Could SARS-CoV-2 infection result in serious clinical manifestations in children, close to the symptoms observed in Kawasaki disease ? At the end of April, pediatric services in the United Kingdom, France and the United States reported a small number of cases of children hospitalized with a systemic inflammatory disease, the symptoms of which evoke this rare inflammatory disease. In the current epidemic context, the emergence of these clinical signs and their link with Covid-19 raise questions.
What is Kawasaki disease?
Rare, this acute illness is characterized by an inflammation of the wall of blood vessels, particularly those of the heart (coronary arteries). It mainly affects young children before the age of 5. Although cases have been reported worldwide, the disease is more common in Asian populations. In Europe, 9 out of 100,000 children report the disease each year, with an annual seasonal peak in winter and spring. Thanks to early immunoglobulin treatment, the vast majority of patients recover quickly and have no sequelae. In addition, they hardly ever redevelop the disease.
Its cause is still poorly understood, although it is now clear that Kawasaki disease is linked to the presence of certain viruses in the body. Its triggering has indeed been associated with several types of viral infections, and in particular with respiratory or enteric viruses . The disease observed in children who are affected by it is a consequence of the over-activation of the immune system following infection with one of these viruses. Genetic factors also play a major role in explaining the vulnerability of some children to the disease.
What can we say about the cases observed in recent days?
It should first be emphasized that, among the cases identified in French hospitals in recent days, the clinical manifestations are not quite the same in all children.
Three presentations stand out:
- children with the classic clinical signs of Kawasaki disease, the emergence of which may correspond to the annual peak. Some of these cases are associated with the detection of SARS-CoV-2 but other viruses may also be involved;
- of children with more atypical forms of Kawasaki disease and out of the usual age group (the median age being 8 years), with greater involvement of the heart (inflammation of the heart muscle) than in the form ” classic ”and intense biological inflammation reflecting a cytokine storm, as seen in severe forms of Covid-19 in adults
- children with immediate heart failure due to myocarditis (inflammatory damage to the myocardium, the muscle tissue of the heart), with little or no evidence of Kawasaki disease.
There is a strong coincidence between the onset of these cases and the Covid-19 pandemic, but not all patients tested positive. Several questions therefore remain unanswered and are currently the subject of further investigation in pediatric services.
It is known that SARS-CoV-2 has been implicated in lesions in the blood vessels reaching many organs: lungs, nervous system, kidneys and heart. The atypical forms of Kawasaki and severe myocarditis observed in some of the hospitalized children recall this mechanism, but this link has yet to be explored.
Another question: why have these forms not been described in studies carried out in China, the original focus of the pandemic, when the disease preferentially affects populations of Asian origin?
For the moment, all the hospitalized children respond favorably to the classic treatments of Kawasaki disease, with a positive evolution, but the cases requiring intensive care require in addition tonicardiac treatments (which stimulate the heart).
What are the next steps ?
Epidemiological monitoring and research on the subject must continue to understand how these cases fit into the current epidemic context. Only a tiny proportion were hospitalized with symptoms of Kawasaki disease. In general, children are at very low risk of developing serious forms of Covid-19. As in adults, the most severe forms occur in obese children.
Studies published in peer-reviewed scientific journals advance hypotheses as to why children are globally unaffected by Covid-19. They relate in particular to the absence of the ACE2 receptor, to which SARS-CoV-2 binds to infect human cells. This receptor is almost absent on the cells of the child, appearing with pulmonary maturation. These lines of research have yet to be confirmed in order to better understand the impact of the epidemic on young people.
Text produced with the support of Isabelle Kone-Paut, manager of the registry for Inserm’s Orphanet database and pediatrician at Bicêtre hospital (University hospitals Paris-Sud / AP-HP)