Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs

Stefania Scala, Roberto Pacelli

Research output: Contribution to journalReview articlepeer-review

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15-20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the "pattern recognition receptors" (PRR) of the immune cells that release cytokines activating more immune cells that produce a large number of pro-inflammatory cytokines, tissue factors and vasoactive peptides. Affected patients might develop the "cytokine storm syndrome," a fulminant and fatal hypercytokinaemia with multiorgan failure. In patients infected by SARS-COv-2 increase in T-helper 2 (TH2) cytokines (IL-4 and IL10) are reported in addition to the T-helper 1 (TH1) cytokines (IL1B, IFNγ, IP10, and MCP1) previously detected in other coronavirus infections. Cytokines and other molecules involved in immune response and inflammation are conceivable therapeutic targets for IP and ARDS, improving symptoms and decreasing intensive care unit admissions. To this aim off label drugs may be used taking into consideration the window timing for immunosuppressive drugs in virus infected patients. Some off label therapeutic options and preclinical evidence drugs are herein considered.

Original languageEnglish
Pages (from-to)1201
JournalFront. Immunol.
Volume11
DOIs
Publication statusPublished - Jun 24 2020

Keywords

  • Antiviral Agents/therapeutic use
  • Betacoronavirus/immunology
  • COVID-19
  • Coronavirus Infections/drug therapy
  • Critical Illness
  • Cytokines/blood
  • Humans
  • Off-Label Use
  • Pandemics
  • Pneumonia, Viral/drug therapy
  • SARS-CoV-2

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