly, in May 2021, Italian researchers wrote about a possible hepatitis link to COVID-19 after treating a previously healthy 10-year-old boy with acute hepatitis who subsequently tested positive for SARS-CoV-2. In September 2021, Brazilian researchers reported on the case of an immune-compromised 5-year-old with COVID-19-induced hepatitis. Researchers in Ohio reported nearly the same the following month—COVID-19-incuded acute liver failure due to hepatitis in a 3-year-old.
And now, multiple studies have been published this month alone linking hepatitis and SARS-CoV-2 specifically in the pediatric population. For example, researchers in India have documented what they call “CAH-C,” or COVID-19-associated hepatitis in children, a unique presentation subsequent to asymptomatic infection of SARS-CoV-2.
“With the emergence of newer variants of concern, including the Delta variant which predominated the second wave of infections in India and has now spread to more than 142 countries with changing presentations, CAH-C might be one of them,” the authors write in medRxiv.
Also published in medRxiv this month, scientists at Case Western University tested whether there was increased risk of elevated serum liver enzymes and bilirubin following COVID-19 infection in children. They performed a retrospective cohort study on a nationwide database of patient electronic health records in the U.S, comprising 796,369 children between the ages of 1 and 10—including 245,675 who contracted COVID-19 in the past two years and 550,694 who contracted non-COVID respiratory infections during the same timeframe. Data analysis showed children previously infected with SARS-CoV-2 were at a significantly increased risk of elevated serum liver enzymes and total bilirubin when compared with children infected with other respiratory infections. This elevated risk continued for 1, 3 and 6 months following COVID-19 infection.
“These results suggest acute and long-term hepatic sequelae of COVID-19 in pediatric patients,” the researchers write. “Further investigation is needed to clarify if post-COVID-19 related hepatic injury described in this study is related to the current increase in pediatric hepatitis cases of unknown origin.”
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