Mycophenolate-mofetil/prednisone/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 39-year-old man developed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) during treatment with mycophenolate mofetil, prednisone and tacrolimus as immunosupression therapy [routes not stated; not all dosages stated].

The man with a history of idiopathic dilated cardiomyopathy and chronic kidney disease, and underwent combined heart/kidney transplant in 2017, presented for COVID-19 testing. He had symptoms of fever, headache, dyspnoea, fatigue, sore throat, dry cough and myalgia. On the nest day of the testing, he was found positive for COVID-19. As the symptoms were minimal, he was quarantined at his home. On the next day, his symptoms worsened. Therefore, he was advised to return to the hospital for further evaluation. Previously, he had antibody-mediated cardiac graft rejection, which was being treated with methylprednisolone, plasmapheresis, IV immunoglobulin [Gamunex] and antithymocyte-globulin [rabbit anti-thymocyte globulin]. He had completed this treatment approximately 8 months prior to the admission. His history was significant for poorly controlled insulin-dependent diabetes mellitus, morbid obesity, hypertension and chronic diabetic foot ulcers. Upon his repeat presentation, he had headache, fatigue and dyspnoea. He was afebrile, normotensive and mildly tachycardic. Oxygen saturation was of 97% on room air. Another nasopharyngeal swab also found positive for COVID-19. Laboratory test showed elevated levels of C-reactive protein, serum lactate, D-dimer, lactate dehydrogenase and troponin I. Chest x-ray (CXR) showed mild pulmonary vascular congestion. Therefore, he was admitted for monitoring and supportive care. Upon admission, his mycophenolate mofetil was held due to his pronounced lymphopenia. However, his treatment with tacrolimus, losartan and prednisone 9mg daily kept continued. On the following day, he remained afebrile with minimal dyspnoea upon exertion. He was discharged as he insisted to. He was advised to continue holding mycophenolate mofetil until further notice. After three days, he was readmitted due to worsening of symptoms with hypoxia. At admission, he was treated with paracetamol, and he became afebrile. He was normotensive, tachycardic and tachypneic with an oxygen saturation of 95% on room air. His D-dimer, LDH, CRP, BNP and troponin I levels were found to be elevated. Therefore, his tacrolimus doses were adjusted to tacrolimus trough level of 5-8 ng/mL. A severely low immune cell response was noted upon examination. His treatment with tacrolimus and prednisone were continued, while his losartan and mycophenolate mofetil remained held. He was started on off label hydroxychloroquine 400mg twice daily. On the next day, he developed low-grade fever with hypoxia, which required 4 lpm of oxygen via nasal cannula. Due to rapid respiratory decompensation, he was shifted to the ICU. He was enrolled in the Adaptive COVID-19 Treatment Trial (NCT04280705) evaluating remdesivir versus placebo and started on the study drug. His treatment with hydroxychloroquine was discontinued. He had mild fever and chills over the next two days, which were controlled with aspirin. His oxygen requirements decreased steadily. A left ventricular ejection fraction was found to be normal upon transthoracic echocardiography. Therefore, he was shifted to the general ward. He was slowly weaned off oxygen supplementation. Eventually, he was discharged.