Multisystem Inflammatory Syndrome in Children After Breakthrough Infection in a COVID-19-vaccinated Child.

To the Editors:

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare hyperinflammatory condition requiring a high index of suspicion, as the differential diagnosis is broad, and patients often present critically ill.[1] MIS-C has not been reported after breakthrough infection in children who have completed mRNA coronavirus disease 2019 (COVID-19) vaccination.

A 13-year-old male who received 2 doses of the Pfizer/BioNTech vaccine (BNT162b2) 13 weeks before admission presented with 3 days of fever, abdominal pain, nausea, and vomiting. Six weeks earlier, following a family exposure, he had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by nasopharyngeal nucleic acid amplification test while asymptomatic. On arrival, he was febrile to 100.8°F, hypotensive, and ill appearing with diminished capillary refill time. Despite 2 normal saline boluses, his blood pressure remained, and he was started on epinephrine before being admitted to pediatric intensive care unit. An abdominal ultrasound to evaluate the appendix was ordered, and further workup for possible MIS-C diagnosis was performed (Table 1). His abdominal ultrasound showed a normal appendix. His EKG and echocardiogram were normal. Despite the improvement in his blood pressure after 24 hours, he remained tachycardic with elevated D-dimer levels. His chest computed tomography was negative for a pulmonary embolus. He remained febrile with abdominal pain and subsequently developed an erythematous macular rash on his chest and palms, nonexudative conjunctivitis, and periorbital edema and erythema. Given his negative cultures and development of mucocutaneous signs, he was given the diagnosis of MIS-C and treated with intravenous immune globulin and methylprednisolone. His fever and mucocutaneous signs resolved, and his C-reactive protein improved. Two weeks after his discharge, he only had mild fatigue. His cardiac magnetic resonance imaging demonstrated mild biventricular dilation with normal function, a trivial pericardial effusion and no myocarditis. His coronary arteries were normal. Written parental consent for this report was obtained.

TABLE 1.

Laboratory Parameters at Outside Hospital, on Admission to Our Center, on the Day of Discharge and at 2 Weeks Follow-up Evaluation

Laboratory Tests*	Outside Hospital	Admission	1 Day Before Discharge	2-Week Follow-up
WBC (4.5–13.5 109/L)	4.93	3.4	8.8	5.7
Hemoglobin (12.5–16.4 g/dL)	13.1	12.5	11.4	12.6
Hematocrit (37.0%–49.0%)	38.1	37.1	33.3	38.2
Platelets (142–508 109/L)	188	162	367	380
Absolute lymphocyte count (109/L)	0.31	0.5	2.8	1.5
CRP	89.4 (0.0–10.0 mg/L)	21.7 (<1.0 mg/dL)	5.8 (<1.0 mg/dL)	<0.5 (<1.0 mg/dL)
Procalcitonin (<0.5 ng/mL)		2.4	<0.5
Sedimentation rate (<13 mm/h)		15	33	35
Interleukin 6 (<10 pg/mL)		211.2
Ferritin (7–142 ng/mL)		218		128
Quantitative D-dimer [<0.50 μg(FEU)/mL]		1.96	3.28	0.44
Fibrinogen (170–410 mg/dL)		429	302
Sodium	130	133	136	137
AST (15–50 U/L)		46	90	40
ALT (<36 U/L)		22	57	40
BNP (<60.0 pg/mL)		160.7	280.9
Troponin (<0.029 ng/mL)		<0.010	<0.010	<0.010
SARS-CoV-2 NC IgG antibody [<1.40 (Index S/C)]		3.12

Normal values are given in parenthesis.

ALT indicates alanine transaminase; AST, aspartate aminotransferase; FEU, fibrinogen equivalent units; NC, nucleocapsid; WBC, white blood cell count.

Vaccination against SARS-CoV-2 infection has been one of the most effective tools to bring the pandemic under control, lowering the risk of infection, hospitalization, and death.[2] The possibility of MIS-C following COVID-19 vaccination in children has been carefully considered and, to our knowledge, has not been reported to this date, whereas multisystem inflammatory syndrome in adults has been reported in 2 patients following vaccination.[3,4] One of these patients received the BBIBP-CorV (Sinopharm) inactivated vaccine shortly after COVID-19 infection and 6 weeks later presented with multisystem inflammatory syndrome in adults symptoms within hours after their second vaccine dose.[3] The second patient developed symptoms 2 days after the first dose of Pfizer/BioNTech mRNA vaccine and was also diagnosed with pulmonary embolism and acute kidney injury.[4] Our patient was diagnosed with MIS-C 6 weeks after an asymptomatic breakthrough SARS-CoV-2 infection and 13 weeks after completing Pfizer/BioNTech vaccination, suggesting that the mild infection, rather than the vaccination, triggered the hyperinflammatory response.

This case highlights the critical need for reporting symptoms associated with breakthrough infections and monitoring for symptoms of MIS-C. Clinicians should continue to be vigilant of signs and symptoms of MIS-C irrespective of vaccination status.