MIS-C: Fight of the COVID-Survivors

What Is MIS-C?

First reported in medical literature in April 2020, MIS-C, which stands for multisystem inflammatory syndrome in children, as the terminology suggests, is a rare inflammatory syndrome affecting multiple organ systems in children, often secondary to COVID-19 infection.

This came into focus when clusters of children got admitted with a range of symptoms with multisystemic inflammation clinically similar to Kawasaki disease. MIS-C can cause inflammation in various internal and external organs, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal tract. This is seen two to six weeks after a primary COVID-19 infection, usually, after the child has recovered, but occasionally may also co-exist with asymptomatic COVID-19.

Who Is Susceptible to MIS-C?

The incidence of MIS-C in the population below the age of 21 was about 316 per one million COVID patients, which is roughly about one in 3000. The median age of patients is about nine years, with less than a quarter of the cases having any prior comorbidities. The incidences were observed to be higher in Black, Hispanic, and Latino children, but COVID-19 rates could not explain the high incidence of MIS-C among blacks.

What Causes MIS-C?

The exact cause of MIS-C has not been identified yet, however studying the hospitalization trend has given rise to a hypothesis. It was observed that children with a recent history of COVID-19 infection, some even presented with an active infection. The hypothesis suggests that a COVID-19 infection preps the immune system to overreact, which is what is seen in MIS-C.

The risk factors of MIS-C include young age (between five and 11 years). However, children with a one-year age and also 15 years of age have been admitted with MIS-C. It is also hypothesized that one particular variant of SARS-CoV-2 is more likely to precipitate MIS-C than others, and only a certain school of children is more susceptible. CDC (Centers for Disease Control and Prevention) is still trying to find the etiology and pathophysiology of MIS-C and its link to COVID-19.

What Are the Clinical Features of MIS-C?

The clinical features of MIS-C are quite severe and may require hospitalization and specialized care. The symptoms also tend to vary among the affected children. Some of the symptoms of MIS-C include the following:

• History of active COVID-19 infection or close contact with a COVID patient.

• Fever.

• Systemic inflammation (evident with a blood report).

• Heart issues.

• Red, bloodshot-like eyes.

• Redness with swelling of the lips and the tongue.

• Redness or swelling of the hands or feet.

• Pain in the stomach with, vomiting, or diarrhea.

• Blood clotting issues.

• Shock.

Not all patients present with all of the above symptoms or even the same ones.

Some of the signs that indicate the need for emergency care are:

• Severe stomachache.

• Pain in the chest or a feeling of pressure.

• Breathing problems.

• Pale gray or blue skin, lips, or nail beds.

• Confusion.

• Inability to wake up or remain awake.

How to Diagnose MIS-C?

The diagnosis is based on the principle of exclusion wherein the doctor may reach an MIS-C diagnosis after eliminating all possible differentials. However, to confirm, multiple tests are ordered to verify the same.

• Laboratory Studies: Acute phase reactants, like CRP (C-reactive proteins), are markedly elevated. RT-PCR (reverse transcriptase polymerase chain reaction) or antigen test confirms the presence of active or history of COVID-19. COVID-vaccinated individuals may report anti-spike IgG antibodies and not anti-nucleocapsid IgG antibodies. Troponin and BNP/NT-Pro BNP levels are also increased. Changes in cardiac markers level are tracked to predict the possibility of cardiac complications, as cardiovascular diseases can further worsen MIS-C progression.

• Echocardiogram: Up to 40 % of the patients might show left ventricular systolic with or without diastolic dysfunction in echo images. Mitral regurgitation is seen in about 30 % of cases, pericardial effusion in 20 %, and a possibility of coronary artery dilation in about 13 % of cases during active pathology or after remission.

• Electrocardiogram (ECG): Abnormal ECG patterns may be noted in approximately 35 percent of cases. The ECG reading may represent ST or T-wave abnormalities and transient QTc prolongation. Transient first and second-degree AV-block (atrioventricular block) have been reported through ECG readings.

• Urine and Imaging Test: Additionally, urine tests to measure the level of inflammatory proteins and imaging tests like X-Rays, abdominal ultrasound, and CT (computed tomography) scans may also be ordered to procure additional diagnostic evidence.

How to Treat MIS-C?

Due to lack of sufficient research and studies, the guidelines are based on clinical consensus rather than absolute scientific evidence.

Supportive therapy is provided which includes:

• Fluid resuscitation.

• Inotropes.

• Mechanical ventilation.

• ECMO (extracorporeal membrane oxygenation).

Owing to its possible association with infection, antibiotics therapy is prescribed. However, with the hypothesized post-infectious origin of MIS-C, immunomodulators (like Anakinra and Tocilizumab) are necessary. Children have been successfully treated with IVIG (intravenous gamma globulins) and corticosteroids. The IVIG-steroid combination has given a more favorable result. Additionally, antiplatelets, interleukin-6 inhibitors, and interleukin-1Ra inhibitors have been successfully used for remission. Prophylactic anticoagulation is also given to hospitalized patients to counteract the risk of thrombosis.

What Is the Prognosis of MIS-C?

In the short term, about 65 % of individuals require intensive care, with half of them requiring inotropic support. The hospital stay might extend up to five days. The mortality rate, as reported by CDC, is about 0.9 percent, which is also on the decline. It is worthwhile to note that:

• Ventricular dysfunction recovers within a few days and the coronary ectasia (dilation of the coronary artery lumen) and small aneurysms regress.

• Some symptoms like neurologic abnormalities, muscle weakness, easy fatigability, anxiety, emotional lability, and postural orthostatic tachycardia syndrome (POTS-tachycardia that occurs when standing up) may persist for longer.

• Long-term prognostic studies are yet to report findings.

What Is the Differential Diagnosis of MIS-C?

• Bacterial sepsis.

• Toxic shock syndrome.

• Kawasaki disease (KD).

• Appendicitis.

• Hemophagocytic lymphohistiocytosis (HLH-histiocytes and lymphocytes attack other blood cells).

• Macrophage activation syndrome (MAS- macrophages attack other blood cells).

• Rickettsia (a vector-borne bacterial disease).

• Viral syndrome (cytomegaly, Epstein-Barr, adenovirus, Coxsackie, varicella, etc.).

• Bacterial enteritis (bacterial gastrointestinal problem).

• Lupus (an autoimmune disorder).

• Vasculitis (blood vessel inflammation).

What Are the Complications of MIS-C?

• Myocarditis.

• Coronary artery aneurysms.

• Multiorgan failure.

• Irreversible organ damage.

• Death.

Conclusion

MIS-C is a novel pediatric syndrome characterized by multisystemic organ manifestations. Even though the guidelines are unclear, the accepted norms have given satisfactory outcomes. It is essential to vaccinate as soon as it is available for the age groups concerned as the benefits outweigh the risks. Since it is likely associated with COVID-19, it is recommended to follow COVID-prevention guidelines which serve better than having to deal with future COVID or MIS-C. It is advisable to wait for 90 days following acute illness to ensure adequate cardiac recovery before opting for COVID vaccinations.