COVID-19 - Prime Time for Microphysiological Systems, as Illustrated for the Brain

Ian Kang, Lena Smirnova, Jens H. Kuhn, Helena T. Hogberg, Nicole C. Kleinstreuer, Thomas Hartung

Research output: Contribution to journalArticlepeer-review


The development of therapies for and preventions against infectious diseases depends on the availability of disease models. Bioengineering of human organoids and organs-on-chips is one extremely promising avenue of research. These miniature, laboratory-grown organ systems have been broadly used during the ongoing, unprecedented coronavirus 2019 (COVID-19) pandemic to show the many effects of the etiologic agent, severe acute respiratory coronavirus 2 (SARS-CoV-2) on human organs. In contrast, exposure of most animals either did not result in infection or caused mild clinical signs - not the severe course of the infection suffered by many humans. This article illuminates the opportunities of microphysiological systems (MPS) to study COVID-19 in vitro, with a focus on brain cell infection and its translational relevance to COVID-19 effects on the human brain. Neurovirulence of SARS-CoV-2 has been reproduced in different types of human brain organoids by 10 groups, consistently showing infection of a small portion of brain cells accompanied by limited viral replication. This mirrors increasingly recognized neurological manifestations in COVID-19 patients (evidence of virus infection and brain-specific antibody formation in brain tissue and cerebrospinal fluid). The pathogenesis of neurological signs, their long-term consequences, and possible interventions remain unclear, but future MPS technologies offer prospects to address these open questions.

Original languageEnglish (US)
Pages (from-to)535-549
Number of pages15
Issue number4
StatePublished - 2021

ASJC Scopus subject areas

  • Pharmacology
  • Medical Laboratory Technology


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