On April 15, the World Health Organization (WHO) issued a notification that as of April 8, 74 cases of “acute and severe childhood hepatitis of unknown origin” had been detected in the UK ( Hereinafter referred to as “hepatitis of unknown cause in children”) [1].
On April 23, the WHO issued another notification: As of April 21, 11 European countries and the United States had reported at least 169 cases of unexplained hepatitis in children, and most of the cases (114) appeared in England. One child has died, and 17 children (about 10%) require liver transplantation [2].
(As of April 23, 2022, distribution of cases of hepatitis of unknown cause by country. Image source: WHO)
“Hepatitis of unknown origin in children” is easy to conjure up. In early 2020, the new coronavirus infection was once called “pneumonia of unknown cause”. Is this disease a new infectious disease?
Tencent Medical Code combs the public information of WHO and various countries, and tells you the current known facts about hepatitis of unknown cause-
Scotland, UK was the first region to report the discovery of unexplained hepatitis in children. An investigation report of 13 cases in Scotland showed that one of them can be traced back to January 11 (the date of admission), but the remaining 12 All cases were admitted to hospital in March and April [3].
In previous years, the number of people with unexplained hepatitis in Scotland was usually less than four, leading to a notification in Scotland at the end of March [3].
At this time, it is uncertain how rapidly unexplained hepatitis increases in children [2].
None of the children were tested for a common hepatitis virus (hepatitis A to E) [2]. Who is the culprit?
Is it the coronavirus?
Dr. Jean-Marc Sabatier, research director of the French National Academy of Sciences, said that the acute hepatitis has similar pathophysiological characteristics to the new coronavirus infection.
Some studies have shown that the new coronavirus uses angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells, resulting in the destruction of ACE2 and an imbalance of the renin-angiotensin system (RAS). And our liver cells have the ACE2 receptor on their surface, which is the target of the new coronavirus spike protein and vaccine spike protein [4].
However, this is a theoretical speculation and more research is needed.
Furthermore, only 20 of the 169 children tested positive for SARS-CoV-2, and 19 of them were co-infected with SARS-CoV-2 and adenovirus [2].
Therefore, the link between unexplained hepatitis in children and COVID-19 is currently uncertain.
Is it a Covid-19 vaccine?
There are foreign reports [4] that the new crown vaccine based on the Omicron spike protein has risks, and young children who receive the new crown vaccine may have the same liver inflammation.
For the speculation about the disease caused by the new crown vaccine, the WHO’s notification also responded: The vast majority of children have not been vaccinated against the new crown vaccine[2] .
In addition, the majority of children vaccinated against the domestically produced new crown vaccine in my country have not experienced such cases, so there is no need to worry about the unexplained hepatitis caused by the new crown vaccine in children.
Is it an adenovirus?
The current mainstream view is more inclined to believe that the causative agent of this unknown hepatitis is “adenovirus”, this is because at least 74 of 169 cases have been detected Adenovirus [2]. And, in the United Kingdom, which has the highest number of cases, a significant increase in adenovirus infection has also recently been observed [2].
(A diagram of what an adenovirus looks like under a microscope and its structural pattern. Image source: “Medical Microbiology (8th Edition)”)
Adenovirus can be divided into seven subgroups A~G, 42 serotypes, and can be transmitted by droplet, fecal-oral route or contact. Symptoms vary with adenovirus infection, but respiratory symptoms are more common [5,6]. Hepatitis may also occur in immunocompromised patients, but is commonly associated with adenovirus type 5 [7].
And 18 of the 74 children with adenovirus detected were adenovirus type 41, and patients with adenovirus type 41 had not previously developed symptoms like this unexplained hepatitis [ 2]. Therefore, more research is needed for the determination of pathogens.
Adenovirus deserves attention as a vector for SARS-CoV-2 vaccine. Therefore, there are also some views that this unexplained hepatitis may be related to the vaccination of SARS-CoV-2 with adenovirus vector. However, further analysis found that children with unexplained hepatitis have hardly received any form of new crown vaccine, so it is currently speculated that the correlation is not large.
Combining the above tests, there are still several conjectures about the cause[2]:
During the COVID-19 outbreak, the protective measures for susceptible groups were strengthened, and the transmission route was greatly cut off, resulting in a reduction in the level of adenovirus transmission and a relative reduction in the production of antibodies in children who were rarely exposed to adenovirus. Thus increased susceptibility to adenovirus.
A new type of adenovirus may have emerged.
COVID-19 co-infection with adenovirus.
But further verification is required.
169 cases ranged in age from 1 month to 16 years [2]. Of the 13 cases in Scotland, 12 of the children were five years of age or younger [3]. Common symptoms in these children include[2]:
Gastrointestinal symptoms: abdominal pain, diarrhea, vomiting.
Alanine aminotransferase was significantly elevated: Alanine aminotransferase levels are an important indicator of liver function. The normal range of this enzyme is 10 to 40IU/L, and children can reach 500IU/L, and some children can reach 4000IU/L[3]
Jaundice: Jaundice, which is a yellowing of the skin or sclera (whites of the eyes), is a common manifestation of liver disease and is caused by elevated serum bilirubin concentrations.
The unexplained hepatitis this time has a great ability to damage the liver function of the children. About 10% of the children need liver transplantation, and one person died.
Unfortunately, it is still uncertain whether the disease is contagious. Countries reporting cases are currently screening larger groups and conducting epidemiological investigations.
Based on the WHO report, adenovirus is currently relatively more likely to be the cause of unexplained hepatitis in children [2], so this article will describe adenovirus preventive measures.
Adenovirus infection is actually a relatively common disease. It is mainly prevalent in spring and winter. Infants, the elderly, and those with low immunity belong to susceptible groups. It is easy to occur in kindergartens, universities, barracks and other places. Mass infection [6].
Adenovirus can be transmitted through droplets, fecal-oral route or contact, but there is currently no vaccine against adenovirus in China, it can only be done through good personal hygiene ( Wash your hands frequently, avoid close contact with patients), wear masks, etc. for protection.
In addition, some new crown vaccines use adenovirus vector vaccines, but adenovirus vector vaccines will delete genes related to replication in adenoviruses, making adenoviruses unable to replicate in the body. Therefore, there is no need to worry about adenovirus infection due to vaccination with adenovirus vector.
The above is the current public information on the recent outbreak of unexplained hepatitis in children, and it is still unknown whether this disease will become a new large-scale epidemic. No similar cases have been reported in the country.
Some marketing accounts may over-interpret, creating rumors and panic. But until more research comes out, there’s no need to be overly anxious.
Reviewer: Zhou Ning
Shanghai Tongji Hospital Pediatrician
References
[1]World Health Organization (15 April 2022). Disease Outbreak News; Acute hepatitis of unknown aetiology – the United Kingdom of Great Britain and Northern Ireland. Available at: https:https:/ /www.who.int/emergencies/disease-outbreak-news/item/acute-hepatitis-of-unknown-aetiology—the-united-kingdom-of-great-britain-and-northern-ireland
[2]World Health Organization (23 April 2022). Disease Outbreak News; Multi-Country C Acute, severe hepatitis of unknown origin in children. Available at: https:https://www .who.int/emergencies/disease-outbreak-news/item/multi-country-acute-severe-hepatitis-of-unknown-origin-in-children
[3]Marsh K, Taylor R, Pollock L,et al. Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022[J]. Eurosurveillance, 2022, 27(15): 2200318.
[4] Acute childhood hepatitis : a link with Covid-19[EB/OL]. French Daily News. 2022/2022 -04 -24. https:https://frenchdailynews.com /society/4581-acute-childhood-hepatitis-a-link-with-covid-19.
[5] Li Fan, Xu Zhikai. Medical Microbiology (8th Edition) [M]. People’s Health Publishing House, 2013: 248-249.
[6] Lin Guowei, Wang Jiyao, Ge Junbo. Practical Internal Medicine (15th Edition) [M]. People’s Health Publishing House, 2017: 301.
[7] Phyllis Flomenberg, Tsoline Kojaoghlanian. Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection [EB/OL]. Uptodate. 2022/2022 -04 -24. https: https://www.uptodate.com/contents/en-Hans/pathogenesis-epidemiology-and-clinical-manifestations-of-adenovirus-infection.
Author: Chen Zexiong
Editors: Yu Jia, Zhao Yanan, Ye Zhengxing
Proofreading: Wu Yihe | Typesetting: Li Yongmin
Operation: Han Ningning | Coordinator: Ye Yichu