Article Text

Download PDFPDF

Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin
  1. Alessia Alunno1,
  2. Francesco Carubbi2 and
  3. Javier Rodríguez-Carrio3
  1. 1Department of Medicine, Rheumatology Unit, University of Perugia, Perugia, Italy
  2. 2Department of Biotechnological and Applied Clinical Sciences, Rheumatology Unit, University of L’Aquila, L’Aquila, Italy
  3. 3University of Oviedo, Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain
  1. Correspondence to Alessia Alunno; alessia.alunno82{at}


Some of the articles being published during the severe acute respiratory syndrome–coronavirus (SARS-CoV)-2 pandemic highlight a link between severe forms of coronavirus disease 2019 (COVID-19) and the so-called cytokine storm, also with increased ferritin levels. However, this scenario is more complex than initially thought due to the heterogeneity of hyperinflammation. Some patients with coronavirus 2019 disease (COVID-19) develop a fully blown secondary haemophagocytic lymphohistiocytosis (sHLH), whereas others, despite a consistent release of pro-inflammatory cytokines, do not fulfil sHLH criteria but still show some features resembling the phenotype of the hyperferritinemic syndrome. Despite the final event (the cytokine storm) is shared by various conditions leading to sHLH, the aetiology, either infectious, autoimmune or neoplastic, accounts for the differences in the various phases of this process. Moreover, the evidence of a hyperinflammatory microenvironment provided the rationale to employ immunomodulating agents for therapeutic purposes in severe COVID-19. This viewpoint aims at discussing the pitfalls and issues to be considered with regard to the use of immunomodulating agents in COVID-19, such as timing of treatment based on the viral load and the extent of cytokine/ferritin overexpression. Furthermore, it encompasses recent findings in the paediatric field about a novel multisystem inflammatory disease resembling toxic shock syndrome and atypical Kawasaki disease observed in children with proven SARS-CoV2 infection. Finally, it includes arguments in favour of adding COVID-19 to the spectrum of the recently defined ‘hyperferritinemic syndrome’, which already includes adult-onset Still’s disease, macrophage activation syndrome, septic shock and catastrophic anti-phospholipid syndrome.

  • Sjøgren’s syndrome
  • Rheumatoid arthritis
  • T cells
  • Atherosclerosis
  • Autoantibodies
  • Inflammation
  • Cytokines
  • Early rheumatoid arthritis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

View Full Text

Statistics from


  • Contributors AA, FC and JRC drafted, read and approved the final manuscript.

  • Funding This article did not receive any specific funding. JRC was supported by Sara Borrell (CD19/00120) and PI (PI16/00113) programmes from Instituto de Salud Carlos III (Ministry of Science and Innovation, Spain).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.