Benjamin Mateus
Global cases of acute hepatitis among children have grown sharply to 450 children across at least 20 countries since the outbreak was first brought to the attention of the World Health Organization (WHO) by the Scottish National Health Service in early April. Acute hepatitis is an inflammation of the liver that can lead to imminent liver failure, a life-threatening condition. At present, 12 children have died globally during the ongoing outbreak.
In their initial report to the WHO, the NHS Scotland wrote that “five children aged three to five presented to the Royal Hospital for Children, Glasgow with severe hepatitis of unknown etiology within a three-week period. The typical number of cases of hepatitis of unknown etiology across Scotland would be fewer than four per year.”
By April 8, the global case count had risen to 74. All cases had tested negative for the usually suspected viruses. A number of children were documented to have been infected with an adenovirus or COVID-19, though other factors were being considered.
On April 15, the WHO released the first of three disease outbreak alerts, asking health systems and public health officials to heighten their awareness and diligence in identifying, investigating and reporting hepatitis cases. They said, “Given the increase in cases reported over the past one month and enhanced case search activities, more cases are likely to be reported in the coming days.”
By April 21, 169 cases had been reported across 12 countries, ranging in age from one month to 16 years old. The bulk of these cases were from the United Kingdom, while the US had observed eleven cases by then. At this time, the WHO made clear that the COVID-19 vaccines were not implicated in the hepatitis outbreak, as a significant majority of the impacted children were unvaccinated.
On Tuesday, the WHO announced that the number of probable cases of hepatitis in children now stands at 348 spanning 20 countries across five global regions.
The recent spike in global pediatric hepatitis cases since late last month reflects additions made by the US Centers for Disease Control and Prevention (CDC) in their ongoing investigation. There are currently 109 such cases in the US from a total of 25 states and territories.
Dr. Jay Butler, the deputy director for infectious diseases at the CDC, noted that 90 percent of these children were hospitalized dating back to October 2021, when nine such cases were identified in Alabama. He said 14 percent required an emergent liver transplant and five of the children tragically died.
Dr. Philippa Easterbrook, a senior scientist at the WHO’s Global HIV, Hepatitis and STI Programmes, stated Tuesday, “At present the leading hypotheses remain those which involve adenovirus, but I think still there is the important consideration about the role of COVID as well, either as a co-infection or as a past infection. Over the last week, more testing has gone on… confirming that still around 70 percent of the cases that have been tested are positive for adenovirus.”
On Wednesday, the European CDC published an update indicating the total number of cases worldwide has reached 450. In the EU/European Economic Area, the total number of cases stands at 105, with Italy reporting the most cases at 35, followed by Spain with 22, then Sweden with 9. The United Kingdom currently has the most confirmed cases of any country at 163, and six countries have reported more than five cases.
On Thursday, Ireland reported the death of a child from acute hepatic failure, raising the global total to 12. Brazil is investigating another eight cases, bringing their total to 28. In all, the fatality rate is between 2-3 percent and rates of liver transplantation range between 10-15 percent.
The etiology for the devastating cases remains to be elucidated. The statement by Easterbrook is opaque, and many scientists have noted that the presence of adenovirus among cases does not directly implicate this ubiquitous virus as causative.
It seems more than coincidental that the sudden emergence of a rare disease never before described among healthy children has taken place just months after the massive wave of COVID-19 infections that spread across the globe during the Omicron BA.1 surge last winter. Seroprevalence studies indicate that potentially hundreds of millions of children have been infected worldwide since last December, making rare manifestation of COVID-19 infection more likely to arise.
Notably, acute hepatitis has been previously associated with multisystem inflammatory syndrome in children (MIS-C), which affects children after the acute phase of COVID-19 infection. In the US, the incidence of MIS-C has reportedly been around one in 3,000-4,000 COVID-19 cases.
In a tweet now shared more than 10,000 times, gastroenterologist Dr. Farid Jalali explained that adenoviruses have only caused acute liver failure in patients with severe immunodeficiency and not previously healthy children. The severity of the disease is dependent on the intensity and duration of the immunosuppression in cases where patients are being treated for malignancy on chemotherapy or taking anti-rejection medication after organ transplant.
Dr. Jalali explained that adenovirus infections are very common in children and can be detected in up to 11 percent of healthy, asymptomatic children from throat samples. Additionally, the virus can persist for months to years in approximately 30 percent of “immunocompetent” children.
He wrote, “Relying on adenovirus detection by PCR in children (often incidental due to persistence and shedding) can falsely attribute adenovirus as the cause of disease for which the clinician may have no other proper explanation (e.g., pediatric acute liver failure in context of COVID-19 pandemic?).”
Because of his expert and well-reasoned explanations and concerns, Dr. Jalali has received numerous threats and vilification by right-wing commentators.
Australian epidemiologist Dr. Raina MacIntyre weighed in on these issues with a rare but lengthy Twitter thread, noting, “It’s most likely a complication of COVID-19 but may take a while to be adjudicated as much.”
Dr. MacIntyre added, “Hepatitis is a known presentation of MIS-C and MIS-C is a late complication after the acute infection [of COVID]. So, the fact that [SARS-CoV-2] PCR is negative is not surprising… SARS-CoV-2 is tropic to the liver and commonly causes liver injury, so biological plausibility (one of the Bradford-Hill criteria for causation) is present.”
Interestingly, many of these children had not obtained COVID-19 antibody testing nor were the liver biopsies checked for SARS-CoV-2 virus.
Dr. MacIntyre asks pointedly, “And what about ideological reasons why there is a concerted effort to deny COVID as a cause and find another explanation? Any explanation? It’s called ‘escalating commitment to a failing proposition’ and is a normal reaction to accruing evidence that a vested position is wrong.”
The impact of COVID-19 on children has been repeatedly minimized by almost every world government. Last year, US President Joe Biden famously told a second-grader that she shouldn’t fear COVID-19, that schools are safe to return to and she was unlikely to infect her parents. These have proven to be bald-faced lies and COVID-19 is demonstrably dangerous for children, with tens of thousands of children having likely been killed by the virus worldwide.
Dr. MacIntyre concludes her thread by noting, “In the UK, children were denied vaccination for the longest time, and then belatedly and reluctantly offered it. When countries and experts have invested in this position, and evidence accrues that it is a wrong position, we see escalating commitment to a failing proposition… Perhaps this is why we have not seen a proper epidemiologic analysis of causation… yet. Yes, it may be caused by something else. But in the midst of the pandemic, COVID is the most likely cause.”
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