Abstract: Leukemia (2021) 35:2710–2714
https://doi.org/10.1038/s41375-021-01299-x
LETTER
INFECTIOUS MEDICINE, VIROLOGY
Siltuximab downregulates interleukin-8 and pentraxin 3 to improve
ventilatory status and survival in severe COVID-19
Giuseppe Gritti 1 Federico Raimondi2,3 Barbara Bottazzi4 Diego Ripamonti5 Ivano Riva6 Francesco Landi1,7
Leonardo Alborghetti5 Marco Frigeni1 Marianna Damiani6,8 Caterina Micò1 Stefano Fagiuoli9
Ferdinando Luca Lorini6 Lucia Gandini6,8 Luca Novelli 2 Jonathan P. Morgan10 Benjamin M. J. Owens10
Karan J. K. Kanhai10 Gordana Tonkovic Reljanovic11 Marco Rizzi5 Fabiano Di Marco 2,12
Alberto Mantovani3,13,14 Alessandro Rambaldi 1,15
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Received: 1 April 2021 / Accepted: 12 May 2021 / Published online: 24 May 2021
© The Author(s) 2021. This article is published with open access
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To the Editor:
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 Administration- and European Medicines
Agency-approved monoclonal antibody that specifically
binds to IL-6, thereby inactivating IL-6–induced signaling.
Supplementary information The online version contains
supplementary material available at https://doi.org/10.1038/s41375021-01299-x.
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
* Giuseppe Gritti
g.gritti@asst-pg23.it
8
Postgraduate School of Anesthesiology and Intensive Care,
University of Milan, Milan, Italy
1
Hematology Unit, Azienda Socio Sanitario Territoriale Papa
Giovanni XXIII, Bergamo, Italy
9
Gastroenterology Unit, Azienda Socio Sanitario Territoriale Papa
Giovanni XXIII, Bergamo, Italy
2
Pneumology Unit, Azienda Socio Sanitario Territoriale Papa
Giovanni XXIII, Bergamo, Italy
10
EUSA Pharma, Hemel Hempstead, UK
11
ErgoMed PLC, Guildford, UK
Postgraduate School of Respiratory Medicine, University of
Milan, Milan, Italy
12
Department of Health Sciences, University of Milan, Milan, Italy
13
Department of Biomedical Sciences, Humanitas University,
Milan,..
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{ 'value': 'JPM, BMJO, and KJKK are employees of EUSA Pharma. AR reports consultancy fees '
'from Amgen, Celgene, Gilead, Italfarmaco, Novartis, Omeros, Pfizer, and Roche; '
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