case_images: PMC7350897_01
case_images: Exanthema on day 12 (A). Blood biochemistry and markers of inflammation over the course of the disease (B). Chest X-ray on day 6 showing only mild signs of hypoventilation in the retrocardiac region with no infiltration or consolidation (C). Soluble IL-2 receptor and plasma IL-6 levels (D).
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case_images: F1
case_images: Here we report a case of an 8-year-old girl who manifested with fever (>40 C), headache, abdominal pain, vomiting, diarrhea, and diffuse itchy maculo-papular rash (Figure 1A), but no signs of respiratory involvement. At admission she had high inflammatory markers (Figure 1B), elevated D-dimers, urea, creatinine, liver enzymes, troponin, and proNT-BNP. No microbiological (blood culture, panbacterial 16S PCR, herpes family PCR, endotracheal aspirate culture, viral and atypical pneumonia PCR, urine culture) or imaging tests (for chest X-ray, see Figure 1C) could explain all her symptoms. The persistent elevation of CRP (199 mg/l), procalcitonin (28.4 mug/l), soluble IL-2 receptor (6,326 IU/ml, Figure 1D), ferritin (577 mug/l), and history of juvenile idiopathic arthritis (oligoarticular subtype, currently inactive without therapy) lead to suspicion of viral-induced macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis (HLH), which however was not abundantly present in bone marrow aspirate and the patient did not fulfill the classification criteria for MAS/HLH (triglycerides 0.72 mmol/l, fibrinogen 3.8 g/l, platelets 200 x 109/l).
case_images: Timeline of main pharmacologic interventions.
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case_images: F2
case_images: Her condition deteriorated quickly despite antibiotic therapy (Figure 2), necessitating hospital admission 5 days after onset of the disease.
case_images: Leukocyte subpopulations over the course of the disease (A). Complement protein C3 and C4 levels over the course of the disease (B). Neutrophil phenotype on day 8 (fulminant disease), 12 and 19 (recovery) in comparison to a healthy control (C).
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case_images: F3
case_images: Soluble IL-2 receptor, produced primarily by activated mononuclear cells, was remarkably high, although both monocytes and lymphocytes were normal on day 8 and increased only slightly between days 10 and 15 (Figure 3A). In addition to the elevation of granulocytes and low CD8 T cell and NK cell counts, we also illustrate the pivotal role of innate immunity in defense against SARS-CoV-2 by the depletion and gradual recovery of complement (C3, C4 proteins, Figure 3B). We additionally show significant changes in neutrophil phenotype (Figure 3C) during the course of the disease, such as a decrease in neutrophil HLA-DR expression, as previously described in COVID-19.