TY - JOUR
T1 - COVID-19 - Prime Time for Microphysiological Systems, as Illustrated for the Brain
AU - Kang, Ian
AU - Smirnova, Lena
AU - Kuhn, Jens H.
AU - Hogberg, Helena T.
AU - Kleinstreuer, Nicole C.
AU - Hartung, Thomas
N1 - Funding Information:
We thank Anya Crane (National Institutes of Health [NIH] National Institute of Allergy and Infectious Diseases [NIAID] Division of Clinical Research [DCR] Integrated Research Facility at Fort Detrick [IRF-Frederick]) for critically editing the manuscript. This work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C.
Publisher Copyright:
© The Authors, 2021.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
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U2 - 10.14573/altex.2110131
DO - 10.14573/altex.2110131
M3 - Article
C2 - 34698363
AN - SCOPUS:85120835400
SN - 1868-596X
VL - 38
SP - 535
EP - 549
JO - ALTEX
JF - ALTEX
IS - 4
ER -