COVID-19 and MIS-C (Multisystem Inflammatory Syndrome in Children)

Introduction:

MIS-C, otherwise called multisystem inflammatory syndrome in children, is a potentially fatal and rare condition that affects children. It is being linked to the infection caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus, which is COVID-19. Even though most children infected with this new virus show relatively mild symptoms or are asymptomatic, some develop MIS-C. This condition can affect some or all organs and tissues in the body, such as the lungs, heart, kidneys, blood vessels, digestive tract, brain, eyes, and skin. The affected organs become severely inflamed. Most children recover from this syndrome with proper medical care. But in some children, the condition can result in fatal complications.

In children, symptoms similar to Kawasaki disease (KD) or toxic shock syndrome (TSS) was first reported in the United Kingdom. As similar symptoms were also reported in other parts of the world, the condition was named multisystem inflammatory syndrome in children (MIS-C). The other names include pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), pediatric multisystem inflammatory syndrome (PMIS), pediatric hyperinflammatory shock, and pediatric hyperinflammatory syndrome.

MIS-C is not a disease, but a collection of signs and symptoms, or in other terms, a syndrome, and a lot is unknown about it, such as the risk factors and cause. Depending on the organ or organs affected, the signs and symptoms of MIS-C vary. Only by evaluating more children with COVID-19 and MIS-C will we be able to identify the cause. The CDC (Centers for Disease Control and Prevention) and the NIH (National Institutes of Health) are working around the clock to find the risk factors and cause of MIS-C to diagnose and treat this syndrome effectively. Let us see what we know so far about this syndrome.

What Are Kawasaki Disease and Toxic Shock Syndrome?

Kawasaki Disease (KD) - Kawasaki disease is also a syndrome of unknown etiology that commonly affects children younger than 5 years. This condition results in inflammation of the blood vessels' walls throughout the body and can also affect the coronary arteries and heart.

MIS-C with Kawasaki disease is characterized by fever, conjunctival redness, cracked lips, strawberry tongue, rash, swollen and erythematous hands and feet and cervical lymphadenopathy.

Toxic Shock Syndrome(TSS) - TSS is a rare and potentially fatal complication of infection caused by the bacteria Staphylococcus aureus. This condition is caused when this bacteria enters the blood and produces toxins.

How Does SARS-CoV-2 Cause MIS-C?

It is not well understood how SARS-CoV-2 causes MIS-C. Scientists believe that this syndrome is caused by an abnormal response of the immune system to the Coronavirus. How this virus triggers the abnormal immune response is still not known. Most children exhibit symptoms of MIS-C test negative for SARS-CoV-2 through polymerase chain reaction (PCR) but have positive serology. This confirms that MIS-C results from an altered immune response after the infection's acute phase is over. It is still not clear why some children develop MIS-C following COVID-19, but others do not. However, it can also occur rarely in adults who were previously diagnosed with the Covid-19 virus and may not even know about it. It can occur weeks after the Covid-19 infection.

Risk Factors:

More Hispanic and African-American children have been affected by MIS-C in the US. However, it is still unknown why children of these ethnic groups get infected with MIS-C. Children of all ages can get affected, but MIS-C is commonly seen between 3 and 12 years old, with an average of eight years.

What Are the Reported Signs and Symptoms of MIS-C?

Based on the documented cases so far, children that present with MIS-C exhibit the following symptoms.

• Fever that lasts for four to six days.

• Stomach pain.

• Fatigue.

• Rashes

• Cough.

• Inability to wake up or stay awake.

• Neck pain.

• Sore throat.

• Body pain.

• Increased heart rate.

• Shortness of breath.

• Diarrhea and vomiting.

• Skin rashes.

• Pink eyes (conjunctivitis).

• Headaches.

• Confusion.

• Bluish lips.

• Swollen hands or feet.

• Swollen tongue and lips.

• Dizziness.

• Swollen lymph nodes.

Fever is the most common symptom, and gastrointestinal symptoms can mimic appendicitis pain. Some children also exhibit neurologic symptoms, such as seizures, coma, and muscle weakness.

If your child has a severe stomach ache, breathing problems, confusion, bluish face or lips, and is unable to stay awake, seek immediate medical help.

What Are the Clinical and Laboratory Findings in Children With MIS-C?

On clinical examination, such children showed:

1. Fissured lips.

2. Strawberry tongue.

3. Red and swollen extremities.

4. Swollen cervical lymph nodes.

5. Arrhythmia (irregular or fast heartbeat).

6. Acute respiratory failure.

7. Swollen liver.

8. Swelling of the brain and surrounding membranes.

And laboratory findings include:

1. Mild anemia.

2. Lymphocytopenia (low lymphocytes).

3. Neutrophilia (high neutrophils).

4. Thrombocytopenia (low platelets).

5. Raised cardiac markers, such as troponin.

6. Elevated inflammatory markers, such as CRP (C-reactive protein), erythrocyte sedimentation rate (ESR), Ferritin, Interleukin-6 (IL-6), D-dimer.

7. Hypoalbuminemia (low albumin in the blood).

8. Raised lactate dehydrogenase.

9. Hypertriglyceridemia (elevated blood triglycerides).

10. Slightly elevated liver enzymes.

11. There will be evidence of recent COVID-19 infection or likely contact with COVID-19 patients. So the RT-PCR antigen test or serology will be positive.

What Are the Possible Complications of MIS-C?

If the doctor suspects MIS-C, he or she will run various tests to see how well the heart, kidneys, and liver are functioning and if there is any inflammation. Polymerase chain reaction (PCR) and serology for SARS-CoV-2 are essential to detect an acute COVID-19 infection or detect antibodies that suggest past infection. A positive serology result indicates the child's immune system produced antibodies to fight the SARS-CoV-2 virus. Apart from this, the following tests might be needed:

1. Complete blood count (CBC) with differential

2. C-reactive protein (CRP) and erythrocyte sedimentation rate for inflammation.

3. Liver function tests.

4. Chest X-ray.

5. Abdominal ultrasound.

6. Heart ultrasound (echocardiogram).

7. Serum electrolytes and kidney function tests.

8. Urinalysis.

9. Prothrombin time.

10. Cardiac markers such as Troponin and Brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-pro-BNP).

Following tests might be needed to rule out other conditions that result in similar symptoms:

1. Blood culture.

2. Urine culture.

3. Throat culture.

4. Stool culture.

5. Serology or PCR for Epstein-Barr virus, Cytomegalovirus, Enterovirus, and Adenovirus.

6. Tests for typhoid and leptospirosis.

How Is MIS-C Treated?

Hospitalization, and sometimes treatment in the pediatric intensive unit, is needed for most children. As there is no cure, treatment is focused on reducing inflammation and symptoms. It is important to protect vital organs and prevent permanent damage. Depending on the affected organ and the severity of symptoms, the treatment options include:

1. Intravenous fluids to prevent dehydration.

2. Oxygen therapy to assist with breathing.

3. If the blood pressure is too low, blood pressure stabilizing medications are administered. This helps the heart function properly and pump blood throughout the body.

4. Ventilator support if the lungs are not functioning properly.

5. Antibiotics to treat any secondary bacterial infection.

6. Steroids to reduce inflammation. Taper steroids for two to three weeks with clinical and CRP monitoring.

7. Immunoglobulin intravenously. These are antibodies that help the patient recover.

8. Aspirin, Heparin, or other blood thinners to reduce the risk of blood clots.

9. For children with cardiac involvement ECG has to be repeated 48 hourly and ECHO at 7 to 14 days and between 4 to 6 weeks, and after one year if initial ECHO was not normal. If the heart and lungs are severely affected, extracorporeal membrane oxygenation (ECMO) might be needed.

Even though MIS-C is not contagious, the child could still have an active COVID-19 infection or some secondary contagious infection. So, infection control measures should be employed at all times.

Prevention:

As MIS-C is linked to COVID-19, the best way to prevent this syndrome is by avoiding exposure to the SARS-CoV-2 virus. Teach your child how this virus spreads and what they can do to keep themselves safe. Make sure:

1. Your child keeps his hands clean and washes them frequently with soap and water for at least 20 seconds. You can also teach them how to use alcohol-based hand sanitizers.

2. You do not let people who are visibly sick come close to your child.

3. Your child knows the importance of social distancing. Ask them to stay six feet or more away from other people when they go out.

4. Your child wears a face mask in public (only if the child is older than two years, and he or she can take the mask off themselves).

5. Your child does not touch his or her face without washing their hands first.

6. Your child covers the mouth while sneezing to avoid spreading germs.

7. Make your child get COVID vaccination. Pfizer-BioNTech and Moderna vaccines are used in the clinical trials of children aged six months, children above six months, and teenage people. These trials are made to come to a conclusion about COVID-19 vaccines for children. The Pfizer vaccine has been given permission for use in people 16 years of age and older and subsequently in children of 12 to 16 years of age and in the pediatric population of ages 5 through 11 years, with a change in the recommended dosage. Now the company is testing the vaccine’s efficacy in infants and children up to the age of five. Moderna vaccine has been approved as a COVID-19 vaccine for children above 18 years of age or older by the Centers for Disease Control and Prevention, United States (CDC), and six years or older by the European Medicines Agency. Covaxin was given approval for emergency use in children aged two years to 18 years years. The clinical trials in children are ongoing, and the vaccine’s efficacy and immune response generated were found to be similar to that of adults in the trials.

As a parent, you should clean and disinfect all the frequently touched surfaces, such as switches, remotes, chairs, tables, etc., at home every day with a good disinfectant. Wash your child's clothes using the warmest setting in the washing machine. Also, wash or wipe their toys regularly. In addition, it is essential to get vaccinated on your turn for further protection and to prevent the spread of COVID-19.