The COVID-19 epidemic has not yet subsided, and mysterious hepatitis has broken out all over the world, quickly reaching out "poisonous hands" to children.
On 5 April 2022, the International Health Regulations (IHR) National Focal Point (NFP) for the United Kingdom first notified WHO of 10 cases of severe acute hepatitis of unknown aetiology young children (age range: 11 months to five-year-old)1. The situation then intensified and as of 26 May 2022, six hundred and fifty probable cases of acute hepatitis of unknown aetiology in children had been reported to WHO from 33 countries in five WHO Regions2. At the same time, both the UK Health Security Agency (UKHSA) and the US Centers for Disease Control and Prevention (CDC) reported that adenovirus was most frequently detected in the detection of diseased samples, suggesting that adenovirus may be an important factor in the occurrence of acute hepatitis in children of unknown cause.
1. What is adenovirus?
Adenoviruses are medium-sized (90~100nm), non-enveloped, icosahedral viruses composed of a nucleocapsid and a linear, double-stranded DNA (dsDNA) genome (Figure 1). It was first isolated in 1953 by Rowe WP et al. from the atrophic adenoid tissue, which was resected from patients, and belongs to the genus of mammalian adenovirus. It can be transmitted from patients and latently infected persons to others through droplet transmission, contact transmission and fecal-oral transmission, and is highly contagious.
Figure 1: The structure of Human adenovirus
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With the development of molecular biology technology, 52 serotypes of human adenovirus have been found, belonging to 7 different subgenus A-G. Different human adenoviruses have different tissue tropisms in the human body, and can infect the respiratory tract, intestinal tract and other organs and cause a variety of diseases (Table 1).
Table 1: Adenovirus serotypes and associated clinical diseases
2. Adenovirus infection
Adenovirus infection is a contagious viral disease, caused by Adenoviruses, commonly resulting in a respiratory tract infection3 (Figure 2). Human adenovirus infection is widely prevalent in the world, and the epidemic pattern is changeable. It is often related to factors such as the type of human adenovirus, the endemic area, and the age of susceptible people. It can occur all year round, especially in winter and spring4. Its typical symptoms range from the common cold (e.g. nasal congestion, coryza and cough) to respiratory inflammation (e.g. pneumonia)5. Laboratory tests are usually not required, and only signs and symptoms are required for diagnosis6. In some cases, PCR testing of blood or respiratory secretions may detect adenovirus DNA7.
Figure 2: Adenovirus causes respiratory infections
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3. Unknown acute hepatitis and Adenovirus
According to the latest WHO report, as of 27 May 2022, 181 cases were tested for adenovirus by any specimen type, of which 110 (60.8%) tested positive. The positivity rate was the highest in whole blood specimens (69.5%)2.
Recently, a paper published in The Lancet Gastroenterology & Hepatology put forward a conjecture: after the child was infected with the COVID-19, some components of the COVID-19 formed superantigens8. At the same time, the child happened to be infected with the adenovirus. Based on the above conditions, it is speculated that cases of unknown hepatitis in children may be related to this dual factor. As of May 13, 70% of reported cases of unexplained childhood hepatitis in Europe had been infected with the new coronavirus. Of the 12 cases detected in Israel, 11 had contracted the virus within a year.
4. Is "COVID-19 + Adenovirus" the "Real Culprit" ? This question remains to be confirmed
In response to this unknown childhood hepatitis epidemic, the guidance document issued by the UK Health Safety Agency (UKHSA) clearly recommends that confirmed cases should be tested for corresponding pathogenic microorganisms including adenovirus9.
At the same time, the US CDC also issued Clinical Guidance for Adenovirus Testing and Typing of Patients Under Investigation10. The guidance document states:
- A standard diagnostic workup for children with acute hepatitis should be done locally per treating clinicians.
- Consider testing for adenovirus in the evaluation of children with acute hepatitis of unknown cause.
5. Vazyme offers total solutions for adenovirus
Since the outbreak of unknown childhood hepatitis, countless IVD companies around the world have begun to develop adenovirus nucleic acid detection kits. As a supplier of professional products and solutions in life sciences, vitro diagnostics and biomedicine, Vazyme will give full play to the advantages in raw materials. In the field of adenovirus diagnosis, we provide you with a complete set of solutions including amplification reagents, positive reference and primer probe design for product development to help you quickly generate new products.
|Nucleic Acid Isolation|
|Magnetic bead-based||RM411||Virus DNA/RNA Extraction Kit 2.0 (Prepackaged)||Strong compatibility;
14 min fast extraction
|RM305ME||Virus DNA/RNA Extraction Kit||6 min rapid isolation and purification of nucleic acids|
|Column-based||RC313-CS||FastPure Viral DNA/RNA Mini Kit Pro||Compatible and fast|
Nucleic acid amplification
▶ Fully Validated Primer-Probe System
|Human adenovirus 1,2,3,4,5,6,7,11,14,15,16,55,66,68||Human adenovirus 40,41||IC|
▶ Amplification raw materials:
|qPCR Mix||QN213||Taq Pro U+ Multiple Probe qPCR Mix||Wide Compatibility;
Support Rapid Amplification;
High Sensitivity & Specificity.
|QV114||Animal Detection U+ Probe qPCR Super PreMix||High sensitivity qPCR master mix;
Support primer-probe full premix;
Support rapid procedures.
|Hot-start Polymerase||P132||Taq HS DNA Polymerase||Antibody-modified;
High sensitivity & ultra-tolerant;
Suitable for multiple reactions.
|Hot-sensitivity UDG||P051||Heat-labile UDG||The whole platform is anti-pollution matching system;
Rapidly inactive at 55°C for 10 min;
Compatible with common PCR reaction systems.
|Monoclonal Antibody||P121||Champagne Taq antibody||High specificity;
Thermostable Taq monoclonal antibody with extremely high purity and batch stability.
Product performance display
Taq Pro U+ Multiple Probe qPCR Mix（QN213）(click to view the product detail)
▶ Excellent amplification performance
At present, the etiology of the unknown childhood hepatitis epidemic has not been fully elucidated, and its etiological hypothesis mainly focuses on adenovirus infection, and the relationship with the COVID-19 also needs to be further investigated.
Vazyme provides fast nucleic acid extraction reagents and high-sensitivity, high-specific RT-qPCR related products, which can meet the relevant requirements of fast nucleic acid detection of COVID-19, and can also meet the multiple joint inspections of the COVID-19 + adenovirus + other respiratory pathogens.
|One step qPCR Master Mix|
|Q225||HiScript III U+ One Step qRT-PCR Probe Kit||Conventional;
Compatible with part of rapid programs
|Q231||AccurSTART U+ One Step RT-qPCR Probe Kit||Coming soon||Better compatibility;
Resistant to pseudovirus, oral and naspoharyngeal swabs
|P073||RoomTemp Sample Lysis Kit||Coming soon||Conventional chemical cracking;
At the same time, in order to meet customers' needs for more convenient, fast and stable raw materials, Vazyme is working on the raw material development of "primer-probe pre-mixing + rapid amplification", and we look forward to your continued attention about our latest updates.
1. Acute hepatitis of unknown aetiology – the United Kingdom of Great Britain and Northern Ireland. (2022). Retrieved 2 June 2022, from https://www.who.int/emergencies/disease-outbreak-news/item/ 2022-DON368
2. Acute hepatitis of unknown aetiology in children - Multi-country. (2022). Retrieved 2 June 2022, from https://www.who.int/emergencies/disease-outbreak-news/item/DON-389
3. Adenoviruses Home (2022). Retrieved 2 June 2022, from https://www.cdc.gov/adenovirus/hcp/clinical -overview.html
4. Lynch III, J. P., & Kajon, A. E. (2016, August). Adenovirus: epidemiology, global spread of novel serotypes, and advances in treatment and prevention. In Seminars in respiratory and critical care medicine (Vol. 37, No. 04, pp. 586-602). Thieme Medical Publishers.
5. Goldman, L., & Schafer, A. I. (2011). Goldman's cecil medicine E-book. Elsevier Health Sciences.
6. Tesini, Brenda L. (April 2022). "Adenovirus Infections - Infectious Diseases". MSD Manual Professional Edition. Retrieved 7 May 2022.
7. Arnold, A., & MacMahon, E. (2021). Adenovirus infections. Medicine, 49(12), 790-793.
8. The Lancet Infectious Diseases,Explaining the unexplained hepatitis in children,Volume 22, Issue 6, 2022,Page 743,ISSN 1473-3099,https://doi.org/10.1016/S1473-3099(22)00296-1.
9. Increase in hepatitis (liver inflammation) cases in children under investigation. (2022). Retrieved 2 June 2022, from https://www.gov.uk/government/news/increase-in-hepatitis-liver-inflammation-cases- in-children-under-investigation
10. National Center for Immunization and Respiratory Diseases (2022). Retrieved 2 June 2022, from https://www.cdc.gov/ncird/investigation/hepatitis-unknown-cause/hcp.html