On 15 April, the World Health Organization (WHO) issued a notification that as of 8 April, 74 cases of "acute and severe childhood unexplained hepatitis" ("unexplained hepatitis in children") had been detected in the UK [1].
On 23 April, the WHO issued another notification: As of 21 April, at least 169 cases of unexplained hepatitis in children had been reported in 11 European countries and the United States, with the majority of cases (114 people) occurring in the UK. One child has died and 17 children (about 10%) need liver transplantation [2].
(As of 23 April 2022, cases of unexplained hepatitis were distributed across countries.) Image source: WHO)
"Unexplained hepatitis in children" is easily associative. At the beginning of 2020, the new crown virus infection was called "pneumonia of unknown cause". Is this disease a new infectious disease?
Tencent Medical Code has sorted out the public information of the WHO and various countries, and told you the current known facts about hepatitis of unknown cause ——
In Scotland, the first region in the United Kingdom to report the detection of unexplained hepatitis in children, the 13 cases in Scotland show that one of them dates back to 11 January (the date of admission), but the remaining 12 cases were admitted to hospital in March and April [3].
In previous years, there were usually fewer than four people with unexplained hepatitis in Scotland, so Scotland issued a notice at the end of March [3].
At present, it is uncertain how fast the rate of unexplained hepatitis in children will increase [2].
The common hepatitis virus (hepatitis A to E virus) was not found in all children [2]. So who is the culprit?
Is it the coronavirus?
Dr Jean-Marc Sabatier, director of research at the French National Academy of Sciences, said that the acute hepatitis was similar to the pathophysiology of the new crown virus infection.
Some studies have shown that the new coronavirus invades cells with angiotensin-converting enzyme 2 (ACE2) as a receptor, causing ACE2 destruction, causing an imbalance in the renin-angiotensin system (RAS). Our liver cells, on the other hand, have ACE2 receptors on their surfaces, which are targets for the new coronavirus spike protein and the vaccine spike protein [4].
However, this is only a theoretical speculation and more research is needed.
Moreover, only 20 of the 169 children tested positive for COVID-19, and 19 of them were infected with both COVID-19 and adenovirus [2].
Therefore, the link between unexplained hepatitis in children and the new crown virus is not yet certain.
Is it a COVID-19 vaccine?
There are foreign reports [4] that there are risks of COVID-19 vaccines based on the Omiljung spike protein, and young children who receive the COVID-19 vaccine may have the same symptoms of liver inflammation.
The WHO's notification also responded to speculation about the pathogenesis of the new crown vaccine: the vast majority of children have not been vaccinated against the new crown [2].
Moreover, the majority of children who receive domestic COVID-19 vaccines in the mainland do not have such cases, so there is no need to worry about unexplained hepatitis in children caused by the new crown vaccine.
Is it an adenovirus?
The current mainstream view is more inclined to believe that the pathogen of this unknown hepatitis is "adenovirus", because adenovirus was detected in at least 74 people in 169 cases [2]. Also, in the UK, which has the highest number of cases, a significant increase in adenovirus infections has recently been observed [2].
(Adenovirus looks like under a microscope and its structural patterns.) Image source: Medical Microbiology (8th Edition))
Adenoviruses can be divided into seven subgroups A to G, with 42 serotypes, and can be transmitted by droplets, fecal-oral pathways, or contact. Symptoms vary from adenovirus infection to adenovirus infection, but are more commonly respiratory symptoms [5,6]. Hepatitis may also occur in immunocompromised patients, but is common in adenovirus type 5 [7].
Of the 74 children detected with adenovirus, 18 were adenovirus type 41, and patients with adenovirus type 41 infection had not previously experienced symptoms like this unexplained hepatitis [2]. Therefore, the determination of pathogens still needs more research.
Adenovirus as a vector for a COVID-19 vaccine is of concern, so there are also some opinions that this unexplained hepatitis may be related to the vaccination of adenovirus vectors against COVID-19. However, further analysis found that children with unexplained hepatitis had hardly been injected with any form of COVID-19 vaccine, so there is little correlation at present.
Combined with the above tests, there are several conjectures about the cause [2]:
During the COVID-19 epidemic, protective measures for susceptible populations have been strengthened, and transmission routes have been greatly cut off, resulting in a decrease in the level of adenovirus transmission, resulting in a relative decrease in antibody production in children who are rarely exposed to adenovirus, and thus increasing susceptibility to adenovirus.
A novel adenovirus may have emerged.
The new coronavirus is co-infected with adenovirus.
However, further verification is still required.
Of the 169 cases, the age range ranged from 1 month to 16 years [2]. In 13 cases in Scotland, 12 children were aged 5 years or younger [3]. Common symptoms in these children include [2]:
Gastrointestinal symptoms: abdominal pain, diarrhea, vomiting.
Significantly elevated alanine aminotransferase: Alanine aminotransferase levels are an important indicator of liver function. The enzyme normally ranges from 10 to 40 IU/L, reaching 500 IU/L in children and 4000 IU/L in some children[3]
Jaundice: Jaundice manifests as yellowing of the skin or sclera (whites of the eye) and is a common manifestation of liver disease and is caused by elevated serum bilirubin concentrations.
This time, unexplained hepatitis has a very great ability to destroy the liver function of the children, and about 10% of the children have needed liver transplantation, and one person has died.
Unfortunately, it is still uncertain whether the disease will be contagious. Countries currently reporting cases are screening a wider population and conducting epidemiological investigations.
Based on the WHO report, there is currently a relatively higher likelihood that adenovirus is the cause of unexplained hepatitis in children [2], so precautions for adenovirus will be introduced in this article.
Adenovirus infection is actually a relatively common disease, mainly in the spring and winter epidemic, infants, young children, the elderly and the immunocompromised belong to the susceptible group, kindergartens, universities, barracks and other places are prone to mass infection [6].
Adenovirus can be transmitted through droplets, fecal-oral routes or contact, but there is currently no vaccine against adenovirus in China, and can only be protected by personal hygiene (frequent hand washing, avoiding close contact with patients), wearing masks, etc.
In addition, some COVID-19 vaccines use adenovirus vector vaccines, but adenovirus vector vaccines will eliminate the genes associated with replication in adenoviruses, making it impossible for adenoviruses to replicate in vivo. Therefore, there is no need to worry about contracting adenovirus as a result of adenovirus vector vaccination.
The above is currently public information about the recent outbreak of unexplained hepatitis in children, and it is still unknown whether the disease will become a new large-scale infectious disease. No similar cases have been reported in the country at this time.
Some marketing numbers may be over-interpreted, creating rumors and panic. But there is no need for excessive anxiety until more research comes out.
Reviewer: Zhou Ning
Pediatrician of Shanghai Tongji Hospital
bibliography
[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://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 – Acute, severe hepatitis of unknown origin in children. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/multi-country-acute-severe-hepatitis-of-unknown-origin-in-children
[3] Marsh K, Tayler 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://frenchdailynews.com/society/4581-acute-childhood-hepatitis-a-link-with-covid-19.
Li Fan, Xu Zhikai. Medical Microbiology (8th Edition)[M]. People's Medical Publishing House, 2013: 248-249.
[6] Lin Guowei,Wang Jiyao,Ge Junbo. Practical Internal Medicine (15th Edition)[M]. People's Medical 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://www.uptodate.com/contents/zh-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