PMC7350897_01
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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F1
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).
Timeline of main pharmacologic interventions.
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F2
Her condition deteriorated quickly despite antibiotic therapy (Figure 2), necessitating hospital admission 5 days after onset of the disease.
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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F3
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.