Ciclosporin/methylprednisolone/tocilizumab

A 61-year-old man developed COVID-19 pneumonia during treatment with ciclosporin and methylprednisolone. Additionally, he developed leukopenia and neutropenia during off label treatment with tocilizumab for COVID-19 pneumonia [not all routes stated; duration of treatments to reactions onsets not stated].

The man had undergone kidney transplantation from a deceased donor in 2005 for end-stage renal disease due to chronic interstitial nephritis. Later, he was admitted for shivering and persistent fever for over 48 hours. He had chronic kidney disease stage IIIa and was on maintenance immunosuppression with ciclosporin [cyclosporine A] and oral methylprednisolone. At first examination, peripheral capillary oxygen saturation was 97% breathing ambient air, BP was 136/72mm Hg and body temperature was 38°C. Laboratory blood tests were normal with minimally elevated C-reactive protein, mild acute kidney injury. Chest radiography showed minimal left pleural effusion. Urinary cultures showed urinary tract infection and he started receiving meropenem. On day 3 after admission, SARS-CoV-2 infection was suspected because of the negativity of urinary cultures and serum procalcitonin and persistence of fever. Then, he was isolated in a single room. Treatment with meropenem was stopped, oropharyngeal/nasal swab for SARS-CoV-2 was performed. He was found to have bilateral basal interstitial pneumonia in chest radiograph, arterial blood gases were unremarkable partial pressure of oxygen (pO₂) was 91mm Hg breathing ambient air. A third attempt for SARS-CoV-2 test on day 9 after admission test was found positive, and COVID-19 pneumonia was confirmed. On the day of COVID-19 diagnosis, his arterial pO₂ dropped to 57mm Hg and low-flow oxygen through nasal cannula. He then started receiving hydroxychloroquine 200mg twice daily and ciclosporin dose was reduced by a half. Additionally, he was started on unspecified IV fluids. Laboratory exams showed lymphopenia and leukopenia. After 2 days, due to lack of improvement in his clinical conditions, ciclosporin was stopped and oral methylprednisolone dose was increased to 16 mg/day. Subsequently, off label treatment with SC tocilizumab 324mg was also started. His interleukin-6 (IL-6) levels in blood were found to be high (280.86 pg/mL). He developed progressive leukopenia. Under suspicion of tocilizumab-related leukopenia (leukocyte nadir at 660 /μL) with neutropenia (neutrophils 400 /μL), and to enhance anti-inflammatory and immunomodulatory response, he was treated with IV immunoglobulin (IVIG) 0.3 g/kg. His leukocyte count increased to 2090 /μL (lymphocytes 670 /μL and neutrophils 1180 /μL) and CD4 count to 518 /μL. On day 14 after hospitalisation, urinary culture showed positive for multiresistant Pseudomonas aeruginosa, and antibiotic treatment with meropenem was restarted. On the same day, chest radiograph revealed multiple nonhomogeneous bilateral consolidations, and oral azithromycin was started for 3 days for preventing bacterial superinfection. The radiographic imaging showed evolution of COVID-19 pneumonia. Since tocilizumab administration, he remained to be apyretic. A progressive improvement was noted in his arterial pO₂ levels always above 60mm Hg and oxygen treatment was stopped. The level of IL-6 also increased to 619.11 pg/mL as expected, 6 days after receiving tocilizumab.

The man was discharged home on day 22 with no fever. At that time, his peripheral oxygen saturation was 95% breathing ambient air, WBC was 2970 /μL, respiratory frequency was 14 acts/minute and BP was 140/80mm Hg. Oropharyngeal/nasal swab for SARS-Cov-2 still showed positive at day 13 after diagnosis. He was suggested appropriate isolation measures at home. The treatment with hydroxychloroquine was stopped 13 day after its initiation, and ciclosporin was still withheld.