Review of studies of severe acute respiratory syndrome related coronavirus-2 pathogenesis in human organoid models

Rev Med Virol. 2021 Nov;31(6):e2227. doi: 10.1002/rmv.2227. Epub 2021 Mar 25.

Abstract

Severe acute respiratory syndrome related coronavirus-2 (SARS-CoV-2) is the cause of Covid-19 which was classified as a global pandemic in March 2020. The increasing global health and economic burden of SARS-CoV-2 has necessitated urgent investigations into the pathogenesis of disease and development of therapeutic and vaccination regimens. Human trials of vaccine and antiviral candidates have been undertaken, but basic pathogenetic studies are still required to inform these trials. Gaps in understanding of cellular infection by, and immunity to, SARS-CoV-2 mean additional models are required to assist in improved design of these therapeutics. Human organoids are three-dimensional models that contain multiple cell types and mimic human organs in ex vivo culture conditions. The SARS-CoV-2 virus has been implicated in causing not only respiratory injury but also injury to other organs such as the brain, liver and kidneys. Consequently, a variety of different organoid models have been employed to investigate the pathogenic mechanisms of disease due to SARS-CoV-2. Data on these models have not been systematically assembled. In this review, we highlight key findings from studies that have utilised different human organoid types to investigate the expression of SARS-CoV-2 receptors, permissiveness, immune response, dysregulation of cellular functions, and potential antiviral therapeutics.

Keywords: Covid-19; SARS-CoV-2; antivirals; immune response; organoids; pathogenesis.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / antagonists & inhibitors
  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / immunology
  • Antiviral Agents / pharmacology
  • Brain / drug effects
  • Brain / immunology
  • Brain / virology
  • COVID-19 / immunology
  • COVID-19 / pathology
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Cell Culture Techniques
  • Colon / drug effects
  • Colon / immunology
  • Colon / virology
  • Cytokines / genetics
  • Cytokines / immunology
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Liver / drug effects
  • Liver / immunology
  • Liver / virology
  • Lung / drug effects
  • Lung / immunology
  • Lung / virology
  • Models, Biological*
  • Organoids / drug effects
  • Organoids / immunology*
  • Organoids / virology
  • Receptors, Virus / antagonists & inhibitors*
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / immunology
  • Spike Glycoprotein, Coronavirus / antagonists & inhibitors*
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antiviral Agents
  • Cytokines
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human