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 67-year-old woman developed COVID-19-induced acute hypoxic respiratory failure, and community acquired pneumonia during treatment with mycophenolate mofetil and tacrolimus as immunosuppressant agent.

The woman presented to University Medical Center (UMC) with worsening shortness of breath. She had undergone cardiac transplant 1 year prior to the presentation. At the time of presentation, she was on immunosuppressant regimen including mycophenolate mofetil 250mg twice daily and tacrolimus 9mg daily [routes not stated]. Her symptoms of fever, headaches and myalgias had started 6 days prior to the presentation. Two days after the symptoms onset, she visited a clinic and diagnosed with COVID-19. At that time, she was pauci-symptomatic and was sent home with over the counter medications [specific drugs not stated]. On the day of admission to UMC (current presentation), her symptoms of cough and dyspnoea worsened acutely. Her dyspnoea had become so severe that she was unable to walk. In the emergency room, she was found to be dyspnoeic at rest requiring 4–5 L/minute nasal cannula to maintain saturations >90%. Her physical examination was unremarkable except 'mildly distant heart sounds, and globally diminished breath sounds. Leukopaenia and lymphocytopenia was noted along with elevated creatinine level. She was also found to have elevated inflammatory markers and mild elevation in D-dimer level.

The woman was started on a prophylactic dose of enoxaparin sodium [enoxaparin]. A repeat testing confirmed COVID-19 infection. Chest X-ray revealed new increased density in the right lower lung concerning for infiltrate as well as central vascular prominence. Chest CT showed diffuse peripheral and lower lung predominant ground-glass opacities, with some underlying septal thickening. Transthoracic echocardiogram revealed a normal left ventricular ejection fraction 55–60% and normal right ventricular systolic function. Brain natriuretic peptide (BNP) was elevated. Blood and respiratory cultures showed no growth through out her admission. In view of her history of heart transplant and concern for progression of her acute hypoxic respiratory failure, she was admitted to the coronary care unit. She was started on off label treatment with convalescent-anti-SARS-CoV-2-plasma [convalescent plasma] for COVID-19 infection along with dexamethasone. Additionally, she was started on unspecified empiric antibiotics for suspected community-acquired pneumonia. Clinically, she appeared dehydrated therefore, maintenance fluids were administered and consequently, her renal function back to baseline; renal disorder recovered. The following day, she was started on a 5 day course of remdesivir and her mycophenolate mofetil was stopped. Tacrolimus trough level was found to be supra-therapeutic, so it was also discontinued. Throughout the course of her admission, her renal function improved and her tacrolimus levels were adjusted to 6–10 ng/mL. Her leukopaenia resolved; however, she continued to have a persistent lymphocytopenia consistent with her COVID-19 infection. Inflammatory markers level decreased. She completed her courses of remdesivir and empiric antibiotics. Repeat chest X-ray revealed a significant improvement. She was discharged home with instructions to complete 20 days of isolation. Additionally, she was instructed to follow-up with her transplant physicians to discuss resuming her mycophenolate mofetil therapy. She was discharged with dexamethasone and tacrolimus extended release.