CDC alerts doctors to look for signs of mysterious coronavirus-related inflammatory disease in children

The advisory comes even as a study from Italy provides the first clear evidence of a link between Covid-19 and the inflammatory condition


                            CDC alerts doctors to look for signs of mysterious coronavirus-related inflammatory disease in children
(Getty Images)

The US Centers for Disease Control and Prevention (CDC) has issued a health advisory, warning doctors across the US to be on the lookout for signs of a strange illness that is attacking children and is associated with Covid-19. 

The condition called the multisystem inflammatory syndrome in children (MIS-C) has been seen in children in the US and across Europe. The mysterious illness in children is potentially related to Covid-19, with symptoms similar to Kawasaki disease and toxic shock syndrome.

“Healthcare providers who have cared or are caring for patients younger than 21 years of age meeting MIS-C criteria should report suspected cases to their local, state, or territorial health department,” says the CDC.

The advisory tells doctors how to spot a patient with the illness, which includes an individual less than 21 years of age, presenting with fever (above 38.0°C or 100.4F for 24 hours or more, or report of subjective fever lasting more than 24 hours), laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (more than two) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); and no alternative plausible diagnoses. 

The case definition includes positive for current or recent SARS-CoV-2 (the virus that causes Covid-19) infection by RT-PCR, serology, or antigen test, or Covid-19 exposure within the four weeks before the onset of symptoms. Abnormal blood tests including an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin, are other signs to look out for. 

“It is currently unknown if the multisystem inflammatory syndrome is specific to children or if it also occurs in adults. There is limited information currently available about risk factors, pathogenesis, clinical course, and treatment for MIS-C. CDC is requesting healthcare providers report suspected cases to public health authorities to better characterize this newly recognized condition in the pediatric population,” says the agency. It adds, “Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C. Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection.”

The CDC advisory tells doctors how to spot a patient with the illness, which includes an individual less than 21, presenting with fever, laboratory evidence of inflammation, positive for current or recent SARS-CoV-2 infection, or Covid-19 exposure within the four weeks before the onset of symptoms (Getty Images)

Doctors in the UK first alerted other doctors to the syndrome in April. Since then physicians in other countries such as Italy and France have reported similar cases. In the US, New York has been hit hard by the syndrome. “During March and April, cases of Covid-19 rapidly increased in New York City and New York State. In early May 2020, the New York City Department of Health and Mental Hygiene received reports of children with the multisystem inflammatory syndrome,” says the CDC.

New York State is currently investigating 110 reported cases and three deaths related to coronavirus Illness in children with symptoms similar to an atypical Kawasaki disease and toxic shock-like syndrome. Children -- predominantly school-aged -- are experiencing these symptoms possibly due to Covid-19, says New York Governor Andrew Cuomo. 

On May 14, Cuomo also announced that New York has issued “first-in-the-nation criteria” to healthcare professionals establishing an interim case definition for Covid-19-related inflammatory illness in children. The criteria established a new name for the syndrome -- pediatric multi-system inflammatory syndrome -- and a definition of what symptoms healthcare providers should look for. Case definitions also help standardize tracking and reporting and can help ensure a better health outcome, say experts. “We're still learning a lot about this virus and we must remain vigilant because the situation is changing every day. We now have 110 cases of Covid-related inflammatory illness in children and I expect this is only going to grow,” said Cuomo. 

Accordingly, New Yorkers have been advised to seek immediate care if a child has symptoms such as prolonged fever (more than five days), severe abdominal pain, diarrhea or vomiting, bloodshot eyes, and skin rash. Other symptoms can include a change in skin color (becoming pale, patchy and/or blue), difficulty feeding (infants) or is too sick to drink fluids, trouble breathing or is breathing very quickly, racing heart or chest pain, and lethargy, irritability or confusion, says the document.

The New York State Department of Health is also partnering with the NY Genome Center and Rockefeller University to conduct a genome and RNA sequencing study to better understand this illness and the possible genetic basis of this syndrome.

Proof of link between Covid-19 and inflammatory condition

Even as the CDC issued the health warning, a detailed report from Italy suggests that Covid-19 may be linked to a rare inflammatory disorder in young children. Doctors in the Bergamo province of Italy have described a series of 10 cases of young children with symptoms similar to the rare inflammatory disease called Kawasaki disease appearing since the Covid-19 pandemic arose in the Lombardy region of Northern Italy.

Only 19 children had been diagnosed with the condition in that area in the five years up to the middle of February 2020, but there were 10 cases between February 18, and April 20, 2020. The latest reports represent a 30-fold increase in the number of cases, although researchers caution that it is difficult to draw firm conclusions with such small numbers. 

Researchers found a 30-fold increased incidence of Kawasaki-like disease (Getty Images)

Eight of the 10 children brought to the hospital after February 18 tested positive for the SARS-CoV-2 in an antibody test. All of the children in the study survived, but those who became ill during the coronavirus pandemic displayed more serious symptoms than those diagnosed in the previous five years, says the report published in The Lancet.

Taken together, the team says that their findings represent an association between an outbreak of SARS-CoV-2 virus and an inflammatory condition similar to Kawasaki disease in Bergamo. According to the experts, this study provides the first clear evidence of a link between SARS-CoV-2 infection and the inflammatory condition.

“We noticed an increase in the number of children being referred to our hospital with an inflammatory condition similar to Kawasaki disease around the time the SARS-CoV-2 outbreak was taking hold in our region. Although this complication remains very rare, our study provides further evidence on how the virus may be affecting children. Parents should follow local medical advice and seek medical attention immediately if their child is unwell. Most children will make a complete recovery if they receive appropriate hospital care,” says Dr Lucio Verdoni, study author from the Hospital Papa Giovanni XXIII in Bergamo, Italy, in the analysis. 

The research team conducted a retrospective review of patient notes from all 29 children admitted to their pediatric unit with symptoms of Kawasaki disease from January 1, 2015, to April 20, 2020. Before the Covid-19 outbreak, the hospital treated around one case of Kawasaki Disease every three months. “Between February 18 and April 20, 2020, 10 children were treated for symptoms of the disease. The increase could not be explained by an increase in hospital admissions, as the number of patients admitted during that time-period was six-fold lower than before the virus was first reported in the area,” says the study.

Dr Annalisa Gervasoni, another author of the study and a pediatric specialist at the Hospital Papa Giovanni XXIII in Bergamo, Italy, said, that while only a small proportion of children infected with SARS-CoV-2 develop symptoms of Kawasaki disease in their experience, it is important to understand the consequences of the virus in children, “particularly as countries around the world grapple with plans to start relaxing social distancing policies.”

“Outbreaks of Kawasaki-like disease might occur in countries affected by the SARS-CoV-2 pandemic, and might present outside the classic Kawasaki disease phenotype. This condition might be serious and requires prompt and more aggressive management,” the team recommends. 

Writing in a linked comment, professor Russell Viner, president of the Royal College of Paediatrics and Child Health and professor of adolescent health, UCL Great Ormond Street Institute of Child Health, UK, says that understanding this inflammatory phenomenon in children might provide vital information about immune responses to SARS-CoV-2 and possible correlates of immune protection that might have relevance both for adults and children. “In particular, if this is an antibody-mediated phenomenon, there might be implications for vaccine studies, and might also explain why some children become very ill with COVID-19, while the majority are unaffected or asymptomatic,” says Viner, who was not involved in the study.

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