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 series of 2 cases, a 51-year-old man developed COVID-19 infection and nosocomial bacterial infection during treatment with ciclosporin and methylprednisolone, respectively and a 58-year-old man developed COVID-19 pneumonia and nosocomial bacterial infection during treatment with mycophenolate mofetil, methylprednisolone and unspecified steroid [routes and durations of treatments to reactions onsets not stated; not all dosages].

Case 1: A 51-year-old man was hospitalised on 14 February 2020 with a history of runny nose, fever and sore throat since 11 February 2020. In September 2018, he was diagnosed with acute myeloid leukaemia and underwent allogeneic bone marrow transplantation in June 2019. Following transplantation, he was receiving maintenance immunosuppressive therapy with ciclosporin [cyclosporine-A] and received regular follow-up every 3 months. On 20 January 2020, he travelled to a city in China for one day regular checkup and the result showed no relapse. On the trip, he denied the exposure to any confirmed case of COVID-19. On 11 February 2020 (22 days following exposure), he developed runny nose, a low grade fever and sore throat. A chest CT performed on 13 February 2020 revealed multiple patchy ground glass opacities bilaterally. On 14 February 2020 (day 3 of illness), a test for COVID-19 infection by real-time polymerase chain reaction assay was found to be positive. He was admitted to an isolation ward and received off-label treatment with oral lopinavir/ritonavir 200mg three times a day, immune globulin 10 g/day and methylprednisolone 40 mg/day. However, on 21 February.2020 (10 days following the fever onset), he developed severe shortness of breath. A repeat CT scan revealed the expansion of the lung lesions. He was administered oxygen via a nasal cannula, but his symptoms did not improve. The flow cytometry detection revealed low counts of T cells in the blood. On day 17, he was transferred to ICU and initiated on non-invasive ventilation. Ciclosporin was withdrawn, and he was administered antibiotics including moxifloxacin and unspecified cephalosporin, followed by linezolid, meropenem and caspofungin when nosocomial bacterial infection was confirmed by culture. In the following days, his situation deteriorated, and he was intubated for mechanical ventilation, but his hypoxaemia continued. Eventually, on 4 March 2020 (22 days following the onset of symptoms), he died due to respiratory failure.

Case 2: A 58-year-old man, who had a 12-year history of kidney transplantation, was hospitalised for 4 days of cough and fever on 30 January 2020. In 2008, he had undergone kidney transplantation due to end stage renal failure. Post-transplant, he was receiving immunosuppressive therapy with mycophenolate mofetil and unspecified steroid. Before the admission, the renal graft function was stable. He reported to have a positive contact with people from China on 1 January 2020. Seven days afterwards (on 26 January 2020), he experienced dry cough and a low grade fever. On the first day of illness, his CT scan was found to be normal. He received moxifloxacin and oseltamivir treatment for 4 days, but his symptoms did not ameliorate. He continued to have shortness of breath. A repeated CT scan showed typical signs of COVID-19 pneumonia. Off-label treatment with methylprednisolone 80 mg/day, lopinavir/ritonavir and high flow humidification oxygen inhalation therapy were initiated on day 4; but, his hypoxaemia continued worsening. On 3 February 2020, COVID-19 infection was confirmed with polymerase chain reaction. Also, nosocomial bacterial infection was observed. On 5 February 2020 (day 9 of admission), he was initiated on non-invasive ventilation, and on 16 February 2020 (day 20), mechanical ventilation was started. Later, on 19 February 2020 (on day 23), extracorporeal membrane oxygenation was initiated. The results of flow cytometry detection showed continuous low T cell count during the hospitalisation. Although, he was found to be negative for the coronavirus RNA detection after 25 February 2020 (day 29), he still developed multiorgan failure (heart, lung and kidney) and eventually died on day 40.