Multisystem Inflammatory Syndrome in Children due to COVID-19, Causing Giant Coronary Artery Aneurysms

INTRODUCTION

Children’s multisystem inflammatory syndrome (MIS-C) is a dangerous illness linked to COVID-19. Eighty-two percent of the children with COVID-19 had mild symptoms According to the may 2020 CDC health advisory states that MIS-C is defined as a person under 21 who has a fever, laboratory evidence of inflammation, and signs of a clinically severe illness that requires hospitalization and involves multiple systems (≥ 2) organs “(cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological)” and has no other valid diagnosis. They also have a positive result for a current or recent SARS-CoV2 (COVID 19) infection by reverse transcription polymerase chain reaction (RT-PCR), serology, antigen test, or COVID 19 exposure in the four weeks before symptoms appear.

CASE REPORT

A girl whose 2-year-old came in with a background of fever for 5-day duration with loose stools, vomiting, congested eyes, red, cracked lips, and strawberry tongue. The physical examination findings were unremarkable. Investigations revealed hemoglobin of 12 g, total leukocyte count of 5700 with lymphopenia (absolute lymphocyte count, 1254), platelet count (PLT) of 5.3 lac, erythrocyte sedimentation rate (ESR) of 88 at, COVID 19 immunoglobulin M (IgM), and immunoglobulin G antibodies were negative, C-reactive protein (CRP) of 68 mg/L, D Dimer of 5558 ng/mL, both, IgM Leptospira was negative, and urine routine showing pus cells but urine culture and blood culture showing no growth. The antistreptolysin O titer was negative. This occurred during the second COVID-19 wave in India in September 2021. The child had been exposed to COVID-19, with both the mother and father testing positive. The child’s reverse transcription-polymerase chain reaction was also negative. Echocardiography was performed on day 8 of fever, which showed normal coronaries [Figure 1a-b] with Left Main Coronary Artery (LMCA) - 3.0 mm and Z score - 1.97 mm (1.47–3.0 mm), Left Anterior Descending (LAD) - 2.3 mm and Z score - 1.6 mm (1.02–2.43 mm), left circumflex coronary artery (LCX) - 2.0 mm and Z score - 0.84 mm (0.89–2.45 mm), right coronary artery (RCA) - 2.3 mm and Z score - 0.82 mm (1.19–2.76 mm), and Distal Right Coronary Artery (dRCA) - 1.96 mm and Z score - 0.94 mm (0.87–2.34 mm). Treatment for the patient included methylprednisolone, antibiotics, and aspirin. Fever settled on day 7 of treatment, with a reduction in inflammatory markers. At discharge on oral steroids and aspirin, the child had a CRP of 19.7 mg/L and D-dimer of 1217 ng/mL.

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Figure 1:

Transthoracic echocardiography of parasternal short-axis view-first visit (a) Right coronary artery, (b) Left main coronary artery.

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The child was afebrile for 3 days post-discharge but developed a fever again. On the 19^th day of initial illness, repeat investigations showed features of raised inflammatory markers, with CRP at 36.9 mg/dL, ESR at 77 mm/h, total count at 17800 cells/cm³, and PLT at 10.6 lac. Echocardiography performed at this time revealed a coronary artery aneurysm of all three coronary arteries; both the left main and LAD coronary arteries have a massive coronary artery aneurysm [Table 1 and Figure 2a-d] with trace pericardial effusion.

Table 1: Z-Scores of coronary arteries.

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Figure 2:

Transthoracic echocardiography of parasternal short-axis view-second visit (a) Left main coronary artery, (b) Left circumflex artery, (c) Proximal right coronary artery, (d) Distal right coronary artery.

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She was immediately started on intravenous immunoglobulin (IVIG) infusion of 2 mg/kg for 5 days, methyl prednisolone, aspirin, heparin, and other supportive care. After IVIG infusion, repeat laboratory investigation showed improvements in parameters with hemoglobin (Hb):9.2 g%, CRP:2.9 mg/dL, ESR: 15 mm/h. Compared with pre-IVIG treatment, post-IVIG treatment has shown gross improvement in the laboratory investigations. The percentage of lymphocytes, eosinophils, and PLT significantly increased after IVIG treatment, while the percentage of neutrophils, red blood cell count, Hb, platelet distribution width, CRP, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume-to-lymphocyte ratio significantly decreased.^[1] Echocardiography performed after 1 week revealed a reduction in the z-scores, and she was discharged [Figure 3a-b].

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Figure 3:

Transthoracic echocardiography of parasternal short-axis view– after intravenous immunoglobulin infusion (a) Left main coronary artery, (b) Right coronary artery.

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Repeat echocardiography showed a reduction in the Z-scores, with normal values at 1 year [Figure 4a-b]. Although the sizes were normal, there were irregularities in the LAD; hence, aspirin was continued. At 2 years follow-up, the LAD showed an area of discrete dilatation in the proximal segment of 4 mm (z score −6.15) which was new compared to the previous study. At the 30-month follow-up, echocardiography was performed to reveal z-scores. The patient was asymptomatic. Aspirin was continued, and the child was advised to undergo computed tomography (CT) coronary angiography.

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Figure 4:

Transthoracic echocardiography of parasternal short-axis view-1-year follow-up (a) Left main coronary artery, (b) Right coronary artery.

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DISCUSSION

Children’s multisystem inflammatory syndrome (MIS-C) is a dangerous illness linked to COVID-19. Eighty-two percent of the children with COVID-19 had mild symptoms, while the remaining children showed no symptoms at all. In children who are genetically vulnerable, the pathophysiology of MIS-C is believed to be caused by a hyperimmune reaction to the virus. MIS-C occurred in 4.9% of children, with a low death rate of 2.7%. Up to 67–80% of individuals with MIS-C experience cardiac involvement, which is more prevalent in MIS-C than in Kawasaki disease (KD).^[2] Cardiac manifestations may be in the form of myocarditis (disproportionate tachycardia, left ventricular dysfunction), conduction system abnormalities, and coronary artery aneurysms.^[3] The coronary artery involvement varies from 6 to 24% of cases.^[4] Giant coronary artery aneurysms (Z score >10 or diameter >8 mm) are rare.^[4]

The patient, a 2-year-old girl, had multisystem inflammatory symptoms. While KD is associated with age, the following characteristics set KD apart: Gastrointestinal symptoms, initial lymphopenia, elevated D-dimer levels, exposure to COVID-19 infection, and lack of hand or foot swelling. The MIS-C/KD discrimination score was 73 points (CRP>11 mg/dL (18points) + D Dimer >607 ng/mL (27points) + gastrointestinal involvement (28 units), favoring MIS-C.^[5] MIS-C was the child’s diagnosis and was started on treatment with high-dose corticosteroids with antibiotics and aspirin.^[6,7] Despite initial improvement, the child had a recurrence of fever, and a repeat echocardiography revealed a giant coronary artery aneurysm involving the LMCA and the LAD artery with z-scores of 12.25 and 11.87, respectively.^[8] With z-scores of 5.88 and 6.81, respectively, both the RCA and the LCX were aneurysmal. Giant coronary artery aneurysms in MIS-C with involvement of all three coronary arteries are rare.^[9] The child was started on IVIG and high-dose corticosteroids with dual antiplatelets and unfractionated heparin according to weight (activated partial thromboplastin time being monitored). The child responded to this treatment, and the coronary artery sizes reduced at 1-week post-treatment and normalized by 1 year. The aspirin was continued^[2,8,9,10] because of slight abnormalities in the proximal segment of the LAD artery. At 2-year follow-up, although the sizes of the LAD artery and left circumflex artery remained stable, there was a region of discrete dilatation in the proximal LAD (4 mm, Z score 6.15). Despite the suggestion of a CT coronary angiogram from the beginning, there was no consent from the parents. Hence, the child was continued on low-dose aspirin. The occurrence of new coronary artery aneurysms during convalescence has been reported in MIS-C.^[11] In this instance, the development of new aneurysms after 2 years calls for additional research and long-term monitoring, similar to that of Kawasaki illness.

CONCLUSION

MIS-C is a severe side effect of COVID-19. In this instance, aneurysms of the left circumflex and right coronary arteries, as well as massive coronary artery aneurysms of the LMCA and LAD artery, were found in a child’s case. Despite a good response to treatment initially, with normal sizes at 1 year of age. New aneurysms appeared at the 2-year follow-up in an asymptomatic child. This suggests that long-term follow-up of patients with MIS–C and coronary involvement is necessary. Long-term aspirin therapy is required for these patients. Since this is a new disease starting in mid-2020, only long-term studies will shed more light on the factors leading to progressive disease.