Tocilizumab therapy in 5 solid and composite tissue transplant recipients with early ARDS due to SARS-CoV-2.
Jose A MorillisFrancisco Marco CanosaPavithra SrinivasTannaz AsadiCassandra CalabresePrabalini RajendramMarie BudevEmilio D PoggioK V Narayanan MenonBrian GastmanChristine KovalPublished in: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (2020)
There are emerging data depicting the clinical presentation of coronavirus disease 19 (COVID-19) in solid organ transplant recipients but negligible data-driven guidance on clinical management. A biphasic course has been described in some infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), beginning with a flu-like illness followed by an intense inflammatory response characterized by elevated c-reactive protein (CRP), interleukin 6 (IL-6), and acute respiratory distress syndrome (ARDS) associated with high mortality. The exuberant and possibly dysregulated immune response has prompted interest in therapeutic agents that target the cytokines involved, particularly IL-6. Tocilizumab is an IL-6 receptor antagonist with a record of use for a variety of rheumatologic conditions and cytokine release syndrome due to chimeric antigen receptor T-cell therapy but experience in solid organ and composite tissue transplant recipients (SOT/CTTRs) with SARS-CoV-2-related ARDS has not been previously reported in detail. We present the clinical course of 5 SOT/CTTRs with SARS-CoV-2-related ARDS that received tocilizumab with favorable short-term outcomes in 4. Responses were characterized by reductions in CRP, discontinuation of vasopressors, improved oxygenation and respiratory mechanics, and variable duration of ventilator support. Four bacterial infections occurred within 2 weeks of tocilizumab administration. We discuss safety concerns and the need for randomized comparative trials to delineate tocilizumab's clinical utility in this population.
Keyphrases
- acute respiratory distress syndrome
- sars cov
- respiratory syndrome coronavirus
- rheumatoid arthritis
- extracorporeal membrane oxygenation
- coronavirus disease
- juvenile idiopathic arthritis
- mechanical ventilation
- cell therapy
- rheumatoid arthritis patients
- inflammatory response
- immune response
- disease activity
- stem cells
- double blind
- placebo controlled
- open label
- case report
- phase iii
- clinical trial
- coronary artery disease
- dendritic cells
- preterm birth
- machine learning
- study protocol
- data analysis
- deep learning
- blood flow