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Stem Cell Rev Rep ; 17(6): 2107-2119, 2021 12.
Article in English | MEDLINE | ID: covidwho-1345193


The virus responsible for coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over 190 million people to date, causing a global pandemic. SARS-CoV-2 relies on binding of its spike glycoprotein to angiotensin-converting enzyme 2 (ACE2) for infection. In addition to fever, cough, and shortness of breath, severe cases of SARS-CoV-2 infection may result in the rapid overproduction of pro-inflammatory cytokines. This overactive immune response is known as a cytokine storm, which leads to several serious clinical manifestations such as acute respiratory distress syndrome and myocardial injury. Cardiovascular disorders such as acute coronary syndrome (ACS) and heart failure not only enhance disease progression at the onset of infection, but also arise in hospitalized patients with COVID-19. Tissue-specific differentiated cells and organoids derived from human pluripotent stem cells (hPSCs) serve as an excellent model to address how SARS-CoV-2 damages the lungs and the heart. In this review, we summarize the molecular basis of SARS-CoV-2 infection and the current clinical perspectives of the bidirectional relationship between the cardiovascular system and viral progression. Furthermore, we also address the utility of hPSCs as a dynamic model for SARS-CoV-2 research and clinical translation.

COVID-19/virology , Cardiovascular System/virology , Pluripotent Stem Cells/virology , COVID-19/immunology , Cardiovascular Diseases/immunology , Cardiovascular Diseases/virology , Cardiovascular System/immunology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Humans , Lung/immunology , Lung/virology , Pandemics/prevention & control , Pluripotent Stem Cells/immunology , SARS-CoV-2/pathogenicity
Nat Rev Immunol ; 21(7): 441-453, 2021 07.
Article in English | MEDLINE | ID: covidwho-1007586


Advancements in human pluripotent stem cell technology offer a unique opportunity for the neuroimmunology field to study host-virus interactions directly in disease-relevant cells of the human central nervous system (CNS). Viral encephalitis is most commonly caused by herpesviruses, arboviruses and enteroviruses targeting distinct CNS cell types and often leading to severe neurological damage with poor clinical outcomes. Furthermore, different neurotropic viruses will affect the CNS at distinct developmental stages, from early prenatal brain development to the aged brain. With the unique flexibility and scalability of human pluripotent stem cell technology, it is now possible to examine the molecular mechanisms underlying acute infection and latency, determine which CNS subpopulations are specifically infected, study temporal aspects of viral susceptibility, perform high-throughput chemical or genetic screens for viral restriction factors and explore complex cell-non-autonomous disease mechanisms. Therefore, human pluripotent stem cell technology has the potential to address key unanswered questions about antiviral immunity in the CNS, including emerging questions on the potential CNS tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Central Nervous System/immunology , Host Microbial Interactions/immunology , Pluripotent Stem Cells/immunology , Viral Tropism , COVID-19 , Humans , Microglia , Neuroglia , Neurons , SARS-CoV-2