Antithymocyte-globulin

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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 woman in her 20s developed worsening of SARS-CoV-2 infection during treatment with antithymocyte-globulin for acute rejection in heart transplantation.

The woman had undergone successful heart transplantation (HT) for giant-cell myocarditis in November 2018 at the age of 22 years. At that time, she had received immunosuppressive therapy with antithymocyte-globulin [rabbit anti-thymocyte globulin; rATG], tacrolimus, mycophenolate mofetil, methylprednisolone and prednisone. In December 2019, she presented with a sub-diaphragmatic mass around the inferior vena cava and pericardial constriction. She underwent pericardectomy. Biopsy of sub-diaphragmatic mass showed an Ebstein‒Barr virus-induced lymphoma. At that time, she was receiving tacrolimus, mycophenolate mofetil and prednisone. Lymphoma was treated with decrease in immunosuppression and rituximab. She was admitted again in March 2020 due to vomiting and abdominal pain. Her tracheal and nasal swab polymerase chain reaction (PCR) were positive for SARS-CoV-2 infection. Her chest CT scan revealed a right-sided pleural effusion. She also exhibited severe biventricular dysfunction. Acute humoral rejection was excluded following endomyocardial biopsy. Her allograft function worsensed continuously. Therefore, acute rejection was suspected. At that time she was receiving mycophenolic-acid, tacrolimus and prednisone. Thereafter, she additionally started receiving treatment with IV antithymocyte-globulin 1.5 mg/kg daily for 3 days and methylprednisolone. After a short duration, a CT scan revealed the onset of a severe pulmonary COVID-19 infection, which was attributed to antithymocyte-globulin mediated worsening of SARS-CoV-2 infection [duration of treatment to reaction onset not stated].

The woman was treated with an off-label lopinavir/ritonavir therapy every 12 hours for 14 days for COVID-19 infection. Despite these treatments, her condition deteriorated, and she required venoarterial extracorporeal membrane oxygenation support. She was extubated 16 days later as the pulmonary insult alleviated. However, no cardiac recovery was noted. Therefore, she compassionately registered on the waitlist for an emergent HT. At that time, her nasal swab was PCR positive. She then underwent heart retransplantation. Her heart retransplantation was uneventful. A week later, she was extubated. On the day of ICU discharge, she had a normal chest X-ray; but she was still positive for SARS-CoV-2 PCR. After rehabilitation at post-operative day 44, she was discharged home; however, she was still PCR positive. Histologic examination of the former graft showed a chronic rejection process. Her SARS-CoV-2 serology tests were negative during the entire hospital stay and viral loads were not measured.