COVID-19 Causes Liver Inflammation in Children

Medical News: Immune Cells Unmasked as Culprits in Child Hepatitis Cases
A groundbreaking new study has uncovered a possible link between unexplained severe hepatitis in children and past COVID-19 infections, suggesting the liver inflammation could be a hidden post-COVID condition. The research, conducted by an international team from University Medical Center Freiburg (Germany), Medical University of Innsbruck (Austria), Ludwig Maximilian University Munich (Germany), Istanbul University (Turkey), Medical University of Vienna (Austria), and the University of Lisbon (Portugal), used cutting-edge imaging technology to investigate liver samples from affected children.


COVID-19 Causes Liver Inflammation in Children

Doctors and researchers were puzzled in 2022 when a spike in acute hepatitis cases emerged in children across the United Kingdom and other countries, with no obvious cause such as the hepatitis A to E viruses. Some children became so ill that liver transplants were required. This Medical News report explores a new scientific investigation that goes beyond previous theories involving adenovirus or adeno-associated virus 2 (AAV2), shining a spotlight instead on the potential role of SARS-CoV-2, the virus responsible for COVID-19.
 
COVID-19 Infection Detected in the Liver
The study involved 12 children diagnosed with acute hepatitis of unknown origin. Most of them had previously tested negative for active SARS-CoV-2 infection, yet deeper tissue analysis revealed something far more compelling. Researchers discovered traces of SARS-CoV-2 antigens still lingering in liver tissue - specifically in ACE2-expressing cells, which are known to be viral entry points.
 
Strikingly, 11 out of the 12 liver biopsies showed clear presence of these viral remnants, even though standard PCR tests at the time of admission had shown no signs of an ongoing infection. This evidence strongly points to SARS-CoV-2 as a persistent factor triggering immune-mediated liver damage in children, weeks or even months after their apparent recovery from COVID-19.
 
A Hostile Immune Reaction from Within
Using advanced spatial single-cell imaging techniques, the team mapped out how immune cells behaved in the liver tissue. They observed intense immune activity, particularly involving CD8+ T cells - also known as killer T cells - which are usually deployed by the body to attack infected or abnormal cells. These T cells appeared to be aggressively attacking liver cells in the areas where SARS-CoV-2 antigens were still present.
 
A trio of immune cell interactions stood out: CD8+ T cells, myeloid cells, and specialized blood vessel cells called CX3CR1+ endothelial cells were found working together in microenvironments that correlated with the most severe liver damage. This immune attack pattern appeared to be orchestrated and localized - pointing to an immune system gone awry, likely in response to leftover viral antigens.
 
Peripheral Blood Also Shows Signs of Immune Activation< ;br /> Further analysis showed that these inflammatory processes were not limited to the liver alone. In a subset of children, researchers found signs of highly activated CD8+ T cells in the blood as well. These cells expressed markers like PD-1 and CD38, which are often associated with chronic activation and immune exhaustion - a hallmark of post-viral syndromes.
 
Steroids May Be Key to Recovery
The good news is that despite the severity of the liver inflammation, none of the children in the study required a liver transplant. Instead, 10 of the 12 children responded well to corticosteroid therapy, which helped suppress the harmful immune response. However, two children experienced a relapse after tapering off the steroids, indicating that careful long-term management is necessary.
 
Why This Matters for the Future
The findings highlight that COVID-19 can leave behind more than just a cough or fatigue. It may quietly continue to affect organs like the liver long after the initial infection has cleared. This is especially troubling for children, a group previously thought to be at lower risk for severe COVID complications. It also challenges earlier ideas that blamed adenoviruses as the main cause of the hepatitis outbreak.
 
These new insights suggest that routine COVID-19 testing and antigen screening should be included in the diagnostic workup for children presenting with unexplained hepatitis. Furthermore, the presence of viral antigens in immune-infiltrated zones supports the theory that persistent viral reservoirs could be triggering these immune flare-ups.
 
Conclusions
This study provides compelling evidence that acute hepatitis of unknown origin in children could represent a post-acute sequela of COVID-19, driven by lingering viral antigens that provoke a targeted immune response in the liver. The aggressive behavior of CD8+ T cells, the role of endothelial and myeloid cells, and the effectiveness of corticosteroids all point to an immune-mediated mechanism likely initiated by prior SARS-CoV-2 exposure. Continued monitoring and better understanding of long-term viral effects in children are urgently needed. These revelations also call for heightened vigilance among pediatricians when treating unexplained liver inflammation in the post-COVID era.
 
The study findings were published in the peer reviewed journal: Gut
https://gut.bmj.com/content/early/2025/04/05/gutjnl-2024-333880
 
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