Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2

Signal Transduct Target Ther. 2020 May 29;5(1):84. doi: 10.1038/s41392-020-0191-1.


To date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called "cytokine storm", clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Angiotensin-Converting Enzyme 2
  • Antiviral Agents / therapeutic use*
  • Betacoronavirus / drug effects*
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Cytokines / antagonists & inhibitors
  • Cytokines / genetics
  • Cytokines / immunology
  • Disease Progression
  • Gastrointestinal Microbiome / immunology
  • Gene Expression Regulation
  • Host-Pathogen Interactions / drug effects*
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunity, Innate / drug effects
  • Molecular Targeted Therapy
  • Pandemics*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / immunology
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology


  • Antiviral Agents
  • Cytokines
  • Spike Glycoprotein, Coronavirus
  • Toll-Like Receptors
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2