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

A 50-year-old man developed coronavirus disease-2019 (COVID-19) during immunosuppressive treatment with antithymocyte globulin, everolimus, unspecified steroids, prednisone and tacrolimus [routes, time to reaction onset and outcome not stated; not all dosages stated].

The man was admitted to the emergency room (ER) due to a 24h history of fever and vomiting on 28 February. He did not report any other symptoms. He had undergone third kidney transplantation in 2016 and received induction immunosuppression with antithymocyte globulin [thymoglobulin], everolimus, unspecified steroids and tacrolimus. Further, his immunosuppression was maintained with tacrolimus, everolimus and prednisone 5mg once a day. Concurrently, he was on losartan for arterial hypertension. Due to signs of mild dehydration, he was treated with oral hydration and eventually discharged with a presumptive diagnosis of non-severe viral gastroenteritis with paracetamol. Five days later, he returned to the ER with persistent fever and productive cough without GI symptoms. Physical examination demonstrated a body temperature 37.4°C, BP 180/100mm Hg, pulse 66 beats/minute, RR 16 breaths/minute and blood oxygen saturation 98% on room air. He also had signs of mucous dehydration and crackles in the right lower lung along with signs of left eye conjunctivitis. Heart examination did not describe murmurs, rubs or gallops. Laboratory findings showed WBC count 10.15 × 10⁹/L (total lymphocyte count 1.8 × 10⁹ U/L), platelet count of 126 × 10⁹/L and CRP level 13.2 mg/dL. Posteroanterior chest X-ray revealed a medium lobe consolidation. A community-acquired pneumonia was presumed. He started receiving empiric therapy with ceftriaxone and azithromycin. Testing of nasopharyngeal and oropharyngeal swab specimens for SARS-CoV-2 by real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assays were positive (day 0). A diagnosis of COVID-19 infection secondary to immunosuppressive therapy was confirmed.

The man was hospitalised under isolation and started receiving off-label therapy with oral solution of lopinavir/ritonavir 400/100mg twice a day on day 1. Due to the interaction of ritonavir and tacrolimus, his tacrolimus therapy was stopped. Everolimus was also discontinued due to the risk for mTOR-inhibitor induced pneumonitis. He also received empiric broad spectrum antibiotics. Further, oral off-label therapy with hydroxychloroquine 400mg twice a day for 24h and afterwards 200mg twice a day was initiated. After 10 days from the initial symptoms and 72h after the off-label anti-viral therapies, he exhibited a worsening in respiratory symptoms with hypoxia despite the use of high-flux nasal oxygen delivery, and he was diagnosed with respiratory failure. He received norepinephrine. Chest X-ray showed a progression to diffuse bilateral infiltrates. Off-label therapy with SC interferon-β 250µg every 48h was started. On day 6, he was intubated with ventilatory supportive care using high positive end-respiratory pressure (PEEP) was provided. On day 12, he remained in ICU under respiratory supportive therapy without further progression of respiratory failure.