The current bout of unexplained hepatitis in Covid-hit children is related to the virus in some way

Dr Arvinder Soin talks to Kaunain Sheriff M about the recent scientific papers on unexplained hepatitis in children – and says that it may be linked to Covid-19. He explains how the immune system activated Covid-19 and the antigen hanging around in the gut after recovery can trigger a large immune response. He suggests a three-month follow-up for every child who has been infected or exposed to infection in the family as a preventive measure.
Why? Dr Arvinder Singh Soin is one of the country’s top liver transplant surgeons. He is the Chief Hepatobiliary and Liver Transplant Surgeon and Chairman of the Institute of Liver Transplantation and Regenerative Medicine, Medanta. He has been closely studying Covid-19 and its impact on the liver and has been part of the team that has issued national guidelines on liver transplantation during the pandemic

Several countries are reporting severe hepatitis in children who have contracted Covid-19. A study from Madhya Pradesh, which is yet to be peer-reviewed, has shown that eight per cent of children in the group being investigated reported a unique form of hepatitis and subsequent asymptomatic Covid-19 infection. Can we say there is a link between Covid-19 and hepatitis in children?
In the West, there have been some cases of hepatitis, which are unexplained previously known causes. And there have been publications that have been peer-reviewed, including the one published in The Lancet last week, where they have talked about several children reporting unexplained hepatitis, where every parameter they test, usually, is found negative. The majority of them actually get well. But there has been a small number of cases, where children have actually developed severe liver cases that need a transplant. That is obviously of concern.
The timing suggests it is related to Covid. Because the chronology is suggestive of Covid having a role as such a condition wasn’t seen before the pandemic, the theory of a link between the two is gaining ground. I am specifically talking about the Lancet paper. I am aware of the non-peer-reviewed data from Madhya Pradesh, where they found 37 cases of hepatitis out of 457 patients of Covid-19.
The Lancet study detected adenovirus in nearly 80 per cent of the cases. Normally, this virus is fairly harmless. It causes gastritis, diarrhoea and vomiting but so far has not caused any severe illness. But now nearly 80 per cent of children with hepatitis have this virus. It is still not known if it is causally related. Researchers even analysed the type of adenovirus and found a particular strain called 41F in all samples. Now this strain is typically associated with mild gastro-intestinal illness in children. So, the theory going around is that somehow the immune system of children affected Covid-19 have developed abnormalities or been compromised to such an extent that the adenovirus, which is normally harmless, has manifested itself severely.

The same paper quoted studies in Israel, where most children with hepatitis had recovered from Covid-19; in the US, 70 per cent of kids had Covid-19 infection and in the UK, only 20 per cent had previous Covid-19 infection. So, the picture is not entirely clear. And the Indian data, of course, did not even look at it like that; it studied Covid-19 cases and found 37 children suffering from hepatitis. It is all a little blurry right now.
But as an expert in liver disease for over 30 years and as someone who does liver transplants in children literally every other day, I think it (the recent cases of hepatitis) is related to Covid pandemic in some way. I think it is very likely, in my view, that there is hepatitis which is previously not been seen that has come about in children because of Covid pandemic. Whether the pandemic prevented the exposure to usual antigens or bugs or whether the virus itself in a silent or infected form created the imbalance in the immune system needs to be looked into. But there has been some durbance in the children’s immune systems.
Another complication in children is the multi-system inflammatory syndrome, which has been documented all over the world. That is also a kind of immune reaction to previous Covid-19 infection, typically seen three to four weeks after recovery. The majority of the kids settle down with medical treatment. In our specialised children’s unit, we have not had a single mortality and we have seen over 200 cases of MISC. We had four hepatitis cases too but they were mild to moderate.
Currently, the scientific hypothesis is that the mystery hepatitis among children has been triggered an immune response caused Covid-19. Could you explain this?
Covid-19 activates the immune system in the patient. Whether you are symptomatic or not, have a mild or moderate version of the infection or not, you have some antigens. These are like genetic identities of the Covid-19 virus sitting in your gut. Over time, they will get absorbed and stimulate the immune cells, little little, even long after the infection is gone.
It is like inciting the enemy during a ceasefire. So, even the slightest skirmish on the border will activate the enemy in a big way. With the immune system activated the viruses and the antigen hanging around in the gut after recovery from Covid, even a minor infection caused the adenovirus or a repeat infection of Covid can trigger a large immune response. And when a large immune response happens, the patient can get hepatitis.

Children with Covid-19 have been mostly asymptomatic. Looking at this data, can we say that children are at a significantly increased risk of liver dysfunction after recovery?
It would be fair to say there is a risk of liver dysfunction after you recover from Covid-19. But the proportion of children or patients who get it is not large. It would be somewhere between the 10 and 20 per cent mark. But then that translates to a significant number. In all the seroprevalence studies that have been done in India, 60-70 per cent of children have been found to have Covid-19 antibodies. So, if you are surmising that 70 per cent of kids have developed infection and antibodies, then they are susceptible to this kind of hepatitis. That’s still a large number.
Given the limited knowledge on the long-term impact of Covid-19 on the liver, what are the preventive measures that need to be followed?
There are two things that you can do. First, prevent kids from getting Covid-19. That is easier said than done. We know that even without vaccination in India, 70 per cent of them had antibodies. Second, boost immunity with nutritious food, adequate sleep and intake of vitamin and mineral supplements whenever needed.
I would say that families that have had Covid-19 infection in their homes are very likely to have children who will be at risk of developing hepatitis. They should see a paediatrician and make sure that nutritious food and supplements, if necessary, are given.
How can parents identify these cases early? And when does one need to visit the special?
Like I said, if a kid is known to have Covid-19 in the past, he/she should follow up with a paediatrician for at least three months after recovery. Even if the parent has had Covid-19, it is likely that the child has been exposed. This is true for children younger than eight years because it is very difficult to contain them.