The Human Nose Organoid Respiratory Virus Model: an Ex Vivo Human Challenge Model To Study Respiratory Syncytial Virus (RSV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pathogenesis and Evaluate Therapeutics

Abstract

Preclinical models that recapitulate aspects of human airway disease are essential for the advancement of novel therapeutics and vaccines. Here, we report a versatile airway organoid model, the human nose organoid (HNO), that recapitulates the complex interactions between the host and virus.

Human Nasal Organoids Model SARS-CoV-2 Upper Respiratory Infection and Recapitulate the Differential Infectivity of Emerging Variants

“…When the study was approaching the end, Rajan et al recently reported a human “nose organoid” model ( 44 ). Interestingly, the authors also established nose organoids based on our reported protocol of generating human airway organoids ( 18 , 19 ).…”

COVID-19 Causes Ciliary Dysfunction as Demonstrated by Human Intranasal Micro-Optical Coherence Tomography Imaging

“…These characteristics have included prominent infection of the ciliated cells, in addition to disruption of cilia synchronicity and cilium shrinkage with decreased ciliary beating demonstrated in differentiated human tracheobronchial epithelial (HTBE) cells (7, 10, 29), nasal ciliated cells from human and non-human primates (5), Syrian hamsters (11, 30, 31), and SARS-CoV-2 infected human nasal organoids. (32) In addition, diminished mucociliary clearance by SARS-CoV-2 has been demonstrated in HTBE cells by tracking polystyrene beads (10) and in Syrian hamsters by µOCT imaging. (11)…”

“…These characteristics have included prominent infection of the ciliated cells, in addition to disruption of cilia synchronicity and cilium shrinkage with decreased ciliary beating demonstrated in differentiated human 10 tracheobronchial epithelial (HTBE) cells (7,10,29), nasal ciliated cells from human and non-human primates (5), Syrian hamsters (11,30,31), and SARS-CoV-2 infected human nasal organoids. (32) In addition, diminished mucociliary clearance by SARS-CoV-2 has been demonstrated in HTBE cells by tracking polystyrene beads (10) and in Syrian hamsters by µOCT imaging. (11) By intention, due to requirements for conducting safe and effective nasal imaging under isolation conditions, our disease cohort had mild COVID-19 illness.…”

In vitro high-content tissue models to address precision medicine challenges

“…Rajan et al engineered human nose organoids and further infected them with SARS-CoV-2 as a model to study respiratory viruses and test therapeutics that could function as an alternative model to lung organoids ( Rajan et al, 2022 ). To study potential audiovestibular dysfunction as a result from SARS-CoV-2 infection, Jeong et al prepared human air organoids that successfully expressed the important components of ACE2, TMPRSS2, and FURIN cofactors for SARS-CoV-2 entry ( Jeong et al, 2021 ).…”