Summary
A recent investigation by UK scientists reveals a potential cause for a concerning outbreak of acute hepatitis in children, linked to a previously under-monitored virus known as adeno-associated virus type 2. This virus typically requires co-infection with other viruses, such as adenoviruses or herpes viruses, to cause severe liver inflammation. The study suggests that children who experienced lockdowns during the COVID-19 pandemic may have missed early exposure to these common viruses, leading to a lack of immunity and increased susceptibility to severe infections later on.
The outbreak has affected children primarily under the age of five, with symptoms including pale stools, dark urine, jaundice, and general malaise. Hospitalization rates have been high, and some cases have required liver transplants. Researchers emphasize the need for larger studies to confirm these findings and to monitor the seasonal circulation of the adeno-associated virus, which has not been routinely tracked in the past. The scientists also note a possible genetic predisposition among affected children, indicating that a combination of environmental and genetic factors may play a role in the outbreak.
As the situation develops, experts urge parents to be vigilant for symptoms of hepatitis and to maintain good hygiene practices, although they acknowledge the challenges of doing so with young children. The findings underscore the importance of understanding viral interactions and the implications of public health measures on childhood immunity.
Show Notes
Serious hepatitis outbreak in children, immunity was NOT generated as normal in locked down children and now the specific viral cause has just been discoveredUploaded 26-07-22https://www.hpsc.ie/a-z/hepatitis/acutehepatitisofunknownaetiology/casedefinition/Since 20th MarchChildren under 16 35 countriesUK, 12 liver transplants, Ireland 2Immunosuppressant drugs for lifeNo single virus had been identified in all caseshttps://www.hpsc.ie/news/acute-hepatitis-of-unknown-cause-in-children.htmlHepatitis viruses A, B, C, E not detected in casesNo link to current covid infection statusMost / many cases were not covid vaccinatedSymptoms of hepatitisAny one of the classic 3Pale, grey-coloured stoolsDark urineJaundiceOther symptoms includemuscle and joint painfever feeling and being sickfeeling unusually tired all the timea general sense of feeling unwellloss of appetitetummy painitchy skinA post lockdown phenomena?Two common viruses, spreading again after pandemic lockdownsinfants exposed later than normalhttps://www.medrxiv.org/content/10.1101/2022.07.19.22277425v1Detailed investigation, 9 early cases and 58 control subjectsMedian 3.9 years, 4 boys, 5 girlsPreceding subacute historyAbdominal pain, diarrhoea and vomiting, between 1 to 11 weeks prior to acute hepatitisUsing sequencing and real-time PCRAdeno-associated virus 2 (AAV2), detected in the plasma of 9/9and liver of 4/4 patients(normally causes no illness, requires a coinfecting "helper" virus)Age-matched healthy controlsAdeno-associated virus 2 (AAV2), detected in the plasma of 0/13Children with adenovirus (HAdV) infection and normal liver functionAdeno-associated virus 2 (AAV2), detected in the plasma of 0/12Children admitted to hospital with hepatitis of other aetiologyAdeno-associated virus 2 (AAV2), detected in the plasma of 0/33AAV2 typically requires a coinfecting ‘helper’ virus to replicateUsually adenovirus (HAdV) or a herpesvirusAdenovirus (HAdV)Detected in 6/9 casesHuman herpesvirus 6B (HHV6B)Detected in 3/9 casesConclusionAcute non-A-E paediatric hepatitis is associated with the presence of Adeno-associated virus 2 (AAV2) infection,which could represent a primary pathogen or a useful biomarker of recent Adenovirus (HAdV) or Herpesvirus (HHV6B) infection. Prof Judith Breuer, University College London and Great Ormond Street HospitalDuring the lockdown period when children were not mixing, they were not transmitting viruses to each other. They were not building up immunity to the common infections they would normally encounter. When the restrictions were lifted, children began to mix, viruses began to circulate freely - and they suddenly were exposed with this lack of prior immunity to a whole battery of new infections.Prof Emma Thomson, University of GlasgowLarger studies are urgently needed to investigate the role of AAV2 in paediatric hepatitis cases.We also need to understand more about seasonal circulation of AAV2, a virus that is not routinely monitored,it may be that a peak of adenovirus infection has coincided with a peak in AAV2 exposure, leading to an unusual manifestation of hepatitis in susceptible young childrenClass II HLA-DRB1*04:01 alleleIdentified in 8/9 cases (89%)(background frequency of 15.6% in Scottish blood donors)Adeno-associated virus 2 (AAV2) mutationsMay be significant9 capsid gene mutations over-represented in these casesaltered phenotype, including substantial evasion of neutralising antibodies directed against wild-type AAV2,enhanced production yields, increased virion stability. Learn more about your ad choices. Visit megaphone.fm/adchoices Learn more about your ad choices. Visit megaphone.fm/adchoices
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Excess deaths AND long-term sickness dramatically increased in the UK
BA.5, immune escapeUploaded 30-06-22Vaccines and previous infections are protective against severe diseasePercentages of positives that were infected more than 90 days agoProgressively increasingNow, 12 % reinfections3 months ago, 8% reinfections6 months ago, 5% reinfectionshttps://www.youtube.com/watch?v=TwQp3Yc82akR = 1.1Up 27% on the weekUK, 1 in 21Scotland 1 in 15, highest ever ratesYoung people and young adults highestWill go up for a time, summer mixing, festivalsConsistent with ONS datahttps://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/articles/coronaviruscovid19/latestinsightsOne week aheadHospital admissions up 37%List of covid symptomsRunny nose, 66%Sore throat, 65%Headache, 64%Persistent cough, 63%Fatigue, 62%Sneezing, 53%Hoarse, 44%Joint pains, 35%Fever, 31%Chills or shivers, 30%Muscle pains 29%Dizzy, 27%Brain fog, 24%Sore eyes, 22%Altered smell, 21%Lower back pain, 22%Swollen glands, 19%Skipped meals, 17%Chest pain, 15%BA.5 is milder than previous variantsStill time off workHospital admissions due to large numbersOfficial data UKhttps://coronavirus.data.gov.ukCoronavirus vaccines should be updated for fallhttps://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-june-14-15-2022-meeting-announcementFDA advisory committeeDeadline, vaccine formula for October, nowBA.1 vaccine, in human tests for monthsArnold Monto, FDA advisory committeeWe’re being asked, more or less, to have a crystal ball todayNew multi-strain vaccine, original and omicronSome wanted BA.4 and BA.5, others BA.1Moderna, Novavax, Pfizer, each presented data to support their strategyModerna, bivalent, for example, original version + BA.1 variantPfizer BioNTech, only BA.1Pfizer presented mouse data on BA.4 and BA.5Novavax’s vaccine (not yet authorized in United States), additional doses of its existing vaccine could be protective? will these new formulations apply to children without testing? local or globalLyme disease Learn more about your ad choices. Visit megaphone.fm/adchoices Learn more about your ad choices. Visit megaphone.fm/adchoices
Green book, JCVI advises that breastfeeding women should be offered any suitable COVID-19 vaccine.Uploaded 02-09-22https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1098808/Greenbook-chapter-14A-17August2022.pdf(Updated, 17th August, 2022)Summary of the Public Assessment Report. For covid-19 vaccine, Pfizer/BioNTechttps://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-vaccine-for-covid-19/summary-public-assessment-report-for-pfizerbiontech-covid-19-vaccineWomen who are breastfeeding should also not be vaccinated. (Updated, 16th August, 2022)Summary of the Public Assessment ReportAuthorisation for Temporary Supply, COVID-19 mRNA Vaccine BNT162b2 (BNT162b2 RNA) concentrate for solution for injectionDepartment of Health and Social Care (DHSC), Pfizer Limited and BioNTech Manufacturing, GmbHhttps://www.gov.uk/government/publications/regulatory-approval-of-pfizer-biontech-vaccine-for-covid-19/summary-public-assessment-report-for-pfizerbiontech-covid-19-vaccineUpdated, 16th August, 2022Reproductive and developmental toxicityFertility and early embryonic development and embryofoetal developmentA combined fertility and developmental study (including teratogenicity and postnatal investigations) in rats is ongoing.Prenatal and postnatal development, including maternal functionNo such studies have been done.Studies in which the offspring (juvenile animals) are dosed and/or further evaluatedNo such studies have been done.Local toleranceNo such studies have been done. The assessments made as part of the general toxicity study should suffice and a separate study is not needed.Other toxicity studiesNo such studies have been done.Toxicity conclusionsThe absence of reproductive toxicity data is a reflection of the speed of development to first identify and select COVID-19 mRNA Vaccine BNT162b2 for clinical testing and its rapid development to meet the ongoing urgent health need. In principle, a decision on licensing a vaccine could be taken in these circumstances without data from reproductive toxicity studies animals, but there are studies ongoing and these will be provided when available. In the context of supply under Regulation 174, it is considered that sufficient reassurance of safe use of the vaccine in pregnant women cannot be provided at the present time: however, use in women of childbearing potential could be supported,provided healthcare professionals are advised to rule out known or suspected pregnancy prior to vaccination. Women who are breastfeeding should also not be vaccinated. Green book, updated 17th August 2022Specific population groups https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1098808/Greenbook-chapter-14A-17August2022.pdfPregnancy There is no known risk associated with giving inactivated, recombinant viral or bacterial vaccines or toxoids during pregnancy or whilst breastfeeding (Kroger et al, 2013). Developmental and reproductivity testing of the Pfizer BioNTech, Moderna and AstraZeneca vaccines in animals have not raised any concerns. JCVI has therefore advised that women who are pregnant should be recommended to receive primary immunisation, and that pregnancy is considered a clinical risk group for the autumn booster programme. Routine questioning about last menstrual period and/or pregnancy testing is not required before offering the vaccine. Surveillance of the inadvertent administration of COVID-19 vaccines in early pregnancy is being conducted for the UK by the UK Health Security Agency Immunisation and Vaccine Preventable Diseases Division, to whom such cases should be reported.1 This surveillance is being undertaken to document safety in women who unknowingly receive a vaccine in early pregnancyBreas Learn more about your ad choices. Visit megaphone.fm/adchoices
Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2 Uploaded 07-08-21https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00198-X/fulltextPDFhttps://www.thelancet.com/action/showPdf?pii=S2352-4642%2821%2900198-Xhttps://www.bbc.co.uk/news/health-58071898BackgroundInfection is usually asymptomatic or causes a mild illness of short durationPersistent illness has been reportedTo determine illness duration and characteristics in symptomatic UK school-aged childrenCOVID Symptom StudyMethodsProspective cohort studyAged children 5–17 yearsReported by an adult proxyIllness duration and symptom prevalence, for children testing positiveData from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessedFindings, Children aged 5–17 March 24, 2020 to Feb 22, 2021N = 258,790 Valid test result, n = 75,529 had valid test results for SARS-CoV-2.Positive test result, n = 1,734 children(588 younger and 1,146 older children)And had a calculable illness durationThe most common symptomsHeadache 1,079 (62·2%) of 1734 childrenFatigue 954 (55·0%) of 1734 children)Median illness duration Children testing positive, 6 days Children testing negative, 3 days Illness duration associated with age(Spearman's rank-order rs 0·19, p less than 0·0001)Median illness duration was longer for older childrenOlder children, 12 to 17 years, 7 daysYounger children, 5 to 11 years, 5 daysIllness duration of at least 28 days77 (4·4%) of 1,734 children59 (5·1%) of 1,146 older children18 (3·1%) of 588 younger children(p=0·046)After day 28, median 2 symptomsFirst week of illness, median 6 symptomsCommonest symptoms, first 4 weeks of illnessFatigue 65 (84·4%) of 77Headache 60 (77·9%) of 77Anosmia 60 (77·9%) of 77Symptoms for at least 5625 (1·8%) of 1379 childrenInterpretationCOVID-19 in children is usually of short duration with low symptom burdenSome children with COVID-19 experience prolonged illness durationSymptom burden did not increase with timeMost recovered by day 56 Learn more about your ad choices. Visit megaphone.fm/adchoices Learn more about your ad choices. Visit megaphone.fm/adchoices
Post-Vaccination Syndrome: Uploaded 19-11-23A Descriptive Analysis of Reported Symptoms and Patient Experiences After Covid-19 Immunization https://www.medrxiv.org/content/10.1101/2023.11.09.23298266v1.full.pdfYale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) Study (online)https://medicine.yale.edu/ycci/listen-study/LISTEN study, approved by Yale University Institutional Review BoardIntroductionA chronic post-vaccination syndrome (PVS) after covid-19 vaccination has been reported but has yet to be well characterized.A chronic syndrome with symptoms that begin soon after vaccinationMethodsPeople who joined, May 2022 to July 2023N = 241 individuals, (211 from the US)aged 18 and older,who self-reported PVS after covid-19 vaccination,Deep immune profiling is used for some individualsResultsMedian age of participants, 46 yearsAmong participants with PVS127 (55%) had received BNT162b2 [Pfizer-BioNTech]86 (37%) received the mRNA-1273 [Moderna]Time from index vaccination to symptom onsetMedian time, 3 days (IQR: 1 day to 8 days). Time from vaccination to symptom survey completion595 days (IQR: 417 to 661 days)Median Euro-QoL visual analogue scale score was 50 (IQR: 39 to 70). The five most common symptomsExercise intolerance (71%)Excessive fatigue (69%)Numbness (63%)Brain fog (63%)Neuropathy (63%)In the week before survey completion(Experienced at least once in the week)Feeling unease (93%)Fearfulness (82%)Overwhelmed by worries (81%)Feelings of helplessness (80%)Anxiety (76%)Depression (76%)Hopelessness (72%)Worthlessness (49%)Concerns related to living situations and food security were also prominent. Symptom Severity When asked to quantify symptom severity on their worst days,(0 representing a trivial illness and 100 unbearable condition)Participants reported a median severity of 80Interventions to treat their conditionParticipants reported a median of 20 (IQR: 13 to 30). Oral steroids, 116 (48% participants)Gabapentin, 61 (25%)Low-dose naltrexone, 48 (20%)I, 44 (18%)Propranolol, 27 (11%)Bronchodilators, 26 (11%)More than 500 additional treatments were reported by participantsLimiting exercise or exertionQuitting alcohol or caffeineHydration and increasing salt intakeIntermittent fasting ConclusionsIn this study, individuals who reported PVS after covid-19 vaccination had low health status, high symptom burden, and high psychosocial stress,despite trying many treatments. There is a need for continued investigation to understand and treat this condition. Looks like you can join, Kindred studyKindred is a community of patients, working with researchers to power more useful, impactful progress.https://www.kindred.hugo.health/research/listen-studyhttps://kindredapp.hugo.health/auth/login?ref=%2F Learn more about your ad choices. Visit megaphone.fm/adchoices Learn more about your ad choices. Visit megaphone.fm/adchoices