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Children at higher risk of infections, autoimmune diseases as M'sia returns to pre-Covid-19 normalcy

KUALA LUMPUR: Two years of Covid-19 restrictions have left children, especially those aged five and younger vulnerable to infections and at greater risk of developing allergies, asthma, hypersensitivities and autoimmune diseases, an expert warned.

Molecular virologist Dr Vinod Balasubramaniam believes this is partly due to reduced interactions with people and nature as a result of lockdowns and physical distancing, which have weakened their immune systems.

As young children enter or re-enter society with the majority of the pandemic standard operating procedures (SOPs) including mask-wearing and physical distancing lifted, they are not able to build up resistance to common bugs or viral pathogens, leaving them susceptible to infections and diseases, he said.

Consequently, he said the rise in multifaceted infections among children is expected now, but these should be treated with caution, especially if they exhibit severe symptoms.

Dr Vinod of the Jeffrey Cheah School of Medicine and Health Sciences at Monash University Malaysia said this when commenting on the recent surge in hand, foot, and mouth disease (HFMD), sudden emergence of hepatitis, and detection of Kawasaki Disease (KD) in children.

"Our immune system works exactly like our brain. It learns and develops over time and exposure to outer microbes is extremely important for it to collect 'data' and store it for future use.

"We have two main pillars in terms of immunity. We are born with an 'innate' immune system encoded in our genes, but this is 'tuned' by our 'adaptive' immune system, which collects data from the microbes around us to determine which are safe and which are dangerous.

"Without the right data, the immune system starts attacking things it shouldn't, causing allergies, asthma and autoimmune diseases (when the immune system targets your body's own tissues).

"The prolonged isolation due to Covid-19 lockdown in the previous years has definitely impacted the 'learning' process of our immune system, especially children," he told the New Straits Times.

Dr Vinod noted that the problem would likely be more prevalent in infants than toddlers.

Although the human immune system is largely mature by approximately age six, some key components are still developing into adolescence, he said.

As such, he said the only people who could be certain that the isolation policies would have no negative impact on their immune system's ability to self-regulate were adults.

Various studies, he said have posited that problems could arise when infants have limited microbial exposure.

For instance, he said it has been shown that children born by caesarean section were exposed to less of their mother's microbiota than others, they are also statistically more likely to suffer from allergies and inflammatory diseases.

Hand, foot, and mouth disease (HFMD)

Dr Vinod said now that the majority of the strict Covid-19 SOPs have been relaxed as countries head towards endemicity, there is a worldwide trend of surging infections in the children population, especially viral infections.

"Majority of the kids were under complete lockdown for the past couple of years and due to this, the number of cases of common viruses, for example, enteroviruses which cause HFMD infection were pretty much lower or non-existent.

"The children were not exposed to all these pathogens in the environment which they normally do in non-pandemic conditions, which has enabled them to build up their immune systems."

The Health Ministry had reported 22,463 HFMD cases nationwide until the 17th epidemiological week (April 24-30), of which, 96 per cent were children aged below six.

Health director-general Tan Sri Dr Noor Hisham Abdullah had on May 5 said the statistics marked a sharp spike of 12.8 times more compared to the same period last year, which saw only 1,752 cases.

Acute, severe hepatitis of unknown origin in children

Meanwhile, the recent series of unexplained cases of hepatitis in children around the world has also caused quite a stir.

In Malaysia, a four-year-old boy in Sabah was diagnosed with acute hepatitis in March where he underwent a liver transplant on March 30. Initial investigations found that he had contracted Covid-19 previously.

Dr Vinod pointed out that most of the reported cases worldwide were of acute hepatitis, which causes liver inflammation with symptoms like abdominal pain, diarrhoea and vomiting preceding presentation with severe acute hepatitis, and increased levels of liver enzymes and jaundice.

On April 23, the World Health Organisation (WHO) reported incidences of severe acute hepatitis of unknown origin among children aged between one month and 16 years old.

According to the Pan American Health Organisation's May 10 report, to date, 348 probable cases of severe acute hepatitis of unknown etiology have been reported in 21 countries, with 26 children requiring liver transplantation. Fifteen countries have reported five or fewer cases.

WHO had on May 11 said it was studying whether Covid has a role in the child hepatitis mystery.

Interestingly, Dr Vinod said a WHO report found that adenovirus has been detected in at least 74 of the cases worldwide and has been linked to be the causative agent of this outbreak.

Adenovirus is a family of viruses that commonly cause cold or flu-like symptoms, fever, sore throat, acute bronchitis, pneumonia, conjunctivitis, acute inflammation of the stomach, diarrhoea, vomiting, nausea and stomach pain.

It is known to spread from one person to another through close contact, coughing, sneezing and even by touching an object containing adenovirus and then further touching the mouth, nose or eyes.

However, the infection usually does not last long or become severe in kids unless they are immunocompromised, Dr Vinod said.

"In immunocompromised patients, adenoviruses can on rare occasions cause hepatitis. The sudden surge of the infection in kids is very rare, especially in children who don't appear to be immunocompromised."

If adenovirus is the cause of these cases, there could be a possibility that a newer variant of adenovirus has emerged that more easily causes hepatitis, he noted.

"Another angle of investigation worth looking at is whether co-infection with Covid-19 in these children with adenovirus has any role in inducing this acute condition."

"Further investigations are needed to confirm this and in the mean time parents and children should practice proper hygiene such as hand washing along with good respiratory hygiene and cough etiquette."

Kawasaki Disease (KD)

The majority of multi-system inflammatory syndrome (MIS-C) cases in children in Malaysia, which may present as KD is linked to Covid, prevalent in non-vaccinated kids, Dr Vinod said.

"The exact cause of MIS-C is not known yet, but it appears to be an excessive immune response related to Covid-19.

"Many children with MIS-C have a positive antibody test result. This means they have had a recent infection with the Covid-19 virus. Some may have a current infection with the virus."

Dr Vinod therefore said it is pertinent that children aged five to 12 and up to 17 are vaccinated immediately to prevent all the serious symptoms from Covid-19 including MIS-C.

He shared that patients with manifestations compatible with MIS-C were first identified in April 2020 during the height of the Covid-19 pandemic in the UK.

"Patients had hyperinflammatory shock with features similar to KD and toxic shock syndrome.

"Majority of patients with MIS-C presented with fever, signs of generalised inflammation, hypotension and shock, and multiple organ dysfunction."

Dr Vinod said most MIS-C cases were thought to occur after asymptomatic or mild Covid-19 infections, with an outsized inflammatory response coinciding with peak antibody production several weeks later. This, he said was seen in many paediatric patients, including in Malaysia.

Although the majority of the symptoms may look similar in children, both Covid-induced MIS-C and KD were not the same, he said.

"KD is an acute illness that affects mostly children six months to five years old—median age in the KD cohort was 25 months—and features inflammation of small and medium blood vessels.

"Although the cause of KD is unknown, it is believed to occur in genetically predisposed children after exposure to an environmental trigger such as an infection."

The Health Ministry in April posted an infographic on KD advising parents to seek immediate treatment if their child has symptoms to reduce the risk of heart complications.

KD, also known as Kawasaki syndrome was first detected by a Japanese paediatrician, Dr Tomisaku Kawasaki in 1967.

How can we protect pandemic children

Dr Vinod said it is imperative to keep up to date with children's vaccination schedule (National Immunisation Schedule) to limit the damage from these various infections.

"Not only do vaccines stop you from getting the infection that they are targeting, they also help with the training of the immune system in a nonspecific way, as we slowly ease into the new normal."

He further advised parents to allow children to play outside to boost their immunity.

"One question remains to be answered. Our innate and adaptive immune system will develop regardless of whether we are exposed to the microbial world or not. The question is, will they develop appropriately?

"The immune system of our kids lost two important years in their live in terms of 'learning'. These kids are at a higher risk of developing hypersensitivities and autoimmune diseases than anyone before them.

"The immune systems of children are not designed to develop in isolation from the microbial world, so let us consider letting children be children again albeit with caution especially completing the required vaccinations necessary for their immune system to continue learning."

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