Coronavirus disease 2019: investigational therapies in the prevention and treatment of hyperinflammation

on behalf of the COVID-19 Global Rheumatology Alliance

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations


Introduction: The mortality of coronavirus disease 2019 (COVID-19) is frequently driven by an injurious immune response characterized by the development of acute respiratory distress syndrome (ARDS), endotheliitis, coagulopathy, and multi-organ failure. This spectrum of hyperinflammation in COVID-19 is commonly referred to as cytokine storm syndrome (CSS). Areas covered: Medline and Google Scholar were searched up until 15th of August 2020 for relevant literature. Evidence supports a role of dysregulated immune responses in the immunopathogenesis of severe COVID-19. CSS associated with SARS-CoV-2 shows similarities to the exuberant cytokine production in some patients with viral infection (e.g.SARS-CoV-1) and may be confused with other syndromes of hyperinflammation like the cytokine release syndrome (CRS) in CAR-T cell therapy. Interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha have emerged as predictors of COVID-19 severity and in-hospital mortality. Expert opinion: Despite similarities, COVID-19-CSS appears to be distinct from HLH, MAS, and CRS, and the application of HLH diagnostic scores and criteria to COVID-19 is not supported by emerging data. While immunosuppressive therapy with glucocorticoids has shown a mortality benefit, cytokine inhibitors may hold promise as ‘rescue therapies’ in severe COVID-19. Given the arguably limited benefit in advanced disease, strategies to prevent the development of COVID-19-CSS are needed.

Original languageEnglish
Pages (from-to)1185-1204
Number of pages20
JournalExpert Review of Clinical Immunology
Issue number12
StatePublished - 2020


  • Coronavirus disease 2019 (COVID-19)
  • cytokine release syndrome
  • cytokine storm syndrome
  • hemophagocytic lymphohistiocytosis
  • hyperinflammation


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