What if Covid had something to do with it? A wave of cases of acute hepatitis in children worries health authorities. In a few weeks, at least 450 cases have been documented worldwide, of which 31 required liver transplantation and 11 died. The cause of this hepatitis, which mainly affects children under the age of five, is still unknown. The most likely suspect at the moment is adenovirus AD-41, known to cause gastroenteritis-like diseases in children, as it was traceable in the blood of most children who developed this hepatitis. But this trace is not yet very solid: primarily because this adenovirus usually does not affect the liver; also because it was not found in liver biopsies taken from these patients, suggesting that this organ was not directly infected with this virus. Another hypothesis being investigated is that of SARS-CoV-2 coronavirus, which is responsible for Covid-19. Hypothesis supported by recent studies suggesting that coronavirus would play an important role in the triggering of these hepatitis.
Covid in children may affect liver function
Several studies have already shown that Covid-19 can cause an increase in the concentration of several liver enzymes in the blood, especially alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as observed during a hepatitis. This observation has just been confirmed in children by researchers at Case Western Reserve University (Cleveland, USA) in a pre-print published online on May 14, 2022 (not yet peer review).
They compared a cohort of 245,000 children with Covid with a cohort of 550,000 children with other respiratory infections. After checking for several risk factors, such as age, weight and ethnicity, they found that the risk of liver damage was higher in Covid patients with abnormally high levels of these enzymes (ALT and AST) as well as bilirubin, a pigment that accumulates during hepatitis and causing jaundice (or jaundice). This increased risk was present for up to six months after infection, as the authors say, “suggests acute and prolonged hepatic consequences in pediatric Covid-19 patients “.
This liver effect can be severe
However, this liver damage in covid patients is usually insignificant, except in patients who already have a liver disease. But a study published in May in Journal of Pediatric Gastroenterology and Nutrition showed that these disorders can be severe even in patients without any particular history of liver disease. Doctors at the Children’s Hospital in Cincinnati (USA) have listed the case of a 3-year-old patient who developed autoimmune hepatitis after having a mild form of Covid.
This child, who was in good health before the infection, was hospitalized three weeks after Covid with fatigue and jaundice.
What if Covid had something to do with it? A wave of cases of acute hepatitis in children worries health authorities. In a few weeks, at least 450 cases have been documented worldwide, of which 31 required liver transplantation and 11 died. The cause of this hepatitis, which mainly affects children under the age of five, is still unknown. The most likely suspect at the moment is adenovirus AD-41, known to cause gastroenteritis-like diseases in children, as it was traceable in the blood of most children who developed this hepatitis. But this trace is not yet very solid: primarily because this adenovirus usually does not affect the liver; also because it was not found in liver biopsies taken from these patients, suggesting that this organ was not directly infected with this virus. Another hypothesis being investigated is that of SARS-CoV-2 coronavirus, which is responsible for Covid-19. Hypothesis supported by recent studies suggesting that coronavirus would play an important role in the triggering of these hepatitis.
Covid in children may affect liver function
Several studies have already shown that Covid-19 can cause an increase in the concentration of several liver enzymes in the blood, especially alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as observed during a hepatitis. This observation has just been confirmed in children by researchers at Case Western Reserve University (Cleveland, USA) in a pre-print published online on May 14, 2022 (not yet peer review).
They compared a cohort of 245,000 children with Covid with a cohort of 550,000 children with other respiratory infections. After checking for several risk factors, such as age, weight and ethnicity, they found that the risk of liver damage was higher in Covid patients with abnormally high levels of these enzymes (ALT and AST) as well as bilirubin, a pigment that accumulates during hepatitis and causing jaundice (or jaundice). This increased risk was present for up to six months after infection, as the authors say, “suggests acute and prolonged hepatic consequences in pediatric Covid-19 patients “.
This liver effect can be severe
However, this liver damage in covid patients is usually insignificant, except in patients who already have a liver disease. But a study published in May in Journal of Pediatric Gastroenterology and Nutrition showed that these disorders can be severe even in patients without any particular history of liver disease. Doctors at the Children’s Hospital in Cincinnati (USA) have listed the case of a 3-year-old patient who developed autoimmune hepatitis after having a mild form of Covid.
This child, who was in good health before the infection, was hospitalized three weeks after Covid with fatigue and jaundice. Laboratory studies showed very high levels of ALT, AST and bilirubin, and liver biopsy showed inflammation of the liver. There was also a high level of autoantibodies directed against the liver, suggesting an autoimmune form of hepatitis. On the other hand, there was no increase in the markers characteristic of pediatric inflammatory syndrome (PIMS), indicating that this acute hepatitis was not due to this post-Covid syndrome. The patient was cured thanks to anti-inflammatory (corticoid) and immunosuppressive (azathioprine) treatments. However, the authors specify that it is impossible to prove that coronavirus was the direct cause of this hepatitis, even though it seems likely.
The presence of coronavirus in these patients may be underestimated
Coronavirus may therefore be involved in these cases of acute hepatitis in children. However, this trace has not yet been favored by the authorities, primarily because coronavirus has not been detected in a large proportion of patients with this disease. “It is possible that children have reservoirs of coronavirus in the gut and other tissues from a previous infection, but that coronavirus can no longer be detected by PCR testing.”, Answers Petter Brodin, professor of pediatric immunology at Imperial College London.
This is actually what was observed in an Indian study, published online in preprint on May 9, 2022. These authors present the cases of 47 children who developed hepatitis after coronavirus infection between April and July 2021, during the wave caused mainly by Delta variants. This hepatitis was associated with a PIMS for ten of these patients, against 37, for whom the liver was the only affected organ. And while the majority of these patients had negative PCR tests for coronavirus (35/37), they all had antibodies to coronavirus in their blood, suggesting previous infection.
Coronavirus can set the stage for adenovirus
However, the coronavirus has infected millions of children around the world for two years, and yet these cases of acute hepatitis remain rare. “This may be because it requires a combination of several conditions such as genetic predisposition, a reservoir of SARS-CoV-2 in the intestines and another infection with a specific strain of adenovirus for a limited period of time.”Launches Petter Brodin, who proposed a hypothesis that could explain the implication of coronavirus in these cases of hepatitis in a letter published in The Lancet Gastroenterology and Hepatology May 13, 2022
He reminds us that coronavirus can remain for a long time in children’s digestive system, which can lead to a repeated release of viral proteins, which can activate the immune response. That part of the virus’ Spike protein is also very similar to staphylococcal enterotoxin B, which triggers a significant activation of T lymphocytes (killer cells that are essential in the immune response), which can cause an inflammatory condition. And he suggests that this inflammation may be exacerbated by AD-41 adenovirus.
“The spike protein in SARS-CoV-2 could act as a superantigen, that is, a molecule that can activate T lymphocytes in a non-specific way and thus cause inflammation. And we know that these superantigens can be amplified by adenovirus infections, explains Petter Brodin. In mice, an adenovirus infection accompanied by the presence of the staphylococcal superantigen leads to hepatitis, whereas adenovirus allyou alone or the antigen alone does not cause this disease“These cases of acute hepatitis would therefore not be caused by infection with adenovirus or coronavirus in isolation, but by an immune response out of control after a double infection. A hypothesis that needs to be proven but which can confirm the involvement of Coronavirus in these cases of hepatitis in children.