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Targeting IL-1, IL-6 or GM-CSF in COVID-19. Response to: ‘More evidences on which biologic and which pathway is key in severe-critical COVID-19 pneumonia’ by Ferraccioli
  1. Emanuel Della-Torre1,2,
  2. Corrado Campochiaro1,2,
  3. Giulio Cavalli1,2,
  4. Giacomo De Luca1,2,
  5. Fabio Ciceri2,3,
  6. Alberto Zangrillo2,4,
  7. Lorenzo Dagna1,2
  1. 1 Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy
  2. 2 Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy
  3. 3 Hematology and Bone Marrow Transplant Unit, San Raffaele Scientific Institute, Milan, Italy
  4. 4 Department of Anesthesia and Intensive Care, San Raffele Scientific Institute, Milan, Italy
  1. Correspondence to Dr Emanuel Della-Torre, Università Vita-Salute San Raffaele, San Raffaele Scientific Institute, Milan 20132, Italy; dellatorre.emanuel{at}

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We thank Prof Ferraccioli for his positive comments on our open-label trials with sarilumab, tocilizumab, anakinra and mavrilimumab in patients with severe hyperinflamed COVID-191–4 and for remarking the unprecedented opportunity offered by our studies to better understand the relative contribution of different targetable inflammatory pathways to the pathogenesis of severe COVID-19.5 The study designs we adopted should be definitely interpreted in light of the scientific data that progressively became available and of the course of the pandemic wave that struck Northern Italy and our Institution. Between 24 February and 22 May 2020, San Raffaele Hospital (Milan, Italy) admitted more than 1000 patients with COVID-19.6–8 Intriguingly, the clinical phenotype of admitted patients changed over time and the severity of the disease progressively varied in parallel with outbreak exhaustion.6

When our hospital was first hit by the pandemic, accumulating evidence from China was pointing at interleukin (IL)-6 as a master regulator of the cytokine storm occurring in severe COVID-19.9 Tocilizumab was, therefore, first used as a potential treatment2 and subsequently replaced by intravenous sarilumab due to sudden shortage of the drug.1 As described in …

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