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

Chiu, Man Chun; Li, Cun; Liu, Xiaojuan; Song, Wenjun; Wan, Zhixin; Yu, Yifei; Huang, Jingjing; Xiao, Ding; Chu, Hin; Cai, Jian‐Piao; To, Kelvin Kai-Wang; Yuen, Kwok Yung; Zhou, Jie

doi:10.1128/mbio.01944-22

Cited by 38 publications

(54 citation statements)

References 50 publications

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“…In experimentally infected human bronchial epithelial cells, MAP3K19 expression was acutely up-regulated after SARS-CoV-2 infection but then progressively down-regulated compared to controls (Figure S9). Furthermore, the percentage of one of the cilium cell types (Figure 3A-B), ciliated cells (Ciliated), is signi cantly lower in critical COVID-19 patients than healthy controls (Figure 3A-D), in consistent with previous report that SARS-CoV-2 is able to deplete ciliated cells [27]. No difference in the distribution of other cell types was observed across patient groups.…”

Section: Resultssupporting

confidence: 90%

MAP3K19 regulatory variation in populations with African ancestry is associated with severe COVID-19

Cheng

Cai

Zhang

et al. 2022

Preprint

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Ancestry impacts the likelihood of hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). To identify ancestry-linked genetic risk variants associated with COVID-19 hospitalization, we performed an integrative analysis of two genome-wide association studies (GWASs) evaluating genetic variation among ancestrally diverse cohorts. We resolved four single nucleotide polymorphisms (SNPs) that are more frequent in COVID-19 hospitalized patients with non-European ancestry than the general population. Among them, the COVID-19 risk SNP rs16831827 shows the largest difference in allele frequency between African and European populations. The minor allele frequency of rs16831827*T was significantly higher in hospitalized COVID-19 patients with African ancestry. SNP rs16831827 also associates with COVID-19 hospitalization in an independent GWAS from the UK Biobank wherein both the hospitalized and control patients are entirely of African ancestry. rs16831827 is an expression quantitative trait locus (eQTL) of MAP3K19. Apart from rs16831827, two rare SNPs of MAP3K19, rs186150828 and rs192473276, were also significantly associated with COVID-19 hospitalization among African populations in the Regeneron COVID-19 hospitalization GWAS (p < 5x10-7). MAP3K19 expression is induced during ciliogenesis and most abundant in ciliated tissues including the lung and testis. Multiple COVID-19 related single-cell RNA sequencing data revealed that MAP3K19 is highly expressed in nasal multiciliated epithelial cells, nasopharyngeal ciliated cells, and airway ciliated cells. The COVID-19 hospitalization risk allele rs16831827*T is associated with reduced MAP3K19 expression. Hence, rs16831827 may increase the risk of severe COVID-19 by reducing baseline MAP3K19 expression.

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Section: Resultssupporting

confidence: 90%

MAP3K19 regulatory variation in populations with African ancestry is associated with severe COVID-19

Cheng

Cai

Zhang

et al. 2022

Preprint

Self Cite

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“…Numerous studies showed the usefulness of organoid models in the evaluation of SARS-CoV-2 variants infectivity, such as using human airway, alveolar and intestinal organoid models to study the Alpha variant (B.1.1.7) [104] and nasal epithelium-derived organoid culture system to show high infectivity potential of the Omicron and Delta variants than in comparison with other VOC. [105]. Several mutations in SARS-CoV-2 variants target the S1 domain of the S protein, in addition to those already occurring in the RBD, which cause the affinity enhancement of the virus to the human ACE2 receptor and as a result, increase the transmissibility of the virus.…”

Section: Sars-cov-2 Variantsmentioning

confidence: 99%

Insights into organoid-based modeling of COVID-19 pathology

Boroojerdi

Jabry

Mirarefin

et al. 2023

Virol J

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Since December 2019, various types of strategies have been applied due to the emergent need to investigate the biology and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to discover a functional treatment. Different disease modeling systems, such as mini-organ technology, have been used to improve our understanding of SARS-CoV-2 physiology and pathology. During the past 2 years, regenerative medicine research has shown the supportive role of organoid modeling in controlling coronavirus disease 2019 (COVID-19) through optimal drug and therapeutic approach improvement. Here, we overview some efforts that have been made to study SARS-CoV-2 by mimicking COVID-19 using stem cells. In addition, we summarize a perspective of drug development in COVID-19 treatment via organoid-based studies.

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“…As the primary target and entry portal of respiratory pathogens, nasal epithelial cells also express high levels of SARS-CoV-2 entry factors that favor robust SARS-CoV-2 replication, which constitutes the biological basis underlying viral pathogenesis and viral shedding ( 14 ). Thus, the measurement of viral replicative fitness in this organ could be a surrogate test for potential human spread.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the measurement of viral replicative fitness in this organ could be a surrogate test for potential human spread. Human nasal organoids were prepared as previously reported ( 14 ). Next, we examined SARS-CoV-2, BtCoV-WIV1, and PCoV-GX replication kinetics in nasal organoids derived from healthy donors.…”

Section: Resultsmentioning

confidence: 99%

Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin

Yang

Shen

Zhang

et al. 2023

mBio

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

Abstract: An in vitro model of the nasal epithelium is imperative for understanding cell biology and virus-host interaction in the human upper respiratory tract. Here we report an organoid culture system of the nasal epithelium.

Cited by 38 publications

References 50 publications

MAP3K19 regulatory variation in populations with African ancestry is associated with severe COVID-19

MAP3K19 regulatory variation in populations with African ancestry is associated with severe COVID-19

Insights into organoid-based modeling of COVID-19 pathology

Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin

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