Coronavirus disease (Covid-19) infection in children is often mild or asymptomatic, and rarely leads to death, but cases of an uncommon, but potentially fatal multisystem inflammatory syndrome in children (MIS-C) are being reported in India after being documented in Italy, Spain, the UK and the US.
MIS-C remains a rarity in India, where people under 20 accounted for just 1.22% of Covid-19 deaths as of August 22, according to data from the Union ministry of health and family welfare.MIS-C is marked by high fever, organ dysfunction and strongly elevated markers of inflammation, with many symptoms overlapping with those of the Kawasaki disease, another childhood ailment that leads to inflammation of the arteries (vasculitis), autoimmune dysfunction, encephalitis (swelling of the membranes surrounding the brain), cardiovascular shock and multiple-organ failure.
There is, however, a marked difference in inflammatory response and biomarkers associated with arterial damage in MIS-C and Kawasaki disease, according to a pre-proofcopy of a new study published in the journal Cell.A systems-level analysis of immune cells, cytokines and autoantibodies in healthy children, those with the Kawasaki disease before Covid-19, Sars-CoV-2 infected children, and children with MIS-C, showed that multiple autoantibodies were involved in triggering MIS-C, researchers from Italy and Sweden found.
Autoantibodies are immune proteins that mistakenly target a person’s own tissues or organs while cytokines are proteins that regulate immunity and inflammation.While fever, conjunctivitis, swelling in the foot, swollen lymph nodes (throat) and rash were observed in both diseases, headache, abdominal pain, vomiting, sore throat and cough were more common in MIS-C, the study found.This supports an earlier study published in The Journal of Clinical Investigation that found MIS-C is a post-viral hyper-inflammatory reaction to Sar-CoV-2, the virus that causs Covid-19, and was related to but distinct from Covid-19 and Kawasaki syndrome. The study found MIS-C was marked with elevated levels of two cytokines, IL-10 and TNF-α, which were not or minimally elevated in children with mild to severe Covid-19.
There were mild elevations of other cytokines and not IL-10 in Kawasaki disease.Two MIS-C case studies from the All India Institute of Medical Sciences, New Delhi, also demonstrated that while all children develop high fever, other symptoms vary widely. A two-and-a-half-year-old child with MIS-C developed ever, cough, runny nose and seizures while a six-year-old had fever and rash, but no seizure, cough or other respiratory symptoms.Differences in immune response, cross-reactive immunity to common cold coronaviruses, better health compared to the elderly, and differences in the expression of the viral entry receptor ACE2 that Sars-Cov-2 binds to infect human cells are among the factors that protect children from severe disease.
“Children have a strong innate immune response, which could be due to trained immunity because of frequent viral infections and vaccinations such as BCG. The expression of primary target receptors for Sars-Cov-2 varies with age, and that coupled with the excellent regeneration capacity of paediatric alveolar epithelium (respiratory membrane in the lungs) may lead to early recovery in children,” said Dr Rakesh Lodha, professor of paediatrics, AIIMS, New Delhi.
These findings are helping clinicians in Covid-19 management in children, who have limited treatment options as remdesvir is not approved for use in children under 12, and convalescent plasma is recommended once daily for two days.
“Treatment (can we explain} should be considered only after a risk-benefit analysis on a case-to-case basis after taking consent from parents. Tocilizumab may be considered in children with progressive disease with inflammation markers,” said Dr Lodha.
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