Immunosuppressants/rituximab

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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 report, two women (a 62-year-old and a 56-year-old) were described, who developed coronavirus disease 2019 (COVID-19) pneumonia during immunosuppressive treatment with prednisone, ciclosporin, azathioprine, tacrolimus, everolimus or rituximab [dosages and routes not stated; duration of treatments to reactions onset not clearly stated].

Patient 1: The 62-year-old woman had undergone bilateral lung transplant due to tobacco induced end-stage emphysema in November 2016. Her postoperative course was uneventful. Subsequently, she started receiving immunosuppressive treatment with prednisone, ciclosporin [cyclosporine] and azathioprine. Over the years her immunosuppressive treatment was adjusted to prednisone, azathioprine, everolimus and tacrolimus. Approximately 3.5 years following the transplantation in 2020, she presented to her primary care physician after exposure to various family members who tested positive for COVID-19. Her symptoms included rhinorrhea, chills and a mild dry cough. A nasopharyngeal swab revealed positive result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. After two days, she was hospitalised with shortness of breath, fevers and hypoxia, which required nasal cannula supplementation. It was reported that two months prior to diagnosis of COVID-19, pulmonary function test showed a forced expiratory volume at 1 second of 2.5L (112% predicted) and a forced vital capacity of 2.8L (95% predicted). She was treated with a 5 day course of remdesivir and off label treatment with dexamethasone 6mg for 10 day. She was weaned to room air, and discharged on sixth day of hospitalisation. Five days following the discharge, she was again hospitalised due to recurrent fevers and chills. Oxygen saturation was 84% on room air with chest radiograph showed new bilateral multifocal patchy opacities. Her oxygenation and work of breathing deteriorated continuously. Therefore, she was intubated on second day of hospitalisation. She received an empiric treatment with vancomycin and cefepime. She was paralyzed and proned on third day of hospitalisation with only short-term improvement in oxygenation levels during proning episodes. Also, she was administered with high-dose of unspecified pulse steroids for empiric treatment of acute allograft rejection. She developed acute renal failure and haemodialysis was initiated on fifth day of hospitalisation. On day 16 of hospitalisation, extubation was attempted; however, later that day she required reintubation. On day 19 of hospitalisation, she underwent tracheostomy and gastrostomy tube placement. Over the subsequent weeks, she tolerated a ventilator wean, and was eventually decannulated on day 38 of hospitalisation. Prior to returning home, she was discharged to an acute rehabilitation facility. Based on these findings and clinical presentation, it was concluded that she developed COVID-19 pneumonia, which might have associated with immunosuppressive treatments.

Patient 2: The 56-year-old woman had undergone bilateral lung transplant due to interstitial lung disease and secondary pulmonary hypertension in September 2014. Her postoperative course was complicated by atrial tachyarrhythmias, reintubation and delirium. Subsequently, she started receiving immunosuppressive treatment with prednisone, ciclosporin [cyclosporine] and azathioprine. Several months later, she developed post-transplant lymphoproliferative disorder which was treated with rituximab, and azathioprine was discontinued. Over the successive years, her pulmonary function continuously declined. Eventually, she was diagnosed with grade 3 restrictive chronic lung allograft dysfunction, which required 4 L/min nasal cannula at rest and 8 L/min with exertion. Approximately 5.5 years after transplant in 2020, she presented to the emergency department with fevers, cough and shortness of breath after close contact with family members who tested positive for COVID-19. To maintain adequate saturations, she required 8 L/min oxygen. Chest radiograph showed an ill defined hazy opacity over the left lung. A nasopharyngeal swab revealed positive result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. She was treated with remdesivir and empiric cefepime. Subsequently, she was weaned to 4 L/min nasal cannula at rest and 10 L/min with exertion. On sixth day of hospitalisation, she was discharged. It was reported that pulmonary function test 1 month prior to infection showed a forced expiratory volume at 1 second of 1.1L (43% predicted) and forced vital capacity of 1.3L (42% predicted). Three days after discharge, she was again hospitalised due to deteriorating hypoxia and work of breathing. Repeat chest radiograph showed slightly deteriorating pulmonary opacities. She was treated with vancomycin, azithromycin, meropenem as well as unspecified high-dose steroids for empiric treatment of acute allograft rejection. She had refused to be intubated and was transitioned to comfort care. Based on these findings and clinical presentation it was concluded that she developed COVID-19 pneumonia, which might have associated with immunosuppressive treatments. Eventually, she died on third day of hospitalisation [cause of death not stated].