A previously healthy 18-year-old African American female presented to the emergency department (ED) with four days of fever, fatigue, headache, sore throat, odynophagia, abdominal pain, vomiting, and diarrhea. Prior to presentation to the ED, she had been tested negative for Group A Streptococcus, influenza, mononucleosis, and SARS-CoV-2. She completed her Pfizer-BioNTech mRNA COVID-19 two-dose vaccine series six months ago, and two months prior to presentation, she had started college and received weekly SARS-CoV-2 testing (rapid antigen) as part of routine screening (all negative). She had no known symptomatic SARS-CoV-2 infection.
In the ED, she was afebrile, tachycardic at 127 beats per minute and hypotensive with a blood pressure of 86/53 mmHg. On exam, she had tender bilateral cervical lymphadenopathy, trismus, fullness on the left side of her neck, and decreased range of neck motion. Her initial workup was significant for leukocytosis, elevated CRP (Table 1), and negative SARS-CoV-2 PCR. Neck commuted tomography (CT) scan demonstrated a retropharyngeal fluid collection (6.1 x 2.7 x 0.5 cm) extending from C1 to C4 vertebral body level (Fig. 1). A diagnosis of retropharyngeal phlegmon was made and IV ampicillin-sulbactam was started in addition to a single dose of dexamethasone for airway edema.
Table 1
Lab Results on Admission, Hospital Day 1 (Transfer to PICU), and Initial Response to IVIG
| Lab (Reference Range) | | Admission | Hospital Day 1 | Post IVIG |
| White Blood Cells (3.9–10.7 × 103/µL) | 13.8 | 19.0 | 29.3 |
| Hemoglobin (11.8–16.0 gm/dL) | 12.0 | 9.4 | 9.0 |
| Platelets (135–371 × 103/µL) | 200 | 224 | 271 |
| Neutrophils (absolute) (1.60–8.10 × 103/µL) | 12.22 | 17.20 | 22.80 |
| Lymphocytes (absolute) (1.10–3.50 × 103/µL) | 0.48 | 1.50 | 1.03 |
| C-Reactive Protein (0.1–1.7 mg/L) | 400.7 | 352.9 | 118.6 |
| Procalcitonin ( < = 0.24 ng/mL) | | > 100.00 | |
| Creatinine (0.60-0-.88 mg/dL) | 1.04 | 0.94 | 0.56 |
| Aspartate Aminotransferase (13–35 unit/L) | 66 | 44 | 57 |
| Alanine Aminotransferase (8–24 unit/L) | 44 | 36 | 24 |
| Bilirubin Total (0.1–0.8 mg/dL) | 1.3 | 0.9 | 0.6 |
| Lactate Whole Blood (0.5–2.2 mmol/L) | | 5.7 | 2.1 |
| Troponin-I ( < = 0.03 ng/mL) | | 0.22 | 0.18 |
Table 1. Laboratory findings relative to MIS-C targeted interventions.
Figure 1. CT of the Neck
CT of the neck demonstrating a retropharyngeal fluid collection presumed to be the source for the patient’s original presentation. Arrows indicate sagittal view of retropharyngeal fluid collection measuring 6.1 cm, from C1 to C4 (left) and a coronal view of retropharyngeal fluid collection measuring 2.7 x 0.5 cm (right).
On the day after admission [Hospital Day (HD) 1], she was tachycardic to the 150s, hypoxemic requiring supplemental oxygen by nasal cannula, and developed fluid refractory hypotension with blood pressures of 70s/50s mmHg. She was transferred to the pediatric intensive care unit and started on norepinephrine for presumed septic shock. Labs were notable for elevated procalcitonin, lactate and troponin, in addition to persistent leukocytosis (Table 1). Antibiotics were broadened from ampicillin-sulbactam to vancomycin, clindamycin, and levofloxacin. Echocardiogram (ECHO) showed markedly depressed biventricular function with a left ventricular ejection fraction (LVEF) of 22%. Norepinephrine was transitioned to epinephrine for inotropic support and dobutamine was added. Respiratory support was escalated to high flow nasal cannula and briefly to bilevel positive airway pressure due to hypoxemia and increased work of breathing.
On HD 2, she remained febrile, tachycardic, and tachypneic despite a repeat neck CT that demonstrated moderate decrease in the retropharyngeal fluid collection. Repeat ECHO demonstrated improvement in cardiac function with LVEF of 42% while on vasopressors. On HD 3, her antibiotics were broadened to vancomycin, cefepime and metronidazole to cover for indolent infection given her lack of clinical improvement and persistently elevated CRP to 415mg/L.
Given her continued critical illness on multiple vasopressors and broad-spectrum antibiotics, MIS-C was considered in the differential diagnosis, and the decision was made to administer intravenous immune globulin (IVIG). She received IVIG on HD 3 and received a total of 2g/kg of IVIG over the course of four days (HD 3 - HD 6). After initiation of IVIG, she began to defervesce (afebrile for 24 hours by HD 5), and her CRP and lactate improved (Table 1). Her ventricular function improved on ECHO (LVEF 55% on HD4 with continued vasopressor support). On HD 6, her COVID-19 IgG (drawn prior to IVIG treatment) to nucleocapsid protein returned positive, and the diagnosis of MIS-C was made. Anti-inflammatory treatment for MIS-C was initiated with intravenous methylprednisolone and subcutaneous anakinra. On HD 7, she was able to be weaned from all vasopressor support and was transferred back to the to the acute care floor where she continued to recover. ECHO on HD 9 demonstrated normal biventricular function. She was discharged home on HD 10 with subcutaneous anakinra and continued steroids. (Fig. 2).
Figure 2. Key Events Timeline
A timeline demonstrating key events in the chronology of the patient’s presentation and subsequent interventions. PICU - pediatric intensive care unit; IVIG, intravenous immunoglobulin; MIS-C, multisystemic inflammatory syndrome in children.
She had an ECHO at her follow up appointment with Cardiology 12 days after discharge which showed an LVEF of 59% with no valve or coronary abnormalities. She completed anakinra and prednisone tapers per instructions by Pediatric Rheumatology. Cardiac magnetic resonance imaging (MRI) was obtained three weeks after discharge with normal EF without evidence of myocardial inflammation by parametric mapping and there was no late gadolinium enhancement of the myocardium. Per patient report she has made full recovery with no sequelae.