Mycophenolate mofetil/tacrolimus

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 16-year-old boy developed COVID-19 infection during immunosuppressive treatment with mycophenolate mofetil and tacrolimus.

The boy, who underwent cardiac transplantation, had been receiving immunosuppressive treatment with mycophenolate mofetil 360mg (two tablets) twice a day and tacrolimus 2.5mg twice daily [routes not stated]. Three months post-transplant, he was admitted to the hospital with chief complaints of abdominal pain, nausea, vomiting and one episode of fever for duration of 3 days. On admission, he was found to be hypotensive, and had hyperpnoea and supraventricular tachycardia. His dorsalis paedis artery and posterior tibial artery were not felt; however, his extremities were not cold and clammy. On admission, generalised abdominal tenderness, rigidity and guarding were noted. Immediately venous access in peripheral vein was taken and correction of arterial blood gas was performed.

After the correction of acidosis and hyponatraemia, the man immediately started receiving supportive medical management with vasopressin. Oxygen saturation was also corrected. On examination, serum ferritin levels were markedly raised, and vitamin D levels were found to be reduced. The CRP level and ESR were found to be 385 mg/L and 50, respectively. He also had remarkably increased serum amylase, serum lipase, serum LDH and triglycerides. Urinalysis showed high levels of creatinine and urea; however, serum calcium, albumin, globulins and total protein levels were reduced. The B-type natriuretic peptide level was found to be more than 35 000 ng/mL, and troponin T was also increased. The last known concentration of tacrolimus was 9 ng/mL. He then underwent haemodialysis. The X‑ray showed minimal left‑sided pneumothorax. The chest CT showed mild left pleural effusion with moderate right hydropneumothorax. Additionally, multiple ill‑defined patches of air space opacification with few air bronchograms were observed in bilateral lung fields, more marked in the right upper and lower lobes, which suggested multifocal consolidation. Additionally, few fibrotic bands were appreciated with multiple enlarged paratracheal, pretracheal, and subcarinal group of lymph nodes. Based on these findings, COVID-19 infection secondary to the mycophenolate mofetil and tacrolimus therapy was considered. However, the whole abdomen CT findings were unremarkable, which ruled out GI diagnosis. Bedside echo showed dilated right atrium and right ventricle with left ventricular ejection fraction of 60%. He also had mild-to-moderate tricuspid regurgitation with right atrial pressure of 30+. His immunosuppressive treatment with mycophenolate mofetil and tacrolimus was maintained at same dosages. Subsequently, the reverse transcriptase-polymerase chain reaction throat swab test for COVID-19 infection revealed negative results. On the next day, he was found to be afebrile and all the peripheral pulses were palpable. As a result, vasopressin was tapered; however, he again became hypotensive and showed supraventricular tachycardia. Therefore, the dose of vasopressin was again increased, and he was treated with ivabradine. On admission day 2, he had bilateral basal crepts with oedematous face and body. Therefore, he started receiving an off-label treatment with IV aztreonam 500mg injection, IV meropenem 1g injection and IV methylprednisolone 4mg injection. Additionally, he received symptomatic medical management. Subsequently, the doses of mycophenolate mofetil and tacrolimus were modified and changes in drug regimen were performed. The laboratory examination revealed underlying leucocytopenia. Therefore, he was treated with filgrastim. Subsequently, he underwent haemodialysis through right internal jugular vein. He developed nasal bleeding at night, which was managed with local packing of the nose. Despite all the treatment, he could not be revived and died [exact cause of death not stated]. At the time of death, the reverse transcriptase-polymerase chain reaction throat swab test for COVID-19 infection revealed negative results.