The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease

Autoimmun Rev. 2020 Jun;19(6):102537. doi: 10.1016/j.autrev.2020.102537. Epub 2020 Apr 3.

Abstract

Severe COVID-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). This is distinct from HLH associated with immunodeficiency states termed primary HLH -with radically different therapy strategies in both situations. COVID-19 infection with MAS typically occurs in subjects with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. We provide a model for the classification of MAS to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning ARDS from MAS. We discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.

Publication types

  • Review

MeSH terms

  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity
  • Coronavirus Infections / complications*
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / pathology
  • Humans
  • Interleukin-1 / immunology
  • Interleukin-6 / immunology*
  • Lymphohistiocytosis, Hemophagocytic / complications
  • Lymphohistiocytosis, Hemophagocytic / immunology
  • Macrophage Activation Syndrome / complications
  • Macrophage Activation Syndrome / immunology*
  • Macrophage Activation Syndrome / pathology
  • Pandemics
  • Pneumonia, Viral / complications*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / pathology
  • Respiratory Distress Syndrome, Adult / complications
  • Respiratory Distress Syndrome, Adult / immunology*
  • Respiratory Distress Syndrome, Adult / pathology

Substances

  • Interleukin-1
  • Interleukin-6

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2