RHEUMATOLOGICAL ASPECTS AND TREATMENTS OF COVID-19: Edited by Rebecca H. HabermanIs severe COVID-19 a cytokine storm syndrome: a hyperinflammatory debateMehta, Pujaa,b; Fajgenbaum, David C.c Author Information aCentre for Inflammation and Tissue Repair, UCL Respiratory, Division of Medicine, University College London bDepartment of Rheumatology, University College London Hospital (UCLH), London, UK cDepartment of Medicine, Division of Translational Medicine and Human Genetics, Center for Cytokine Storm Treatment and Laboratory, Philadelphia, Pennsylvania, USA Correspondence to Puja Mehta, MD, Centre for Inflammation and Tissue Repair, UCL Respiratory, Division of Medicine, University College London, London, UK. E-mail: [email protected]. Current Opinion in Rheumatology: September 2021 - Volume 33 - Issue 5 - p 419-430 doi: 10.1097/BOR.0000000000000822 Buy Metrics Abstract Purpose of review The COVID-19 pandemic is a global public health crisis with considerable mortality and morbidity. A role for cytokine storm and therapeutic immunomodulation in a subgroup of patients with severe COVID-19 was proposed early in the pandemic. The concept of cytokine storm in COVID-19 has been criticised, given the lack of clear definition and relatively modest cytokinaemia (which may be necessary for viral clearance) compared with acute respiratory distress syndrome and bacterial sepsis. Here we consider the arguments for and against the concept of cytokine storm in COVID-19. Recent findings Several criteria have been proposed to identify the subgroup of COVID-19 patients exhibiting a cytokine storm. The beneficial effects of corticosteroids and interleukin-6 inhibition suggest that inflammation is a modifiable pathogenic component of severe COVID-19. The presence of genetic polymorphisms and pathogenic auto-autoantibodies in severe COVID-19 also suggests a significant contribution of immune dysregulation to poor outcomes. Summary Hyperinflammation is a key component of severe COVID-19, residing underneath the cytokine storm umbrella term, associated with poor outcomes. Better understanding of the aetiopathogenesis, with identification of biomarkers to predict treatment responses and prognosis, will hopefully enable a stratified and ultimately precision medicine approach. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.