KAWASAKI – In a study published by a group of doctors from the Public Assistance-Hospitals of Paris (AP-HP), the new syndrome that strikes children, close to Kawasaki disease, turns out to be very serious, but also very rare and non-lethal if treated well …
[Mis à jour le 20 mai 2020 à 15h53] “Kawasaki pseudo-disease”, also known as “MIS-C” (for Multisystem inflammatory syndrome in children), which is on the rise in children in the wake of the coronavirus epidemic, continues to reveal its secrets to the medical world. A study on the subject has just been published by doctors from the Public Assistance-Hospitals of Paris (AP-HP). This study was conducted on 35 children with this multi-systemic syndrome, in other words resulting in an infection with multiple symptoms, ranging from digestive problems and diarrhea to respiratory and cardiac problems, passing by a high fever and skin rashes. A short text was published on Tuesday May 19 on the AP-HP website and more detailed conclusions in the specialized journal Circulation. In summary, this new study shows the effectiveness of immunoglobulin treatments for these particularly serious cases, but non-fatal if taken on time.
“Most of these children needed treatment to support impaired heart function and to be mechanically ventilated,” wrote the doctors, who said that ten out of 35 patients “were temporarily placed on circulatory assistance”. “This publication clearly shows that this rare complication of COVID-19 in children and exceptional in young adults can be very serious. The entire pediatric cardiology community agrees to identify a disease emergent which should be called multisystemic inflammation of the child associated with SARS-CoV-2 in which the attack of the cardiac muscle is in the foreground “, continue the authors. “The treatment, which can be superimposed on that of Kawasaki disease, seems to be effective in most children”, they conclude, affirming that all the children have been treated “with immunoglobulins sometimes associated with corticoids”.
Doctor Jimmy Mohamed of the AP-HP clarified on Europe 1 that these children “were on average ten years old” and “in a third of the cases, they presented comorbidities, such as overweight or asthma”. He calls on parents who notice digestive symptoms to consult their doctor, especially since the epidemic of gastroenteritis is over. “He can reassure you or refer you to a specialist,” he adds. While the coronavirus has been reputed to be underdeveloped and harmless to children since the start of the epidemic, this new infection is worrying around the world. Here are five key questions about this mysterious disease:
This multi-systemic inflammation in children (MIS-C) would be atypical and completely new. It would cause symptoms corresponding to some but not all known infections, which leads doctors to describe an “overlap” between a “normal” toxic shock and a typical Kawasaki syndrome.
- Kawasaki syndrome has been known since 1967 and its discovery in Japan. It is a mysterious blood vessel disease affecting the youngest, usually 1 to 8 years old, and characterized by “febrile vasculitis”, affecting the veins and small arteries. The cause of this vascular syndrome affecting young children remains unknown.
- The toxic shocks observed in children have several characteristics in common with the cytokine storm, a runaway of the immune system observed in the most severe cases of coronavirus and which leads to a hyper-inflammatory reaction which can become fatal.
The symptoms of MIS-C therefore borrow from one and the other and are also numerous: rashes, high fever around 39-40 °, lymph nodes, abdominal pain, vomiting or diarrhea, sometimes making you think of a appendicitis, but also respiratory and heart problems. Symptoms begin with digestive disorders and progress to a state of respiratory shock. Myocarditis, that is, inflammation of the muscle tissue of the heart, can follow and lead to heart failure. In summary, “the immune system reacts too strongly and creates damage,” says Véronique Hentgen, infectiologist and pediatrician in Le Parisien.
Dr. Liz Whittaker, of the faculty of medicine of the Imperial College of London, specialist in the infectious diseases, validates this thesis of an immune over-reaction. She released Thursday, May 13, more details on the symptoms of MIS-C. On Channel 4, she indicates that a significant proportion of sick children suffered from “acute abdominal pain and diarrhea”. Among them, “a very small group developed a shock to the heart”. “These children are getting very sick, their hands and feet are cold and they breathe very quickly,” she added, referring also to rashes, “red eyes and mouth” and fever. She assures that these children require urgent intensive care treatment. “Most children are very sick for four to five days, but their condition improves afterwards.”
The multiple infection known as “MIS-C” was the subject of an alert in France from April 27. Several doctors have since reported their observations to Santé publique France. During his press briefing on Tuesday May 19, 2020, the Director General of Health Jérôme Salomon, indicated that 152 cases had been listed since March 1, including 98 cases presenting “possible links with the coronavirus”. On Friday May 15, a press release from Public Health France calculated that the number of “reports of atypical pediatric systemic diseases” in the country was 144. In another statement, the health agency said that 67 cases (54%) involved girls. 72 young patients suffered from myocarditis, the most serious complication, 47 patients were spared (6 were awaiting classification). Resuscitation was required for 65 children and critical care unit for 25. The other children were hospitalized in the pediatric ward.
After a peak observed in week 17 (from April 20 to 26), the number of new cases reported has declined significantly since then, indicated Public Health France. According to other figures reported by Le Figaro Friday, May 15, 50% of affected children would have ended up in intensive care with severe inflammation. Most of the cases are concentrated in Île-de-France (72 cases, including 42 at the Necker hospital), but 12 have also been identified in the Grand-Est and 11 in the PACA region, “writes the daily.
The number of cases of this new infection quickly increased in France. A document sent on April 29 by the Rare Disease Center for Congenital Heart Defects first identified at least 25 cases in three weeks in the Paris intensive care unit, said BFMTV. In these patients aged mainly between 8 and 15 years, there were then about fifteen cases of myocarditis. Professor Pierre-Louis Léger, head of pediatric resuscitation at Trousseau Hospital (AP-HP) told the news channel at the end of April that he had counted three cases of this form of toxic shock in ten days at the hospital Trousseau, three or four at Robert Debré hospital and he estimated that the ten cases had been crossed at Necker, an assessment already “totally abnormal in this period”.
Professor Damien Bonnet, specialist in rare diseases at the Parisian hospital Necker-Enfants Malades, told the weekly Marianne on May 5 that Necker then had around 40 children concerned, even if not all of them were taken to intensive care. . “At Necker-Enfants Malades, there are approximately three children hospitalized per day for this new form of Kawasaki disease, admitted in intensive care areas, but not all in intensive care,” said the doctor. In a note on the coronavirus in children published the same day and relating to the reopening of schools, Public Health France specified that around forty cases were known in France, which suggests that the number of cases has then more than tripled in ten days.
The concern is first of all global. The British pediatric intensive care company (PICS) and the National Health Service (NHS), the British health authority, published on Monday April 27 a first alert which immediately concerned the European health authorities. Their communication was originally published in the Health Service Journal, intended for health professionals, to whom they asked to report the cases of “Kawasaki-like”, expressing their fear of a rapprochement with the Covid- 19. This type of internal alert in the medical network is common. But since then, the UK has reported a total of 100 cases, most of them affecting children between the ages of 5 and 16 and having no health concerns, as well as the suspected death of an 8-month-old baby. “This is something that concerns us,” assured British Health Minister Matt Hancock at the end of April on LBC radio. He is not the only one. “We are following this issue carefully,” a spokesman for the Swiss Federal Office of Health told AFP. Dozens of cases of MIS-C have also been reported in Spain, Belgium, or northern Italy, where the Covid-19 epidemic has taken its toll.
The new multi-symptom infection was also the subject of an alert by the American authorities this Thursday, May 14, intended for health professionals. Called multi-inflammatory syndrome in children (MIS-C) by the American Centers for Disease Prevention and Control, it already affects a hundred cases across the Atlantic and has already killed at least three children in the State of New York. The American authorities therefore call for vigilance and ask the doctors to report “any infant death with proof of an infection with SARS-CoV-2”. “Healthcare providers who have treated or treated patients under the age of 21 who meet the criteria for (disease) MIS-C should report suspected cases to their local health department,” said Prevention Centers Americans.
From France to WHO, authorities on alert
The World Health Organization (WHO) for its part spoke in early May “a few cases of children with this inflammatory syndrome”, but observed in a “really rare”. Reassuringly, the WHO recalled that “the vast majority of children with Covid-19 only have a slight infection and are recovering completely”. In a note published in mid-May (and available here), the organization nevertheless called on the health authorities to refer it to possible cases which would be noted in other countries. She announced that she has started a study to determine the link between this new infection and Covid-19.
The 152 cases listed also concern France. But all these cases are still presented as exceptions by the health authorities as well as by many doctors. Since his first intervention on the subject, on April 29 on France info, the Minister of Health Olivier Véran wants to reassure, mentioning “fairly rare diseases” and insisting above all on the state of alert of the health services on the question. “All the pediatric resuscitations in France are on alert to send back the reports that I follow day by day,” he said to the deputies on May 2. The death of a child in Marseille has not really changed the discourse: we are talking about a resurgence of “exceptional cases” that must be monitored closely, but not a new “epidemic”, as the said Damien Bonnet, head of service at the Rare Disease Center at Necker Hospital.
In France, out of the 152 cases identified, there is only one death at this stage from this multi-systemic infection. A 9-year-old boy died in Marseille on Saturday, May 9, 2020. The latter was part of a group of five children admitted to the Timone hospital for suspected Kawasaki syndrome, instead of the three generally reported annual cases, indicates Provence. Professor Fabrice Michel, head of the pediatric resuscitation service in Timone, said the child died after seven days of care in their services. He had been transported to hospital after “severe discomfort with cardiac arrest” at his home, located in Marseille. Timone doctors, as well as the AP-HM in a statement, gave further details on this dramatic case. The heart attack would indeed be “linked to this syndrome” called “post-Covid infection”. Serological analysis showed that the child had been “in contact” with the coronavirus, but had not developed the symptoms.
It remains to be determined whether the young victim presented “co-morbidities”. “It will be advisable to exploit his medical file, in order to understand if he did not have a preexisting pathology”, specifies Fabrice Michel, whereas Public Health France wrote for his part that he presented “a neuro-developmental comorbidity” . The father of the child meanwhile assured on BFMTV Monday, May 18, that his son was “in excellent health”. He considers that the drama “could have been avoided” and plans to file a complaint against the Timone hospital in Marseille. Presented to the emergency room for the first time, the child was, according to him, sent home, with a prescription and antibiotics for a suspicion of scarlet fever, before a serious worsening of his condition and his admission to the pediatric resuscitation service of the Timone May 2.
Another suspicious death in the UK intrigues European health authorities. An 8-month-old baby died last April at Derriford Hospital in Plymouth, possibly from this mysterious infection. The mother of the infant has just launched an appeal to the British authorities judging “insane” the fact that the children return to school on June 1 across the Channel. “Other children will die. Other parents will be in the same unimaginable situation unless the government begins to listen to the advice of scientists,” she told the Mirror.
For Professor Fabrice Michel de la Timone in Marseille, who was responsible for the first fatal case in France, on the contrary, we must continue to “reassure parents”. “All the other cases of which we are aware have recovered, within a few days, after treatment with immuglobulin”, he underlines to La Provence. “We talk a lot between us about this syndrome, because it takes very diverse forms, so we are very attentive”, but the cases listed “should not worry too much”, he assured, warning all the same parents to “consult when children have fever for more than two days and associated signs”. “What is certain is that this disease remains fortunately very rare. It can be serious but progresses in the majority of cases”, adds the AP-HM. “In case of high and lasting fever, inflammatory manifestations (lymph nodes, rashes) in children, it is advisable to seek medical advice quickly”, also recommended Public Health France on May 15.
Among the questions that arise regarding the multiplication of these cases, that of the category of children affected also emerges. According to the medical journal The Lancet, genetics could be decisive, the first cases observed in England being mainly “of Afro-Caribbean origin”. The African and Caribbean populations seem particularly exposed in France as well and it is in these populations that we would observe the most severe cases. The child dead in Marseilles was “of African origin” was content to indicate Pr Michel de La Timone, without extrapolating. While in France, ethnic statistics are prohibited, an exception could be made for health reasons. A request to the National Commission for Data Protection (Cnil) is being considered to better understand this infection.
The link between MIS-C and the coronavirus epidemic now appears to be established. In the recent AP-HP study, mentioned at the top of this article, almost 90% of the 35 children treated had a Covid-19 positive PCR or serology. “The link with infection with the SARS-CoV-2 coronavirus is proven in 88% of them who have developed antibodies against it”, writes the AP-HP on its website. The coronavirus is also suspected from the start, at least as a trigger for this infection that strikes some children.
Professor Alexandre Belot, pediatrician at the Mother-Child-Child Hospital in Lyon, who led an epidemiological study to identify all cases with Public Health France, told Parisians bluntly on May 15 that “the link between the virus and Kawasaki syndrome “was now” confirmed “. “We noted a notable increase in the number of cases four weeks after the epidemic wave which crossed the country, then a significant reduction. They were concentrated in the regions where the virus was strongly present: the Great East (9.6% cases), Ile-de-France (58.4%) and, to a lesser extent, Auvergne-Rhône-Alpes, “explains the scientist.
According to the press release from Public Health France dated May 14 and relating to 125 cases observed, 52% indeed displayed a PCR and / or serology positive for SARS-CoV-2. The link to the virus was “probable” in 15 other children analyzed (12%). For 29 patients (23%), the results were still pending and the status was unknown for the other 16. “These results are very much in favor of a link between infection with SARS-CoV-2 and this pathology”, concluded the press release, which also recalled that the young victim who died in Marseille also displayed a “positive” serology opposite the Covid-19.
The Francophone Society for Rheumatology and Inflammatory Diseases in Pediatrics (SOFREMIP) published a letter on April 29, still available on the website of the French Pediatric Society. Its experts said they were “challenged for several weeks by the description of pediatric cases in resuscitation of myocarditis with circulatory failure”. “In the current context of the COVID-19 pandemic, the association of these cases with SARS-CoV2 is possible, even if it could not be proven for all patients”, wrote the members who deemed “essential by Besides, don’t forget to look for other viruses which are classically associated with atypical Kawasaki disease and which could circulate during this season: adenovirus, enterovirus, coxsackie “.
70 to 75% of affected children have been “in contact” with the coronavirus
Among the various doctors, researchers and pediatricians interviewed, many have been highlighting for weeks the rather disturbing concomitance between these new infections and the SARS-CoV-2 epidemic. In Necker, Damien Bonnet estimates that usually, one observes a severe form of Kawasaki disease per month, while in three weeks, around twenty have been identified. A part or a “majority” of children struck by this new form on Kawasaki syndrome have tested positive for Covid-19 according to European data. “This is the case for more than half of them (70%). The other children have been in contact with someone infected with the coronavirus,” said Professor Bonnet recently in Marianne, who said that ” the likelihood of a link between the two is high. “
Asked for his part on BFMTV, Professor Ricardo Carbajal, head of pediatric emergencies at Trousseau hospital in Paris, assured that “75% of the cases” observed in these children had “proven family contact” with the coronavirus. “We conducted a very thorough survey of the families we contacted, to find out if these children had been in contact with proven patients during the confinement and we found for 75% of them, at least one contact occurred between 3 and 5 weeks before symptoms start. ” Professor Fabrice Michel de la Timone in Marseille, who reported the first death of a child due to MIS-C infection, the link with the coronavirus is also “difficult to deny”. Many Marseille patients have antibodies in their body, a sign of Covid-19 contamination.
A subsequent reaction to the coronavirus?
The fact remains that this influx of pediatric patients has lagged behind the coronavirus epidemic. According to the first hypotheses, multi-systemic disease could actually be a delayed collateral damage. “We do not claim that there is a causality between Covid-19 infection and these clinical pictures. But one hypothesis would make it a secondary disease of Covid-19, as a consequence of an infection that often went unnoticed. A delayed inflammatory phenomenon, “said Pierre-Louis Léger on BFMTV in early May.
The thesis of post-infectious disease, “with a secondary reaction to infection” is taken up by Damien Bonnet de Necker. According to him, the overwhelming immune system found in affected children could be a result of their contamination with coronavirus. Young patients may have first developed “good antibodies” to get rid of the coronavirus, before “a certain number of cells start to turn on excessively”. Infections could indeed be linked to the production of toxins in response to a bacterial infection.
In the Parisian Friday May 15, Professor Alexandre Belot put forward two hypotheses: “either the development of the disease is favored by an excess of the immune response of certain children, against a background of genetic factors. Either it is linked to mutations in the virus itself that would cause this type of response in young patients. “
“We have absolutely no medical explanation at this stage. Is this an inflammatory reaction that triggers a preexisting disease in children affected by this virus or another infectious disease? has a lot of questions, “said Minister of Health Olivier Véran at the end of April, taking up more or less the same assumptions. The minister said he did not have an answer at this stage and specified that “some affected children, but not all, have been found to be carriers of the coronavirus”. “I mobilize the healthcare community, the scientific community in France and abroad to have as much data as possible, to see if there is reason to make a link between the coronavirus and this form which, until now, n had not been observed anywhere, “he said.
A track also followed abroad
Abroad also, the track of a post-coronavirus reaction is followed, as indicated by the American pediatrician Sunil Sood, of the Cohen children’s medical center in New York, interviewed by AFP. “They had the virus, their body fought it. But now there is this delayed and excessive immune response,” according to this specialist. But as if to further thicken the fog that reigns over both the coronavirus and these new infections, AFP specifies that no similar case has been reported in children in Asia, including in China where the virus appeared in December. It is at this level that genetic factors and a possible mutation of the virus are evoked.
The very famous medical journal The Lancet for its part published this Thursday, May 13, 2020 an article making quite clearly the link between SARS-CoV-2 and MIS-C which strikes children. The study is based on the cases observed in Bergamo, one of the epicentres of Covid-19 in Italy. While the Lombard city hospital treats an average of one Kawazaki syndrome case per quarter, it listed ten between February 18 and April 20, 2020, thirty times more than usual. Researchers cited by The Lancet also said that eight of the ten children hospitalized had tested positive for the coronavirus.
If these mysterious infections are really a subsequent reaction to a coronavirus infection, should we fear an increase in cases with deconfinement? This is a likely scenario according to several researchers around the world. “The comparison of hospitalization curves for COVID-19 and for this pathology is in favor of an average time to onset of these systemic inflammatory diseases of 4 weeks after infection with SARS-CoV-2”, indicated Public Health France on May 14. A delay confirmed more or less by the American health authorities, who estimate that the appearance of these inflammatory symptoms seems to intervene “four to six weeks after the child has been infected with the virus, when he has already developed antibody, “wrote AFP.
In the UK, Dr. Liz Whittaker also confirms: “The syndrome begins at least three weeks after infection with the coronavirus, although the children affected have all been asymptomatic carriers”. She actually considers possible an increase in cases during or after deconfinement. “It’s a possibility,” she told Channel 4. Professor Russell Viner, president of the Royal College of Pediatrics and Child Health (RCPCH), also believes that “if this is a phenomenon post-infectious, we could see others, but the important thing is that it can be avoided. ” He therefore calls to inform parents to “make sure they can recognize the syndrome and ask for help early”.
In France, before the death of the first child affected by this multiple infection, the scenario of an explosion of cases with deconfinement and in particular the resumption of school was not on the agenda. It is very likely that this line will be maintained in the coming days. Alexandre Belot, of the Mother-Child-Child Hospital of Lyon, recalls in Le Parisien that “all learned societies of pediatrics have called for school resumption” and that “the recommendations in favor of a return to school do not not change “despite this new infection. “The situation is extremely rare. There are a few dozen cases of Kawasaki, against millions of people who have been exposed to the virus,” said the pediatrician, who recalls that children are significantly spared from Covid-19. “For hundreds of thousands of children, there has been no manifestation of the disease. The majority of them are asymptomatic and – as we now know – very few vectors of Covid-19,” he said. he. And to conclude: “There is a magnifying glass effect on the coronavirus but you should know that between January and March, ten children died from the flu”.