Mycophenolate mofetil/sirolimus

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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 62-year-old man developed COVID-19 infection and severe interstitial pneumonia during immunosuppressive treatment with sirolimus and mycophenolate mofetil [duration of treatments to reaction onsets not stated].

The man was admitted to an emergency department with a 3-day history of cough and fever on 04 March 2020. His history was significant for hepatitis C virus infection genotype 1 and non-alcoholic steatohepatitis (NASH)-related cirrhosis with hepatocellular carcinoma, for which he had undergone liver transplantation four years prior. He was overweight, and also had type 2 diabetes, arterial hypertension and dyslipidaemia. He had been receiving immunosuppressive treatment with sirolimus 1 mg/day and mycophenolate mofetil [not all dosages stated; routes not stated] along with other comedications. At admission, his body temperature was 38.5°C, HR was 92 /minute and BP was 125/70mm Hg. Laboratory investigations were as follows: CRP 18 mg/L, Hb 133 g/L, glucose 6.3 mM and leucocytes 5.1 G/L with increased levels of ALT. PCR showed positive results for SARS-CoV-2 infection, confirming diagnosis of COVID-19 infection secondary to the immunosuppressive treatment. Pulmonary low-dose CT scan showed bilateral sub-pleural ground-glass infiltrates. Arterial blood gas analysis revealed RR of 20 /min, oxygen saturation was 93%, decreased pO ₂ and bicarbonate levels.

The man was treated with off-label lopinavir/ritonavir 200/50mg twice a day and hydroxychloroquine 200mg twice a day. He also received empiric treatment with cefepime. The dose of sirolimus was decreased by 50% as there was risk of interaction with ritonavir, and sirolimus plasma levels were daily monitored to maintain them between 4−8 µg/L. His amlodipine and rosuvastatin treatments were discontinued. His fever persisted, and he experienced mild deterioration of respiratory function. His pO ₂ was 8.1 kPa, CRP levels were elevated and he experienced diarrhoea. Progression of the pulmonary infiltrates was confirmed on CT scan. Severe interstitial pneumonia was suspected, and cefepime was switched to meropenem. All blood cultures were found to be negative. During the next 3 days, his fever resolved, oxygen saturation increased and CRP level decreased. A significant improvement in his general condition was noted, and treatment with lopinavir/ritonavir and hydroxychloroquine was ceased. His clinical recovery continued. Sirolimus dose was increased back to 1 mg/day and the transaminase levels remained within the normal range.