Dubai: Much is already known about COVID-19. But the medical community is yet to fully understand the full extent of the SARS-CoV-2 pandemic.
Paediatricians, for their part, are stumped by an illness in children with possible links to the coronavirus. It shares symptoms with Kawasaki disease, a rare and potentially life-threatening blood condition, which can cause toxic shock.
As of June 21, 2020, more than 8.72 million confirmed cases of COVID-19, including more than 461,000 deaths, based on cases reported to the WHO.
Death risk has been highest in older people and in persons, in particular those with underlying non-communicable diseases — hypertension, cardiac disease, chronic lung disease and cancer.
One of the comforting things about this pandemic is that kids have mostly been spared. However, studies show that children are not immune to the virus SARS CoV-2, though evidence suggests they seem to be only a small minority of those who test positive.
It’s not that simple
Unfortunately, nothing in epidemiology is ever that simple. Clinicians are starting to see a rare but serious complication in children resembling "Kawasaki Disease".
In general, it describes a multi-system inflammatory syndrome in children. The condition is presenting in children who have recovered from COVID-19, or been exposed to people suffering from COVID-19.
It’s not clear if this new cases are actually Kawasaki disease, or just something like it. But the symptoms seem close enough to the doctors, who first began calling it “Kawasaki-like”.
The WHO send out an alert cautioning about an unexplained “Kawasaki-disease-like” hyperinflammatory syndrome in children.
Q: MISC vs PMIS vs PIMS-TS: What’s the difference?
The syndrome has been called different names: Multisystem informatory syndrome in children (MISC) and Paediatric multisystem inflammatory syndrome (PMIS) had been proposed in the US. European doctors proposed the name PIMS-TS (paediatric inflammatorily multisystem syndrome temporally associated with SARS-CoV-2).
Q: What is MISC?
Multisystem inflammatory syndrome in children (MISC) is a condition where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs.
The US CDC warns: "We do not yet know what causes MISC. However, we know that many children with MISC had the virus that causes COVID-19, or had been around someone with COVID-19. MISC can be serious, even deadly, but most children who were diagnosed with this condition have gotten better with medical care".
Q: What's the link between MISC and COVID-19?
On May 13, The Lancet published data about the link between COVID-19 and these symptoms in children in Italy, prompting doctors and experts to research the condition further.
As of May 21, hundreds of cases of MISC cases have been reported in the United States, with dozens more suspected cases checked.
On June 1, 2020, The Lancet published a study conducted by an Italian team which reported "acute myocardial injury", being a novel clinical pattern in children with COVID-19.
Chinese clinicians have reported hundreds of cases, too.
Q: How many children had been reported with MISC?
It is believed to have impacted approximately 300 children in the US alone. The number of could be higher, if cases in Europe and elsewhere were to be accounted for.
In China, of the of 2,135 suspected cases reported to the Chinese CDC (of which 728 were laboratory-confirmed) of COVID-19 among children (median age of all patients was 7 years), 13 were critical, according to a clinical study published in Pediatrics. Regarding the severity (including both confirmed and suspected cases), the Chinese researchers found the following:
- 94 (4.4%) - asymptomatic
- 1,088 (51.0%) - mild
- 26 (38.7%) - moderate
- 13 (0.61%) - critical
Q: When did it emerge?
A June 5, 2020 case report published in the American Journal of Emergency Medicine states that the mysterious syndrome has been linked to COVID-19 and have developed almost about one month after the peak of coronavirus surge across the US.
The case report described features more consistent with a "toxic shock syndrome, but incomplete Kawasaki disease could not be excluded by the patient's overall clinical picture". Researchers added: "It is important to keep Kawasaki disease in mind for potential MISC patients because prompt treatment is low risk and may be beneficial."
Researchers added: "It is important to keep Kawasaki disease in mind for potential MISC patients because prompt treatment is low risk and may be beneficial."
There have been at least five children in the US who have died from the coronavirus-related condition: three in New York State, a 15-year-old girl in Maryland, and a child in Louisiana.
In Italy, children younger than 18 years of age who had COVID-19 composed only 1% of the total number of patients; 11% of these children were hospitalized, and none died, according to an Italian study published on March 26, 2020.
Q: What are the symptoms of MISC?
The most common signs of MISC include fever, respiratory problems requiring oxygen and low blood pressure (hypotension).
Other symptoms in children may include:
- Abdominal pain
- Neck pain
- Bloodshot eyes
- Feeling extra tired
Q: What accounts for the heart dysfunction in children with MISC?
One effect on children who had severe cases of MISC: heart dysfunction. It's still not clear what's the trigger for this.
Dr. James Schneider, head of pediatric critical care at Northwell Health in New York, told a briefing on May 20, 2020. "A striking finding here — alarming — is that in this group, about half the children already had coronary artery abnormalities."
The children were previously healthy, so he thinks the abnormalities were caused by MISC, possibly as a result of a delayed immune response to the coronavirus.
"Any child at home who has fever, abdominal pain or symptoms such as rash and conjunctivitis should be seen by a pediatrician right away," he advised. "I think we need to have a low threshold for evaluation."
More than half of the 33 children treated for MISC at Northwell in April and May had developed some sort of heart dysfunction, Schneider told CNN.
Infectious disease specialist Dr. Nicholas Rister at Cook Children's Medical Center in Fort Worth, Texas, said he has checked several children with a range of symptoms.
"The biggest concern we have right now, especially in kids, is largely stemming from inflammation around the heart," he said. It's one reason doctors at first thought the syndrome was a rare condition known as Kawasaki disease. "And not just the heart but the major vessels around the heart," he added.
Q: What is the WHO case definition of MISC?
The WHO’s preliminary case definition of MISC includes the following:
• Children and adolescents 0–19 years of age with fever >3 days.
Plus two of the following:
1. Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet).
2. Hypotension (abnormally low blood pressure) or shock.
3. Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP),
4. Evidence of coagulopathy (by PT, PTT, elevated d-Dimers).
5. Acute gastrointestinal problems (diarrhoea, vomiting, or abdominal pain).
• Elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin.
• No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes.
• Evidence of COVID-19 (RT-PCR, antigen test or serology positive), or likely contact with patients with COVID-19.
Q: What is Kawasaki disease?
Kawasaki diseases is a rare condition that mostly affects very young children. It shows up in about 10 to 20 out of every 100,000 children under the age of five.
Typical the symptoms of Kawasaki include:
- High, persistent fever
- Widespread inflammation across the body (this can cause swelling of the walls in certain arteries)
- Swollen lymph nodes, particularly near the neck
- Joint pain
- Peeling skin on their hands and feet, around the finger and toe tips
Q: What are the risks if the MISC symptoms are left treated?
Medication usually takes care of fever and inflammation. But doctors warn there can be permanent damage — if the disease is not treated. One report states up to a quarter of untreated children end up with damage to their coronary arteries, the vessels that supply blood to the heart. Kawasaki disease is usually very rare.
Doctors find it a bit strange when they see a bunch of cases that looks a lot like it and pop at the same time, with the emergence of COVID-19.
Q: What’s the most common route of SARS infection in children?
In the previous SARS pandemic, the most common route of infection among children is exposure to infected adults within the same family. A 2003 study of SARS-infected children in Toronto (updated in 2009), showed that clinical disease was mild, nonspecific, and self-limited and was indistinguishable from that reported with other common respiratory viruses.
The factor most strongly associated with SARS-associated coronavirus infection in the children was a history of close contact with an adult SARS coronavirus case, especially in the same household.
Q: What does the WHO say about MISC?
On May 15, 2020, the WHO has published an alert about MISC. Key points of the WHO scientific brief:
- There’s limited data that describe clinical manifestations of COVID-19; evidence associating underlying conditions with severe illness in children is still lacking;
- Manifestation in children are generally milder in children compared with adults;
- Data also show that some children do require hospitalization and intensive care.
- There are relatively few cases of infants confirmed to have COVID-19 have been reported; those who are infected have experienced mild illness.
- Among 345 children with laboratory-confirmed COVID-19 and complete information about underlying conditions, 23% had an underlying condition, with chronic lung disease (including asthma), cardiovascular disease, and immunosuppression most commonly reported.
• Among 345 children with laboratory-confirmed COVID-19 and complete information about underlying conditions, 23% had an underlying condition, with chronic lung disease (including asthma), cardiovascular disease, and immunosuppression most commonly reported.
Q: What treatments were administered on the MISC patients?
The standard first-line treatment for Kawasaki disease — intravenous immunoglobulin (IVIG) — and other immunomodulating therapies used in rheumatoid arthritis (RA) that suppress inflammation have also been used anywhere from 100 per cent to a minority of cases.
Children with MISC have been treated with anti-inflammatory treatment, including:
- Parenteral immunoglobulin
The US National Institutes of Health (NIH) has recommended (data updated June 11, 2020) against routine use of systemic corticosteroids for mechanically-ventilated COVID-19 patients without acute respiratory distress syndrome and only low-dose use for those with refractory shock.
Q: What does the scientific community understand about MISC?
The full spectrum of disease remains unclear, the WHO alert stated. It's also uncertain whether “geographical distribution in Europe and North America reflects a true pattern, or if the condition has simply not been recognized elsewhere.”
The agency urged the world’s medical fraternity, especially paediatricians, to characterise this syndrome and its risk factors, causality, and treatment interventions. “There is, therefore, an urgent need for collection of standardized data describing clinical presentations, severity, outcomes, and epidemiology.”
Q: What should parents do if a child shows concerning signs?
CDC urges parents to seek emergency care right away if your child is showing any of these emergency warning signs of MISC or other concerning signs:
- Trouble breathing
- Pain or pressure in the chest that does not go away
- Inability to wake or stay awake
- Bluish lips or face
- Severe abdominal pain
Q: How will doctors care for your child?
Doctors may provide supportive care for MISC symptoms (medicine and/or fluids to make your child feel better) and may use various medicines to treat inflammation.
Most children who become ill with MISC will need to be treated in the hospital. Some will need to be treated in the pediatric intensive care unit (ICU).
Doctors may do certain tests to look for inflammation or other signs of disease. These tests might include:
- Blood tests
- Chest x-ray
- Heart ultrasound (echocardiogram)
- Abdominal ultrasound
Parents or caregivers who have concerns about their child’s health, including concerns about COVID-19 or MISC, should call a pediatrician or other healthcare provider immediately. The CDC also has a set of recommendations for healthcare providers to keep children and their parents or caregivers safe if an in-person visit is needed.