Leukemia | 2021
Siltuximab downregulates interleukin-8 and pentraxin 3 to improve ventilatory status and survival in severe COVID-19
Abstract
Severe coronavirus disease 2019 (COVID-19) is characterized by interstitial pneumonia/acute respiratory distress syndrome and hyperinflammation, with elevated levels of proinflammatory cytokines, such as interleukin-6 (IL-6), associated with mortality and patients requiring ventilator support [1–3]. Targeting the IL-6 signaling pathway has been identified as a potential strategy to mitigate the elevated cytokines and resulting hyperinflammation associated with COVID-19 [1]. Siltuximab is the first and only US Food and Drug Administrationand European Medicines Agency-approved monoclonal antibody that specifically binds to IL-6, thereby inactivating IL-6–induced signaling. Siltuximab is currently approved for the treatment of adults with idiopathic multicentric Castleman disease [4]. The aim of this study was to examine the association between siltuximab treatment, serum cytokine and chemokine levels, and mortality and/or respiratory function in hospitalized patients with COVID-19 and acute respiratory distress syndrome. We designed a prospective, observational cohort study at the start of the pandemic in response to the urgent unmet need for an effective treatment for patients with SARS-CoV-2 pneumonia, hyperinflammation, and respiratory failure [5]. In accordance with clinical guidelines developed at the Papa Giovanni XXIII Hospital in Bergamo, Italy, siltuximab was initially supplied under a compassionate-use program for the emergency treatment of 30 patients with severe COVID-19 requiring ventilatory support. Consequently, an investigator-initiated study protocol was developed for immediate implementation. The study protocol was submitted and approved through the Hospital Ethics Board. Patients, or