Mycophenolate mofetil/ciclosporin/prednisolone

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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

In a study involving 7 paediatric patients with transplants treated between 13 February and 23 September 2020 in Iran, a 7-year-old boy and a 4.5-year-old boy were described, who developed COVID-19 infection during immunosuppressant therapy with mycophenolate mofetil, ciclosporin or prednisolone [routes, dosages and duration of treatments to reaction onsets not stated].

Case 1: A 7-year-old boy, who had Fanconi anaemia, underwent bone marrow transplantation on 24 February 2020. He was hospitalised following a 15 minute seizure associated with jaw locking. Following transplant, he started receiving immunosuppressant therapy with mycophenolate mofetil [Cellcept] and ciclosporin [cyclosporin]. Concurrently, he was started on folic acid and silymarin [Livergol]. He also developed graft versus host disease. His nasopharyngeal swab for SARS-CoV-2 was noted to be positive on real-time reverse transcription PCR, and he was admitted on 12 April 2020. On admission, ciclosporin was stopped, and he started receiving tacrolimus therapy. A regime of levetiracetam for seizure was prescribed. CT scan revealed evidence of ventriculomegaly. Due to delirium and restlessness, pyridoxine [vitamin B6] was commenced. MRI findings revealed subcortical lesions, cortical lesions and viral encephalitis pattern. A repeat MRI showed posterior reversible encephalopathy syndrome and meningoencephalitis. An increased urea and creatinine levels were noted. In the ICU, he was intubated due to ineffective respiration and loss of consciousness. His peripheral blood stream presumed haemolytic uraemic syndrome or thrombotic thrombocytopenic purpura. He started receiving off-label IV immune-globulin [IVIG] and hydroxychloroquine for COVID-19 infection. Subsequently, plasmapheresis was performed. A regime of dopamine, furosemide and dobutamine was administered for improvement of ejection fraction. He also underwent peritoneal dialysis. A lumbar puncture sample was noted to be normal; however, he remained unconscious. The Glasgow Coma Scale score was noted to be 3 out of 15, and his brain stem reflexes were lost. Eventually, he died due to cardiopulmonary arrest induced by COVID-19 encephalitis.

Case 2: A 4.5-year-old boy, who had X-linked lymphoproliferative disease, underwent bone marrow transplantation on 12 January 2020. He had been receiving immunosuppressant therapy with ciclosporin [cyclosporin] and prednisolone. He was also receiving voriconazole, ofloxacin, tranexamic acid and valganciclovir. He was admitted with food intolerance, vomiting and diarrhoea for 5 time. His nasopharyngeal swab for SARS-CoV-2 was noted to be positive on real-time reverse transcription PCR. Eventually, he was diagnosed with COVID-19 infection and started receiving off-label treatment with hydroxychloroquine, IV meropenem, oral oseltamivir, aciclovir [acyclovir], dexamethasone and vancomycin. He experienced worsening pulmonary infection, and developed bacterial superinfections in addition to COVID-19. Two months later, he died due to septic shock secondary to disseminated pulmonary infection.