Prednisolone/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 3-year-old boy developed COVID-19 infection during immunosuppression therapy with prednisolone and tacrolimus [routes and time to reactions onset not stated].

The boy was admitted in February 2020 because of dyspnoea. He had malaise, weakness, severe dry cough, tachypnoea, anorexia and respiratory distress for 4 days prior to the admission. He had a history of premature birth and liver cirrhosis due to biliary atresia. At the age of 18 months, he underwent a living donor partial organ liver transplant. Since then, he had been receiving immunosuppressive therapy with tacrolimus 2 mg/day and prednisolone 5 mg/day. During his previous admission, his mother mentioned upper respiratory tract infection 1 week prior, which did not improved with unspecified regular medical therapies. At presentation, he had tachypnoea and respiratory distress with decreased oxygen saturation. With the impression of acute respiratory distress syndrome (ARDS) he was admitted, and then was immediately transferred to ICU. Examination revealed heart rate of 110 /min, respiratory rate of 38−40 /min, oxygen saturation of 90−91% and normal BP. He was orient and alert with Glasgow coma scale (GCS) score of 15. His throat was congested with no tonsillar exudation. Lung auscultation revealed harsh breath sounds. Blood tests (on admission), revealed WBC count of 12.8 × 10³ /µL, lymphocyte count of 1024, neutrophil count of 10880 [units not stated], RBC count 4.6 × 10⁶ /µL, platelet count of 187 × 103 /µL, C-reactive protein (CRP) of 102 mg/dL, haemoglobin of 13.8 g/dL, erythrocyte sedimentation rate (ESR) of 56 mm/hour, potassium of 4.5 meq/L, sodium of 141 meq/L, magnesium 1.9 mg/dL, blood urea nitrogen (BUN) of 22.3 mg/dL, glucose of 88 mg/dL, creatinine of 0.6 mg/dL and lactate dehydrogenase (LDH) of 1277 U/L. Liver function profile revealed aspartate transaminase (AST) of 50 U/L, alanine transaminase (ALT) of 28 U/L, albumin of 2.7 g/dL, alkaline phosphatase (Alk-ph) of 162 U/L, prothrombin time (PT) of 16 seconds, international normalized ratio (INR) of 1.7 and partial thromboplastin time (PTT) of 28 seconds. From the first day of admission, he was started on meropenem, vancomycin, voriconazole, azithromycin and cotrimoxazole. After 48 hours of hospitalisation, he became unresponsive to continuous positive airway pressure (CPAP). Hence, he was intubated.

The boy's tacrolimus and prednisolone treatment was stopped. On day 3 of admission, his liver enzymes increased. He also developed acute kidney injury with increase in creatinine and BUN. Blood cultures were negative. Chest X-ray onadmission demonstrated bilateral infiltration, but on day 4, it became a white lung. Due to suspicion of COVID-19, he was started on off-label treatment with hydroxychloroquine 15 mg/day, oseltamivir 30 mg/day and lopinavir/ritonavir 100 mg/day. Real time polymerase chain reaction (RT-PCR) of nasopharyngeal swab for COVID-19 was positive. During his hospital course, he developed multi-organ failure including liver failure, kidney failure and heart failure. On day 6 of the admission, he had excessive bleeding from mouth and nose, following which he had cardiorespiratory arrest. After 45 minutes of cardiopulomary resuscitation (CPR), he died on day 6 of admission. Laboratory test performed on day 5 revealed WBC count of 10.8 × 10³ /µL, lymphocyte count of 702, neutrophil count of 9190 [units not stated], RBC count 4.6 × 10⁶ /µL, platelet count of 165 × 10³ /µL, haemoglobin of 10.8 g/dL, ESR of 61 mm/hour, potassium of 5.1 meq/L, sodium of 146 meq/L, magnesium 2.8 mg/dL, BUN of 92 mg/dL, glucose of 114 mg/dL, creatinine of 2.3 mg/dL, AST of 3000 U/L, ALT of 4000 U/L, albumin of 3.3 g/dL, Alk-ph of 160 U/L, PT of 16 seconds, INR of 1.7 and PTT of 28 seconds.