The role of ibrutinib in COVID-19 hyperinflammation: a case
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Immune modulation in COVID-19 is emerging as an important therapeutic strategy as increasing evidence suggests that inflammatory pathways are implicated in lung damage. Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, are commonly used to treat indolent B-cell neoplasms and chronic graft-versus-host disease (GvHD).

Authors describe an 81 year-old male receiving ibrutinib for Waldenstrom macroglobulinaemia (WM) who was hospitalized with COVID-19. WM is a relatively indolent lymphoproliferative disorder characterized by IgM monoclonal gammopathy and lymphoplasmacytic infiltrate in the bone marrow. On stopping the BTKi due to concerns of additional immunosuppression, he required non-invasive ventilation (NIV) in the intensive care unit (ICU) and demonstrated prompt clinical recovery when ibrutinib was reinstated.

On admission, the patient described a one-week history of nausea, fever and dry cough with c-reactive protein (CRP) 73.4mg/l and was commenced on intravenous (IV) piperacillin-tazobactam. COVID swab RT-PCR at admission was positive. His observations were stable, he did not require additional oxygen and blood tests and chest x-ray (CXR) were unremarkable. Five days later, 11 days since symptoms onset, he became pyrexial at 38oC, CRP had increased to 136mg/l and he was commenced on oral azithromycin and once daily
dexamethasone 8mg.

Repeat CXR showed new pulmonary opacities but he remained clinically stable with no oxygen requirement. Ibrutinib was withheld from day 6 of admission. CRP improved to 76 mg/L in accordance with the introduction of steroids. Forty-four hours following the last dose of BTKi he developed a new, rapidly increasing, oxygen requirement and within 8 hours he was admitted to ICU for NIV to achieve adequate oxygenation (day 7 of admission, 13 days since symptoms onset). Within 24 hours of ITU admission, his BTKi was reinstated at full dose 420mg and remdesivir was commenced.

A briefrise and subsequent fall in CRP was observed to follow the pattern of events(see figure A). After only 14 hours of NIV (initial requirements of PEEP 8 and FiO2 55) his oxygen requirements decreased and the following day he was stepped down to the ward on 4L O2 via nasal cannula. He continued to improve and at 19 days after admission (day 25 of symptoms onset) he was medically fit for discharge with no supplementary oxygen requirement.

Dr. R●●●●v J●●●i
Dr. R●●●●v J●●●i Internal Medicine
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