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 case report, a 35-year-old man and a 45-year-old man were described, who developed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during immunosuppressive treatment with mycophenolate mofetil, prednisolone, tacrolimus and antithymocyte globulin. Both the patients additionally developed lymphopenia during immunosuppressive treatment with antithymocyte globulin [routes and times to reactions onsets not stated; not all dosages and outcomes stated].

Case 1 (a 35-year-old man): The man underwent living donor kidney transplant at a hospital in India on 20 March 2020. His medical history was significant for chronic kidney disease [unknown aetiology] and hypertension for the past 2 years, and he had been on haemodialysis for the duration of 12 months. He started receiving immunosuppressive treatment with mycophenolate mofetil, prednisolone and tacrolimus two days prior to the transplant, and on the day of the surgery (20 March 2020), he received induction agent antithymocyte globulin 1 mg/kg. By post-transplant day 3, his serum creatinine reached a nadir of 1 mg/dL, and he was discharged on post-transplant day 10. On post-transplant day 19, he developed dry cough; however, he was afebrile without shortness of breath. The laboratory findings revealed the following: BP 134/80mm Hg, RR 20 breaths/minute and oxygen saturation 99% in ambient air. The nasopharyngeal swab real-time reverse transcription polymerase chain reaction (rRT-PCR) test was found to be positive for SARS-CoV-2. Therefore, he was admitted to a hospital in India. On admission, the chest radiograph showed no abnormalities. Laboratory examination showed a total leucocyte count of 5.1 × 10⁹/L, absolute lymphocyte count of 0.4 × 10⁹/L, procalcitonin <0.05 ng/mL, CRP 10.8 mg/L, and blood culture revealed no growth. On admission, he started receiving an off-label treatment with azithromycin and hydroxychloroquine. Subsequently, immunosuppressive treatment with prednisolone was reduced to 15 mg/day and tacrolimus dose was adjusted to maintain a trough level of 4−6 ng/mL. He additionally developed lymphopenia secondary to the antithymocyte globulin therapy. Mycophenolate mofetil was then stopped. He additionally received an off-label treatment with valganciclovir 450 mg/day along with cotrimoxazole 80/400mg for SARS-CoV-2 infection; however, cotrimoxazole was subsequently reduced to alternate days. He remained afebrile throughout the course. On admission day 28, he was discharged with recommended home isolation. At discharge, his serum creatinine was found to be 1.05 mg/dL and nasopharyngeal swab rRT-PCR was still positive for SARS-CoV-2. He required no ICU monitoring and supplemental oxygen, and kidney allograft function remained stable throughout the course of COVID-19.

Case 2 (a 45-year-old man): The man, who had hepatitis-B and chronic kidney disease secondary to membranoproliferative glomerulonephritis, had been on haemodialysis for the past 3 years. On 23 March 2020, he underwent living donor kidney transplant at a hospital in India. He started receiving immunosuppressive treatment with mycophenolate mofetil, prednisolone and tacrolimus along with induction agent antithymocyte globulin 1 mg/kg. By post-transplant day 3, his serum creatinine reached a nadir of 1 mg/dL. On post-transplant day 7, he was found to be positive for SARS-CoV-2 infection during his indoor stay. At the time of diagnosis, he only had mild throat irritation. The laboratory findings revealed the following: BP 126/70mm Hg, RR 22 breaths/minute and oxygen saturation 98% in ambient air. At the time of diagnosis, chest radiograph showed no abnormalities and total leukocyte count was 10.9 ×1 0⁹/L with absolute lymphocyte count of 0.9 × 10⁹/L and serum procalcitonin was 0.06 ng/mL. The blood culture revealed negative results. He was then shifted to the COVID-19 ward and started receiving an off-label treatment with azithromycin and hydroxychloroquine. He additionally developed lymphopenia secondary to the antithymocyte globulin. The therapy with mycophenolate mofetil was consequently reduced to 250 mg/day. He additionally received an off-label treatment with valganciclovir 450 mg/day along with cotrimoxazole 80/400mg for SARS-CoV-2 infection. Later, cotrimoxazole was reduced to alternate days. He also underwent a rapid tapering of prednisolone to 15 mg/day and tacrolimus dose was adjusted to maintain a trough level of 4−6 ng/mL. After 48 days, his nasopharyngeal swab rRT-PCR test showed negative results. Therefore, he was discharged on admission day 52. At discharge, his serum creatinine was found to 0.9 mg/dL. He required no ICU monitoring and supplemental oxygen, and kidney allograft function remained stable throughout the course of COVID-19.