An otherwise healthy 12-year-old boy was admitted to a peripheral hospital (Lombardy – northern Italy), with complaints of fever, vomiting, diarrhoea and drowsiness for the previous three days. Though no respiratory symptoms were reported, both his parents have been presenting with cough and low-grade fever for several weeks. Patient’s past medical history was unremarkable.
On admission, blood tests showed normal full blood count but raised CRP (23.4 mg/dL, reference range < 0.5) and procalcitonin (PCT – 3.3 ng/ml, reference range < 0.5). Despite negative findings at chest x-ray, based on the clinical and family history, COVID-19 was suspected and a nasopharyngeal swab was performed, showing positive result for SARS-CoV-2 infection by real-time reverse transcriptase–polymerase chain reaction (RT-PCR). Later, also nasopharyngeal swab of patient’s father revealed to be positive.
Twenty-four hours later, a remarkable increase of both CRP (33.1 mg/dL) and PCT (44.22 ng/ml) prompted the collection of peripheral blood culture, the start of systemic antibiotic treatment with intravenous Ceftriaxone and patient’s transferral to the Pediatric Department of our tertiary care Centre.
Upon arrival, the patient was ill-appearing, highly febrile (body temperature: 39.0°C) and tachycardic (140 beats per minute), though he presented with normal blood pressure (110/70 mmHg) and room-air pulse-oximetry (98%).
Repeated laboratory investigations showed a further worsening of inflammation markers (CRP 43.11 mg/dL, PCT 58.84 ng/mL), neutrophilia (neutrophils 12.18 x103/µL) and raised D-Dimer (2396 ng/mL, reference range <250), with an International Normalized Ratio (INR) of 1.4 and increased lactate (4 mmol/L). Venous gas analysis and baseline electrocardiogram provided normal results.
Given the overall worsening of both clinical and biochemical picture despite ongoing antibiotic treatment, Ceftriaxone was empirically switched to a combination of intravenous meropenem and vancomycin. In addition, antithrombotic therapy with intravenous unfractioned heparin was introduced.
In a few hours the child developed severe hypotension (blood pressure: 70/40 mmHg) and clinical signs consistent with progressive peripheral hypoperfusion, refractory to intravenous fluid resuscitation (saline solution: 20 mL/Kg in 15 minutes) and vasoactive amines infusion (norepinephrine). Urgent bedside echocardiography showed a severe decrease in ventricular systolic function, with a left ventricle ejection fraction (LVEF) of 25%, increased left ventricular dimensions with diffuse hypokinesis but retained right ventricular function. Both troponin T (TnT, 602 ng/L with reference range < 14) and N-terminal brain natriuretic peptide (NT-proBNP, 27075 pg/mL with reference range < 300) were found to be remarkably raised.
Due to a progressive deterioration of the clinical picture and the need for mechanical ventilation, invasive hemodynamic monitoring and combined norepinephrine and dobutamine infusion, the patient was transferred to our Intensive Care Unit (ICU).
As showed in figure 1, after an initial improvement, the patients experienced a steep exacerbation of both clinical and biochemical data within 48 hours. Interleukin-6 was tested at this stage and showed a peak value of 8209 pg/ml (reference range: < 7). A chest and abdomen CT scan showed radiological signs consistent with uncomplicated colitis, while pulmonary findings were unremarkable.
The patient was therefore started on antiviral treatment with remdesivir, an investigational nucleoside analogue prodrug with supposed efficacy on SARS-CoV-2, at the loading dosage of 200 mg, followed by 100 mg every 24 hours. Vancomycin was discontinued and replaced with tigecycline and clindamycin, while treatment with meropenem was continued unchanged. Support therapy including vasoactive and inotropic amines, short course hydrocortisone (due to its mineralocorticoid effect), furosemide and captopril was undertaken. With the exception of SARS-CoV-2, all the remaining microbiological investigations performed yielded negative results, including peripheral blood cultures for fungi and bacteria and serologies for cardiotropic infectious agents (echoviruses, coxsackieviruses, cytomegalovirus, adenovirus and mycoplasma) and PCR essays on blood and stool for enterovirus genus nucleic acids.
During the following days, patient’s clinical condition progressively improved. Figure 1 shows how the gradual drop of inflammation and myocardial damage markers corresponded to a concomitant increase of LVEF, leading to restoration of cardiac function by the fifth day of intensive care. In two additional days’ time, the patient was progressively weaned from vasoactive support and definitely extubated. The SARS-CoV-2-targeted nasopharyngeal swab and bronchoalveolar lavage performed seven days after the start of antiviral treatment showed negative results, and remdesivir was therefore discontinued.
Gadolinium-enhanced cardiac Magnetic Resonance Imaging (MRI), performed on day 13, detected an area of subepicardial delayed enhancement within the left ventricle, consistent with recent myocarditis (See figure 2 for detailed description of radiological findings).
After 21 days of hospitalization, the child was discharged with no sequelae.