Weathering the Cytokine Storm in COVID-19: Therapeutic Implications

Cardiorenal Med. 2020;10(5):277-287. doi: 10.1159/000509483. Epub 2020 Jun 29.


Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis.

Summary: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.

Keywords: COVID-19; Cytokine storm; Therapy.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Betacoronavirus
  • CCR5 Receptor Antagonists / therapeutic use
  • COVID-19
  • COVID-19 Drug Treatment
  • COVID-19 Serotherapy
  • Chloroquine / therapeutic use
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / immunology
  • Coronavirus Infections / therapy*
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / therapy*
  • Enzyme Inhibitors / therapeutic use
  • Extracorporeal Membrane Oxygenation
  • HIV Antibodies / therapeutic use
  • Hemoperfusion
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Immunization, Passive
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Factors / therapeutic use
  • Immunomodulation
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Janus Kinase Inhibitors / therapeutic use
  • Lung Injury / immunology
  • Lung Injury / therapy
  • Mesenchymal Stem Cell Transplantation
  • Multiple Organ Failure
  • Pandemics
  • Plasma Exchange
  • Plasmapheresis
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / therapy*
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Respiratory Distress Syndrome / immunology
  • Respiratory Distress Syndrome / therapy*
  • SARS-CoV-2
  • Tumor Necrosis Factor Inhibitors / therapeutic use


  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • CCR5 Receptor Antagonists
  • Enzyme Inhibitors
  • HIV Antibodies
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Interleukin 1 Receptor Antagonist Protein
  • Janus Kinase Inhibitors
  • Receptors, Interleukin-6
  • Tumor Necrosis Factor Inhibitors
  • Hydroxychloroquine
  • Chloroquine
  • tocilizumab
  • leronlimab