Immunosuppressants

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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 men (a 46-year-old man and a 71-year-old man) were described, who developed coronavirus disease 2019 (COVID-19) pneumonia during immunosuppression therapy with ciclosporin, methylprednisolone, mycophenolate-mofetil, tacrolimus or unspecified corticosteroids [routes, dosages, duration of treatments to reactions onset not stated].

Case 1: A 46-year-old man developed COVID-19 pneumonia during immunosuppression therapy with tacrolimus, mycophenolate-mofetil and unspecified corticosteroids. The man had undergone bilateral lung transplant due to cystic fibrosis in April 2011 and discharged on immunosuppressive therapy with mycophenolate mofetil, ciclosporin and unspecified corticosteroids. Thereafter, he developed renal failure in 2015 that required dialysis in 2019. His immunosuppression therapy with ciclosporin changed to tacrolimus in March 2017. On 14 March 2020, he developed hyperpyrexia. He started receiving antibacterial therapy with teicoplanin for 3 weeks. Additionally, enoxaparin sodium [enoxaparin] was also prescribed due to thrombosis related to possible infection of the arteriovenous fistula and mycophenolate mofetil was stopped. Two days later, his nasopharyngeal swab showed positive result for SARS-CoV-2 RNA, and he was admitted to the hospital. At the admission, he was well oriented and alert with normal breathing and O₂ saturation of 99% in ambient air. He had catheter placed in the right jugular vein. Chest x-ray revealed ground-glass opacities at the bases of his both lungs with left-sided pulmonary thickening. His lab test showed elevation in the inflammation markers, thrombocytopenia at 56 × 10⁹ cells/L and elevated D-dimer levels. On day 4, his CT scan demonstrated many ground-glass opacities in the peripheral area of his lung lobes and several peribronchovasal consolidations with confluent aspect to basal parts of lower lobe of left lung with notes of air bronchogram. The catheter was removed and teicoplanin was discontinued as precautionary measures. It was also suspected that teicoplanin contributed to fever and pancytopenia. He had concurrent bacterial superinfection, for which meropenem and tigecycline were initiated. During the admission, he continued receiving enoxaparin sodium and dialysis. Thereafter, he was discharged in good condition without fever or cough and a clear chest radiograph. At the time of discharge, he was taking tacrolimus 0.5mg twice a day and unspecified corticosteroids 7.5 mg/day. At the time of discharge and 72 hours after the discharge, his nasopharyngeal swabs still showed positive results for SARS-CoV-2 RNA. He also had mild diarrhea, and his stools test showed positive results for SARS-CoV-2. Later, on day 37 after onset of the symptoms, his nasopharyngeal swab and stools test showed negative results for SARS-CoV-2.

Case 2: A 71-year-old man developed COVID-19 pneumonia during immunosuppression therapy with ciclosporin, tacrolimus, mycophenolate-mofetil and methylprednisolone. The man had undergone bilateral lung transplantation for chronic obstructive pulmonary disease in June 2011 and discharged on immunosuppressive therapy with mycophenolate mofetil, ciclosporin and methylprednisolone. He was also receiving tacrolimus. He had diabetes, progressive chronic renal failure, hypertension, osteoporosis, acute pancreatitis and increased body weight. Additionally, he was receiving insulin, furosemide and verapamil concomitantly. On 7 March 2020, he developed hyperpyrexia, dyspnoea, cough and diffuse arthralgia. Initially, he started on off label treatment with azithromycin without resolution of his symptoms. On day 6 after onset of the symptoms, his sputum showed positive result for SARS-CoV-2 infection and a chest X-ray revealed bilateral interstitial pneumonia without pleural effusion. Due to continuous decrease in the O₂ saturation, he was admitted to the hospital and diagnosed with acute respiratory distress with COVID-19 pneumonia. His laboratory test results showed normal lymphocyte and WBC counts, a substantial decrease in the neutrophils and increase in the CRP and D-dimer levels. He underwent a CT scan that showed diffuse ground-glass opacities with several consolidations mainly in the right lung and diffused interstitial involvement in all the lobes. His mycophenolate-mofetil, tacrolimus and ciclosporin were suspended. But, methylprednisolone 40mg twice a day with slow tapering was continued. Anticoagulation therapy with enoxaparin sodium [enoxaparin] was initiated, and he was placed in prone position. Mechanical ventilation was provided, and he received off label treatment with lopinavir/ritonavir, piperacillin/tazobactam, hydroxychloroquine and aciclovir for COVID-19 pneumonia. Subsequently, he had deterioration of gas exchanges along with progressive worsening of lymphocyte counts and neutrophilia. His condition irremediably deteriorated, and he died due to COVID-19 pneumonia on day 27 after onset of initial symptom.