[Text/Observer Network Wang Hui] The new crown epidemic has not yet ended, and a mysterious hepatitis has suddenly appeared in many countries around the world, reaching out to children to "poison the hand".
So far, more than 200 children in 17 countries around the world have been recruited, and cases have been reported in the United Kingdom, the United States, Spain, Israel, France, and Japan. The current cases are mainly concentrated in Europe, with the UK being the largest, which has increased to 145.
According to Richard Pebodi, an infectious disease specialist at the WHO Regional Office for Europe, patients aged between 1 month and 16 years of age, require liver transplantation in about 10% of cases and at least 1 death.
What scares and even panics many people is that the cause of these hepatitis cases is still unknown and investigation is ongoing.
Chang Rongshan, a virology expert, told the Observer Network that according to his understanding, before the new crown, China found hundreds of cases of unexplained childhood hepatitis every year, and the cause of these children's hepatitis could neither find known pathogens nor be completely attributed to infection. Therefore, now that more than 200 cases have been reported overseas, it is within the normal range, and everyone does not have to panic.
He believes that this time unexplained hepatitis in children is unlikely to cause a large-scale epidemic like the new crown pneumonia. "Although the spread of infectious diseases in the digestive tract is not as strong as that of respiratory infectious diseases, if it is endemic, it will not be this magnitude, and a few thousand cases is the minimum."
Chang Rongshan said that in the post-epidemic era, as more and more countries open their doors, there may be more and more unexplained diseases in children in the future, and we need to pay great attention to it.
British children diagnosed with hepatitis of unknown cause in March Image: The Daily Mail
Is the "murderer" an adenovirus?
Since none of the five common hepatitis viruses A, B, C, D, and E have been detected in all cases, researchers in many countries have expanded the scope of viral screening to viruses that are not within the scope of routine testing for acute hepatitis, including enteroviruses, varicella zoster viruses, adenoviruses, etc.
Eventually, they found a new clue: adenovirus.
Of the 169 cases published by WHO, 74 children tested positive for adenovirus, of which 18 were identified as adenovirus type 41 (Ad41). 20 cases of children were tested for the new crown virus, and 19 cases were co-infected with adenovirus and the new crown virus.
On 25 April, the UK Health Security Agency (UKHSA) released a technical briefing on the investigation. Of the 53 cases tested, adenovirus was detected in 40, the briefing said. Based on blood sample data, the initial classification of adenovirus is type 41, but other types of adenovirus have also been found in non-blood samples. Whole genome sequencing of multiple cases is essential before determining viral characteristics. Although low levels of adenovirus in the blood are a challenge to data quality, this work is ongoing.
Uk healthcare data show that the current level of common virus transmission among children is currently higher than in previous years, with a significant increase in cases of adenovirus infection, especially in children aged 1 to 4 years.
Pathogen testing and results for cases in England Source: HEALTH Security Agency briefing on 25 April
According to a report released by the U.S. Centers for Disease Control and Prevention on April 29, between October 2021 and February 2022, Alabama reported a total of nine cases of acute hepatitis in children of unknown etiology. Prior to the onset of illness, these patients were generally in good health and had no record of confirmed COVID-19.
According to the center, adenoviruses were detected in blood samples from all patients, and when genetic sequencing was performed on the samples of 5 of them, adenoviruse type 41 was detected in all 5 samples.
Adenovirus is a common human pathogen, a double-stranded DNA virus, no envelope, divided into 7 subgroups (A-G subgroup), a total of 57 serotypes, mainly through respiratory tract and contact transmission from person to person, often causing respiratory diseases. Different serotypes of adenoviruses can cause other diseases such as gastroenteritis (inflammation of the stomach or intestines), conjunctivitis (pink eye), and cystitis.
Adenovirus type 41 is a common cause of acute gastroenteritis in children, "because it is less pathogenic and rarely causes hepatitis, and liver transplantation and even death in children like this is very rare." Chang Rongshan said.
Source: WeChat public account "Huashan infection"
Because the symptoms of these cases of hepatitis in children are not typical of adenovirus infection, experts are still investigating other possible causes, such as COVID-19 infection or environmental factors.
Will Owen, a professor of virology at the University of Nottingham in the United Kingdom, said adenovirus infection was a possibility but had not yet been confirmed. There are few case reports of adenovirus infection associated with immune-normal childhood or adult hepatitis in the global literature, so "if adenovirus infection is indeed found to be associated with outbreaks of this disease, there is a need to explain why the natural history of adenovirus infection has changed so dramatically in 2022".
The surge in hepatitis in children may be associated with prolonged lockdown
After humans are born, there are two ways to obtain immunity. One is passive immunity gained through natural infection/recovery, and the other is active immunization obtained through vaccination.
Chang Rongshan said that "there is no vaccine for adenovirus", so passive immunity can only be established in continuous contact.
The UK Health Security Agency put forward a hypothesis in the briefing on the 25th that the increase in hepatitis cases in children of unknown etiology may be a chain reaction of the new crown pandemic. Lockdowns and other restrictions mean that many children are exposed to less common viruses than normal during the COVID-19 pandemic, and as society reopens, they have an inadequate immune response to infection.
"Countries have adopted quarantine policies to prevent and control the new crown virus, wearing masks, maintaining social distancing, blocking the flow of people between countries and so on. This 'containment' has severely cut off the transmission route of the epidemic under normal circumstances, and the level of adenovirus transmission has been reduced. In general, adults have pre-existing antibodies to multiple human adenovirus serotypes. However, in recent years, the antibodies against human adenovirus in children who have rarely been exposed to adenovirus have decreased significantly, and children under 5 years of age generally lack passive immunity to adenovirus. Therefore, it is explainable that only 2 months after the liberalization of the countries in the northern hemisphere, in February-April of each year, when the adenovirus epidemic is high, some children were found to be infected and sick. Chang Rongshan said.
In September 2021, in Madrid, a teacher is taking the temperature of a student Image source: The Associated Press
He believes that in the post-COVID-19 era, there will be many unexplained infections in children, because long-term isolation policies have led to children not being exposed to various respiratory transmission viruses for a long time, which is not conducive to the development of the immune system, and it is difficult to produce various pre-stored neutralizing antibodies to resist the pathogens that are constantly encountered in the process of growth.
"In this sense, the best way to prevent epidemics is vaccines," Chang said, but the two common viruses associated with the respiratory tract, respiratory syncytial virus and adenovirus, have never been vaccinated, and the epidemic intensity in children is expected to increase in the future, and their case Fatality Rate (CFR) in children's population far exceeds the NEW CROWN CFR.
He called on all sectors of society to pay attention to children's viral pneumonia and increase the research and development of vaccines for children's infectious diseases. For the biomedical investment industry, this is a blue ocean market of the future. "As long as we spend a small fraction of our venture capital on developing these vaccines, we can greatly reduce the harm that these epidemics do to children."
Laboratory tests suggest that adenovirus may be associated with unexplained childhood hepatitis, but other infectious causes or environmental factors cannot be completely ruled out. Metagenomic sequencing and sequence analysis are still underway, and the results have not yet been published.
A few days ago, experts such as Xie Youhua, director of the Department of Pathogenic Biology of Fudan University's Basic Medical College of Basic Medical Sciences, professor of the Key Laboratory of Medical Molecular Virology, and vice president of the Shanghai Institute of Major Infectious Diseases and Biosafety, wrote an article in the journal "Microbiology and Infection", speculating that the possible causes of hepatitis in children of unknown causes are as follows:
1. It is a new variant of a known virus, which may be adenovirus, but it cannot rule out the possibility of other pathogens, such as coronavirus, rhinovirus, enterovirus, parainfluenza virus and other variant strains. If it is a new variant of adenovirus, it is worth paying attention to whether it is related to the recombination and mutation of adenovirus under the selection pressure that may occur after mass vaccination of adenovirus vector vaccine.
2. The prevention and control of the epidemic during the COVID-19 epidemic may cause some young children to have reduced contact with common pathogens, resulting in the development of their immune systems different from those of children of the same age before the COVID-19 epidemic. When young children are subsequently infected with common pathogens such as adenovirus, they have a different immune response or disease manifestation than their previous peers; it is also possible that subsequent infection with adenovirus or other viruses based on previous SARS-CoV-2 (new coronavirus) infection, or sars-CoV-2 co-infection with adenovirus or other viruses, may produce an unusual immune response or disease manifestations.
3. There is a new pathogen that has not yet been discovered.
4. Non-infectious factors, such as environmental toxins and drugs, cannot be completely ruled out.
Are children on the mainland at risk of infection? What should parents do?
With the exposure of unexplained cases of childhood hepatitis in many countries, recently, news similar to "cases of unexplained childhood hepatitis in Beijing" has not gone away on the Internet.
In response to various rumors, on the afternoon of April 27, the official microblog of the Beijing Municipal Health Commission said that after verification by the Beijing Municipal Health Commission, there were no cases of unexplained childhood hepatitis and the resulting deaths in Beijing.
Despite this, experts such as Xie Youhua reminded that whether there is similar unexplained childhood hepatitis on the mainland still needs to be investigated. According to the criteria for confirmed cases, the occurrence of hepatitis of unknown cause in the mainland (hepatitis A, B, C, D and E) can be collected since January 1, 2022, compared with the data of previous years, and whether there is also an increase in hepatitis cases in children of unknown cause in the mainland. On the other hand, because of the imported risk of the disease, preparation must be made early. Given the differences in immunization backgrounds and prevalent pathogens in different countries and regions, it is not possible to assess the risk of disease caused by exposure to this pathogen in mainland children at this stage.
As for personal protection, Chang Rongshan mentioned that the main means of preventing adenovirus infection include washing hands frequently, avoiding touching the eyes, nose and mouth with unclean hands, and avoiding close contact with patients.
He suggested that children should be widely vaccinated with safe and effective COVID-19 vaccines, such as recombinant protein vaccines, so that children aged 0-5 years can remove their masks as soon as possible. "Otherwise, the child's immune system cannot develop properly. Attacks by a variety of pathogens through the respiratory tract are indispensable 'tempering' for children in their growth, the flowers in the greenhouse are destined to be unable to withstand wind and rain, and the small chance of infection falling on a child's head is a big stone. ”
Chang Rongshan said that at present, parents should remain calm and rationally look at the various remarks on the Internet that link this rare disease to new crown pneumonia. He said there was no direct evidence that the study had reported the link between acute hepatitis and covid-19 infection. In addition, WHO also informed that since the vast majority of children have not been vaccinated against COVID-19, the hypothesis that acute hepatitis is related to the side effects of the COVID-19 vaccine is not currently supported.
According to the symptoms of existing cases, parents should pay close attention to whether their children have these manifestations, and once found, they need to seek medical attention in time:
· Diarrhea, abdominal pain;
· Vomiting, nausea, not wanting to eat;
· Discoloration of urine or feces;
· Usually accompanied by jaundice (pale yellow of the skin and white eyeball);
· Fatigue, pain in the hepatic region;
· Bleeding gums when brushing teeth, bruised ecchymosis on the body;
· Itching of the skin;
· Significantly elevated liver enzymes;
· Most children do not have symptoms of fever.