Suspected Adenovirus Causing an Emerging HEPATITIS among Children below 10 Years: A Review

Ali A Rabaan 1 2 3, Muhammed A Bakhrebah 4, Majed S Nassar 4, Zuhair S Natto 5, Abbas Al Mutair 6 7 8 9, Saad Alhumaid 10, Mohammed Aljeldah 11, Mohammed Garout 12, Wadha A Alfouzan 13 14, Fatimah S Alshahrani 15 16, Tarek Sulaiman 17, Meshal K AlFonaisan 18, Mubarak Alfaresi 19 20, Saleh A Alshamrani 21, Firzan Nainu 22, Shin Jie Yong 23, Om Prakash Choudhary 24, Naveed Ahmed 25

Affiliations

21 June 2022

-

doi: 10.3390/pathogens11070712

Abstract

In October 2021, a case of acute hepatic failure without any known cause was identified in the United States of America. Upon further investigation, other children aged 1-6 years were reported to have the same liver failure, and some of them were positive for adenovirus 41 type F. On 21 April 2022, the Centers for Disease Control and Prevention (CDC) released an alert after 74 cases were identified in United Kingdom (UK) between 5 and 8 April in children below 10 years of age, some of whom were also found to be positive for SARS-CoV-2. All the patients showed symptoms such as vomiting, diarrhea, jaundice, and abdominal pain. The patients' liver enzymes were remarkably increased. A total of 650 cases had been reported from 33 countries as of 27 May 2022, among which 222 cases were reported in the UK alone. No connection with SARS-CoV-2 or its vaccine has been found so far. However, the suspected cause is adenovirus, including its genomic variations, because its pathogenesis and laboratory investigations have been positively linked. Until further evidence emerges, hygiene precautions could be helpful to prevent its spread.

Keywords: acute hepatitis; adverse effects; autoimmune hepatitis; liver inflammation; molecular mimicry; pathology.

Conflict of interest statement

The authors declare no conflict of interest.

Similar articles

Acute hepatitis (Non Hepa A-E) of unknown origin among pediatrics.

Asadi Faezi N, Mehramouz B, Taghizadeh S, Pagliano P, Kafil HS.Infez Med. 2022 Sep 1;30(3):353-361. doi: 10.53854/liim-3003-4. eCollection 2022.PMID: 36148173 Free PMC article. Review.

Emerging Variants of SARS-CoV-2 And Novel Therapeutics Against Coronavirus (COVID-19).

Aleem A, Akbar Samad AB, Vaqar S.2023 Feb 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–.PMID: 34033342 Free Books & Documents.

May 2022 acute hepatitis outbreak, is there a role for COVID-19 and other viruses?

Elbeltagi R, Al-Beltagi M, Saeed NK, Bediwy AS, Toema O.World J Hepatol. 2023 Mar 27;15(3):364-376. doi: 10.4254/wjh.v15.i3.364.PMID: 37034240 Free PMC article. Review.

Diagnosis, treatment, and prevention of severe acute hepatitis of unknown etiology in children.

Chen YH, Lou JG, Yang ZH, Chen QJ, Hua CZ, Ye S, Zhang CM, Chen J, Huang ZW, Yu JD, Gao ZG, Shu Q.World J Pediatr. 2022 Aug;18(8):538-544. doi: 10.1007/s12519-022-00581-x. Epub 2022 Jun 30.PMID: 35771382 Free PMC article. Review.

Severe acute hepatitis of unknown etiology in children in 2022: A Narrative Review.

Namakin K, Naserghandi A, Allameh SF.New Microbes New Infect. 2023 Jan 21;51:101087. doi: 10.1016/j.nmni.2023.101087. eCollection 2023 Jan.PMID: 36755794 Free PMC article. Review.

Cited by

A Novel Approach to Develop New and Potent Inhibitors for the Simultaneous Inhibition of Protease and Helicase Activities of HCV NS3/4A Protease: A Computational Approach.

Riaz M, Rehman AU, Waqas M, Khalid A, Abdalla AN, Mahmood A, Hu J, Wadood A.Molecules. 2023 Jan 29;28(3):1300. doi: 10.3390/molecules28031300.PMID: 36770965 Free PMC article.

Acute hepatitis (Non Hepa A-E) of unknown origin among pediatrics.

Asadi Faezi N, Mehramouz B, Taghizadeh S, Pagliano P, Kafil HS.Infez Med. 2022 Sep 1;30(3):353-361. doi: 10.53854/liim-3003-4. eCollection 2022.PMID: 36148173 Free PMC article. Review.

Human Mastadenovirus Infections in Children: A Review of the Current Status in the Arab World in the Middle East and North Africa.

Qashqari FSI.Children (Basel). 2022 Sep 6;9(9):1356. doi: 10.3390/children9091356.PMID: 36138665 Free PMC article. Review.

References

  1.  
    1. Centers for Disease Control and Prevention (CDC) Recommendations for Adenovirus Testing and Reporting of Children with Acute Hepatitis of Unknown Etiology. [(accessed on 25 April 2022)];2022 April 21; Available online: https://emergency.cdc.gov/han/2022/han00462.asp.
  2.  
    1. Ghany M.G., Liang T.J. Acute viral hepatitis. Yamada’s Textb. Gastroenterol. 2022:1804–1840. doi: 10.1002/9781119600206.ch86. - DOI
  3.  
    1. Gu J., Su Q.-Q., Zuo T.-T., Chen Y.-B. Adenovirus diseases: A systematic review and meta-analysis of 228 case reports. Infection. 2021;49:1–13. doi: 10.1007/s15010-020-01484-7. - DOI - PMC - PubMed
  4.  
    1. Baker J.M., Buchfellner M., Britt W., Sanchez V., Potter J.L., Ingram L.A., Shiau H., Sanchez L.H.G., Saaybi S., Kelly D., et al. Acute Hepatitis and Adenovirus Infection Among Children—Alabama, October 2021–February 2022. [(accessed on 16 June 2022)];Morb. Mortal. Wkly. Rep. 2022 doi: 10.15585/mmwr.mm7118e1. Available online: https://www.cdc.gov/mmwr/volumes/71/wr/mm7118e1.htm?s_cid=mm7118e1_w. - DOI - PMC - PubMed
  5.  
    1. Khalifa A., Andreias L., Velpari S. Adenovirus Hepatitis in Immunocompetent Adults. J. Investig. Med. High Impact Case Rep. 2022;10:23247096221079192. doi: 10.1177/23247096221079192. - DOI - PMC - PubMed
  6.  
    1. Public Health Scotland COVID-19 Statistical Report 6 April 2022. Edinburgh: Public Health Scotland. [(accessed on 12 May 2022)]. Available online: https://publichealthscotland.scot/publications/covid-19-statistical-repo...
  7.  
    1. World Health Organization Disease Outbreak News: Multi-Country—Acute, Severe Hepatitis of Unknown Origin in Children. Apr 23, 2022. [(accessed on 25 April 2022)]. Available online: https://www.who.int/emergencies/disease-outbreak-news/item/multi-country....
  8.  
    1. Sallam M., Mahafzah A., Şahin G.Ö. Clusters of Hepatitis of Unknown Origin and Etiology (Acute Non HepA–E Hepatitis) Among Children in 2021/2022: A Review of the Current Findings. Healthcare. 2022;10:973. doi: 10.3390/healthcare10060973. - DOI - PMC - PubMed
  9.  
    1. Samarasekera U. Mystery outbreak of severe acute hepatitis in children. Lancet Gastroenterol. Hepatol. 2022;7:601. doi: 10.1016/S2468-1253(22)00159-5. - DOI
  10.  
    1. Christie B. Scientists search for cause of hepatitis cases in children. BMJ. 2022;377:o982. doi: 10.1136/bmj.o982. - DOI - PubMed
  11.  
    1. European Centre for Disease Prevention and Control Rapid Risk Assessment: Increase in Severe Acute Hepatitis Cases of Unknown Aetiology in Children—28 April 2022. ECDC, Stockholm. [(accessed on 29 April 2022)]. Available online: https://www.ecdc.europa.eu/en/publications-data/increase-severe-acute-he....
  12.  
    1. Scottish Government COVID-19 Scotland’s Strategic Framework Update 2022. Edinburgh: Scottish Government. [(accessed on 12 May 2022)]; Available online: https://www.gov.scot/binaries/content/documents/govscot/publications/str....
  13.  
    1. Zhu Z., Zhang N., Mao Y., Xu W. Consideration on the emerging of severe acute hepatitis cases with of unknown etiology in children worldwide. Zhonghua Yu Fang Yi Xue Za Zhi [Chin. J. Prev. Med.] 2022;56:1–3. - PubMed
  14.  
    1. Jalilian M. Viral Hepatitis and COVID-19: A Systematic Review on the Current Evidences. Govaresh. 2022;26:184–194.
  15.  
    1. Zhou X., Song X., Wan L. Epstein-Barr Virus Encephalitis and Disseminated Adenovirus Infection after Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for a Patient with Ph-Like Acute Lymphoblastic Leukemia. Case Rep. Oncol. 2022;15:245–250. doi: 10.1159/000522556. - DOI - PMC - PubMed
  16.  
    1. Jonsdottir S., Arnardottir M.B., Andresson J.A., Bjornsson H.K., Lund S.H., Bjornsson E.S. Prevalence, clinical characteristics and outcomes of hypoxic hepatitis in critically ill patients. Scand. J. Gastroenterol. 2022;57:311–318. doi: 10.1080/00365521.2021.2005136. - DOI - PubMed
  17.  
    1. UK Health Security Agency Technical Briefing: Investigation into Acute Hepatitis of Unknown Aetiology in Children in England, Version 1.0. [(accessed on 27 April 2022)];2022 April 25; GOV-12076. Available online: https://www.gov.uk/government/publications/acute-hepatitis-technical-bri....
  18.  
    1. Khan Y.H., Mallhi T.H., Alanazi A.S., Butt M.H., Khan A., Salman M. Outbreak of Acute Hepatitis of Unknown etiology in Children; The Critical Role of Healthcare Professionals in Neutralizing Misleading Narratives during the COVID-19 Pandemic. J. Med. Virol. 2022:1–2. doi: 10.1002/jmv.27819. - DOI - PMC - PubMed
  19.  
    1. Cao W., Li Z., Zhu H., Zhou X., Yang Q., Han Y., Liu J., Chang Q., Li T. Diagnosis and Clinical Management of Acute Severe Hepatitis of Unknown Origin: Operational Recommendation of Peking Union Medical College Hospital. Infect. Dis. Immun. 2022;2:E002.
  20.  
    1. Aricò M., Caselli D. Acute, Severe Hepatitis of Unknown Origin: Should We Really Be Afraid of Another Obscure Enemy of Our Children? Pediatric Rep. 2022;14:217–219. doi: 10.3390/pediatric14020029. - DOI - PMC - PubMed
  21.  
    1. European Centre for Disease Prevention and Control Update: Hepatitis of Unknown Origin in Children. [(accessed on 25 April 2022)]. Available online: https://www.ecdc.europa.eu/en/news-events/update-hepatitis-unknown-origi....
  22.  
    1. World Health Organization Disease Outbreak News: Acute Hepatitis of Unknown Aetiology—The United Kingdom of Great Britain and Northern Ireland. Apr 15, 2022. [(accessed on 25 April 2022)]. Available online: https://www.who.int/emergencies/disease-outbreak-news/item/acute-hepatit....
  23.  
    1. World Health Organization Disease Outbreak News; Acute Hepatitis of Unknown Aetiology in Children—Multi-Country. [(accessed on 27 May 2022)]. Available online: https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON389.
  24.  
    1. Mücke M.M., Zeuzem S. The recent outbreak of acute severe hepatitis in children of unknown origin—What is known so far. J. Hepatol. 2022;77:237–242. doi: 10.1016/j.jhep.2022.05.001. - DOI - PubMed
  25.  
    1. AL-Bashar S.H., Badawy A.S., Mohammed B.A.-R. Laboratory Diagnosis of Human Adenovirus associated with Respiratory Tract Infection in children. Tikrit J. Pure Sci. 2022;27:9–21. doi: 10.25130/j.v27i1.1243. - DOI
  26.  
    1. Khattak Z., Shah A.A., Zaidi S.S.Z., Mahmood N., Alam M.M., Sharif S., Akhtar R., Arshid Y., Rana M.S. Isolation and molecular characterization of Adenovirus in suspected acute flaccid paralysis patients: A preliminary report from Pakistan. Arch. Virol. 2022;167:483–491. doi: 10.1007/s00705-021-05346-x. - DOI - PubMed
  27.  
    1. Marsh K., Tayler R., Pollock L., Roy K., Lakha F., Ho A., Henderson D., Divala T., Currie S., Yirrell D. Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022. Eurosurveillance. 2022;27:2200318. doi: 10.2807/1560-7917.ES.2022.27.15.2200318. - DOI - PMC - PubMed
  28.  
    1. Kolavic-Gray S.A., Binn L.N., Sanchez J.L., Cersovsky S.B., Polyak C.S., Mitchell-Raymundo F., Asher L.V., Vaughn D.W., Feighner B.H., Innis B.L. Large epidemic of adenovirus type 4 infection among military trainees: Epidemiological, clinical, and laboratory studies. Clin. Infect. Dis. 2002;35:808–818. doi: 10.1086/342573. - DOI - PubMed
  29.  
    1. Mahase E. Hepatitis in children: What’s behind the outbreaks? BMJ. 2022;377:o1067. doi: 10.1136/bmj.o1067. - DOI - PubMed
  30.  
    1. Kujawski S.A., Lu X., Schneider E., Blythe D., Boktor S., Farrehi J., Haupt T., McBride D., Stephens E., Sakthivel S.K. Outbreaks of adenovirus-associated respiratory illness on 5 college campuses in the United States, 2018–2019. Clin. Infect. Dis. 2021;72:1992–1999. doi: 10.1093/cid/ciaa465. - DOI - PMC - PubMed
  31.  
    1. Miller N.J., Hooper D.R., Sharma A. Bilateral neuralgic amyotrophy in a patient with livestock-associated hepatitis E virus infection. CMAJ. 2022;194:E495–E499. doi: 10.1503/cmaj.211679. - DOI - PMC - PubMed
  32.  
    1. Montvydaite M., Seskute G., Minseviciute G., Svetikas L., Miltiniene D., Selickaja S., Butrimiene I. The manifestation of myositis in tick-borne encephalitis as a prophet of severe disease course: A rare case report. Clin. Rheumatol. 2022;41:1241–1245. doi: 10.1007/s10067-022-06058-6. - DOI - PubMed
  33.  
    1. Musto J., Stanfield D., Ley D., Lucey M.R., Eickhoff J., Rice J.P. Recovery and outcomes of patients denied early liver transplantation for severe alcohol-associated hepatitis. Hepatology. 2022;75:104–114. doi: 10.1002/hep.32110. - DOI - PubMed
  34.  
    1. Rivero-Juarez A., Frias M., Perez A.B., Pineda J.A., Reina G., Fuentes-Lopez A., Freyre-Carrillo C., Ramirez-Arellano E., Alados J.C., Rivero A. Orthohepevirus C infection as an emerging cause of acute hepatitis in Spain: First report in Europe. J. Hepatol. 2022;12:S0168-8278(22)00075-7. doi: 10.1016/j.jhep.2022.01.028. - DOI - PubMed
  35.  
    1. Tüfekçi Ö., Özdemir H.H., Malbora B., Özbek N.Y., Yarali N., Erdem A., Evim M., Baytan B., Güneş A.M., Karapinar T. Hepatitis-associated aplastic anemia: Etiology, clinical characteristics and outcome. J. Pediatric Hematol./Oncol. 2022;44:e223–e226. doi: 10.1097/MPH.0000000000002268. - DOI - PubMed
  36.  
    1. Siva N. Hunt begins for the cause of acute hepatitis cases. Lancet. 2022;399:1765. doi: 10.1016/S0140-6736(22)00818-2. - DOI - PubMed
  37.  
    1. Putra J., Ng V.L., Perez-Atayde A.R. Pediatric Acute Liver Failure: A Clinicopathological Perspective. Pediatric Dev. Pathol. 2022:10935266211067893. doi: 10.1177/10935266211067893. - DOI - PubMed
  38.  
    1. Office for National Statistics . Coronavirus (COVID-19) Infection Survey: Scotland. Office for National Statistics; London, UK: 2022. [(accessed on 12 April 2022)]. Available online: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/....
  39.  
    1. Hasham K., Ahmed N., Zeshan B. Circulating microRNAs in oncogenic viral infections: Potential diagnostic biomarkers. SN Appl. Sci. 2020;2:442. doi: 10.1007/s42452-020-2251-0. - DOI
  40.  
    1. Schaberg K.B., Kambham N., Sibley R.K., Higgins J. Adenovirus hepatitis. Am. J. Surg. Pathol. 2017;41:810–819. doi: 10.1097/PAS.0000000000000834. - DOI - PubMed
  41.  
    1. Goetting J., Cordes A.K., Steinbrueck L., Heim A. Molecular Phylogeny of human adenovirus type 41 lineages. bioRxiv. 2022 doi: 10.1101/2022.05.30.493978. - DOI
  42.  
    1. Lee B., Damon C.F., Platts-Mills J.A. Pediatric acute gastroenteritis due to adenovirus 40/41 in low-and middle-income countries. Curr. Opin. Infect. Dis. 2020;33:398. doi: 10.1097/QCO.0000000000000663. - DOI - PMC - PubMed
  43.  
    1. Slatter M.A., Read S., Taylor C.E., Crooks B.N., Abinun M., Flood T.J., Cant A.J., Wright C., Gennery A.R. Adenovirus type F subtype 41 causing disseminated disease following bone marrow transplantation for immunodeficiency. J. Clin. Microbiol. 2005;43:1462–1464. doi: 10.1128/JCM.43.3.1462-1464.2005. - DOI - PMC - PubMed
  44.  
    1. Gaensbauer J.T., Lamb M., Calvimontes D.M., Asturias E.J., Kamidani S., Contreras-Roldan I.L., Dominguez S.R., Robinson C.C., Zacarias A., Berman S. Identification of enteropathogens by multiplex PCR among rural and urban Guatemalan children with acute diarrhea. Am. J. Trop. Med. Hyg. 2019;101:534. doi: 10.4269/ajtmh.18-0962. - DOI - PMC - PubMed
  45.  
    1. Arowolo K.O., Ayolabi C.I., Lapinski B., Santos J.S., Raboni S.M. Epidemiology of enteric viruses in children with gastroenteritis in Ogun State, Nigeria. J. Med. Virol. 2019;91:1022–1029. doi: 10.1002/jmv.25399. - DOI - PubMed
  46.  
    1. Pratte-Santos R., Miagostovich M.P., Fumian T.M., Maciel E.L., Martins S.A., Cassini S.T., Keller R. High prevalence of enteric viruses associated with acute gastroenteritis in pediatric patients in a low-income area in Vitória, Southeastern Brazil. J. Med. Virol. 2019;91:744–750. doi: 10.1002/jmv.25392. - DOI - PubMed
  47.  
    1. Gelaw A., Pietsch C., Liebert U.G. Genetic diversity of human adenovirus and human astrovirus in children with acute gastroenteritis in Northwest Ethiopia. Arch. Virol. 2019;164:2985–2993. doi: 10.1007/s00705-019-04421-8. - DOI - PubMed
  48.  
    1. Qiu F.-Z., Shen X.-X., Li G.-X., Zhao L., Chen C., Duan S.-X., Guo J.-Y., Zhao M.-C., Yan T.-F., Qi J.-J. Adenovirus associated with acute diarrhea: A case-control study. BMC Infect. Dis. 2018;18:1–7. doi: 10.1186/s12879-018-3340-1. - DOI - PMC - PubMed
  49.  
    1. Kumthip K., Khamrin P., Ushijima H., Maneekarn N. Enteric and non-enteric adenoviruses associated with acute gastroenteritis in pediatric patients in Thailand, 2011 to 2017. PLoS ONE. 2019;14:e0220263. doi: 10.1371/journal.pone.0220263. - DOI - PMC - PubMed
  50.  
    1. Arashkia A., Bahrami F., Farsi M., Nejati B., Jalilvand S., Nateghian A., Rahbarimanesh A., Shoja Z. Molecular analysis of human adenoviruses in hospitalized children < 5 years old with acute gastroenteritis in Tehran, Iran. J. Med. Virol. 2019;91:1930–1936. - PubMed
  51.  
    1. Myers V., Saban M., Wilf-Miron R. COVID-19 in children aged 5–11: Examining the issues surrounding vaccination and public health policy. Paediatr. Respir. Rev. 2022:S1526-0542(22)00031-8. doi: 10.1016/j.prrv.2022.03.002. - DOI - PMC - PubMed
  52.  
    1. Children and COVID-19: State-Level Data Report. American Academy of Pedeatrics. [(accessed on 16 June 2022)]. Available online: https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/
  53.  
    1. Molteni E., Sudre C.H., Canas L.D.S., Bhopal S.S., Hughes R.C., Chen L., Deng J., Murray B., Kerfoot E., Antonelli M., et al. Illness Characteristics of COVID-19 in Children Infected with the SARS-CoV-2 Delta Variant. Children. 2022;9:652. doi: 10.3390/children9050652. - DOI - PMC - PubMed

Page Navigation