Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19

Zhang, Zhao; Guo, Liyan; Lu, Xin-Jiang; Che, Zhang; Huang, Li; Wang, Xianfeng; Duan, Fuyu; Liang, Huiying; Chen, Peikai; Zeng, Liang; Shao, Jianbo; Li, Hui; Li, Le; Liu, Li; Li, Cheng; Zhang, Jinqiu; Yan, Chui; Kwan, Ka Yi; Liu, Wei; Xu, Yi; Gu, Xiaoqiong; Jiang, Hua; Du, Hui; Zhang, Ting; Wu, Yanheng; Guo, Yu; Chen, Junhui; Luo, Ruibang; Liao, Can; Tse, Hung Fat; Chen, Zhiwei; Chen, Huanhuan Joyce; Xia, Huimin; Lian, Qizhou

doi:10.7150/thno.53136

Cited by 19 publications

(23 citation statements)

References 30 publications

(36 reference statements)

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“…The studies included for the qualitative analysis were as follows: Scagnolari et al [ 32 ], Sajuthi et al [ 33 ], Somekh et al [ 34 ], Bunyavanich et al [ 35 ], Swärd et al, [ 36 ], Taglauer et al [ 37 ], Vuille-Dit-Bille et al [ 38 ], Zhang et al [ 28 ], Galván-Peña et al [ 39 ], Koch et al [ 30 ], Ortiz Bezara et al [ 40 ], Sharif-Askari et al [ 41 ], Schweitzer et al [ 42 ], Pavel et al [ 43 ], Yonker et al [ 29 ], Inde et al [ 44 ], Zhang et al [ 45 ], and Heinonen et al [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…Children have the same risk of infection with SARS-CoV-2 as the general population, with the most severe cases found in newborns [ 45 , 47 ]. However, disease severity is frequently lower in children than in adults, with a benign or moderate course, in the absence of risk factors or concomitant diseases [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…ACE2 appears to be expressed mostly on the apical surface of the well-differentiated cells lining lung alveoli, where it causes the greatest damage [ 59 ]. In particular, according to a recent study conducted by Ortiz Bezara et al, the apical cell surfaces of a small subgroup of alveolar type II cells [ 40 ], are mainly involved with SOX9 positive lung progenitor cells (pluripotent stem cells also present in the lungs of children) [ 45 ]. In addition, strong expression was also demonstrated in the mouth and tongue, implicating the oral cavity as a route of infection [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

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Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection

et al. 2021

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COVID-19 (Coronavirus Disease 2019) is an emerging viral disease caused by the coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which leads to severe respiratory infections in humans. The first reports came in December 2019 from the city of Wuhan in the province of Hubei in China. It was immediately clear that children developed a milder disease than adults. The reasons for the milder course of the disease were attributed to several factors: innate immunity, difference in ACE2 (angiotensin-converting enzyme II) receptor expression, and previous infections with other common coronaviruses (CovH). This literature review aims to summarize aspects of innate immunity by focusing on the role of ACE2 expression and viral infections in children in modulating the antibody response to SARS-CoV-2 infection. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles deemed potentially eligible were considered, including those dealing with COVID-19 in children and providing more up-to-date and significant data in terms of epidemiology, prognosis, course, and symptoms, focusing on the etiopathogenesis of SARS-CoV-2 disease in children. The bibliographic search was conducted using the search engines PubMed and Scopus. The following search terms were entered in PubMed and Scopus: COVID-19 AND ACE2 AND Children; COVID-19 AND Immunity innate AND children. The search identified 857 records, and 18 studies were applicable based on inclusion and exclusion criteria that addressed the issues of COVID-19 concerning the role of ACE2 expression in children. The scientific literature agrees that children develop milder COVID-19 disease than adults. Milder symptomatology could be attributed to innate immunity or previous CovH virus infections, while it is not yet fully understood how the differential expression of ACE2 in children could contribute to milder disease.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection

et al. 2021

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“…Furthermore, it is noteworthy to include that neonates (<1 year of age) have increased vulnerability to COVID-19 infection than children. It has been shown that neonates have a higher number of ACE2-positive progenitor cells (resident in their lung) that make them susceptible to infection with SARS-CoV-2 [113]. By comparison, the number of progenitor cells in the lung is significantly decreased in older children.…”

Section: Ace/ace2 Ratiomentioning

confidence: 99%

A Review on the Role of Stem Cells against SARS-CoV-2 in Children and Pregnant Women

Sanie-Jahromi

NejatyJahromy

Jahromi

2021

IJMS

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Since the COVID-19 outbreak was acknowledged by the WHO on 30 January 2020, much research has been conducted to unveil various features of the responsible SARS-CoV-2 virus. Different rates of contagion in adults, children, and pregnant women may guide us to understand the underlying infection conditions of COVID-19. In this study, we first provide a review of recent reports of COVID-19 clinical outcomes in children and pregnant women. We then suggest a mechanism that explains the curious case of COVID-19 in children/pregnant women. The unique stem cell molecular signature, as well as the very low expression of angiotensin-converting enzyme 2 and the lower ACE/ACE2 ratio in stem cells of children/pregnant women compared to adults might be the cause of milder symptoms of COVID-19 in them. This study provides the main molecular keys on how stem cells can function properly and exert their immunomodulatory and regenerative effects in COVID-19-infected children/pregnant women, while failing to replicate their role in adults. This can lay the groundwork for both predicting the pattern of spread and severity of the symptoms in a population and designing novel stem cell-based treatment and prevention strategies for COVID-19.

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“…Involving regulation of virus infection, e.g., SARS-CoV-2, IAV [145][146][147][148][149][150][151][152][153] Jak-STAT signaling pathway…”

Section: Kegg Pathway Potential Role During Sars-cov-2 Infection Induced By Reported Evidence Nf-kappa B Signaling Pathwaymentioning

confidence: 99%

Integrated Analysis of microRNAs and Metabolomics in Rat’s Serum Reveals Multi-action Modes of Qingfei Paidu Decoction for COVID-19 Treatment

Li¹,

Liu²,

Liao³

et al. 2021

Preprint

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Background During the fight against coronavirus disease 2019 (COVID-19) in China, Qingfei Paidu decoction (QFPDD) has been widely applied to treat COVID-19 patients. Retrospective studies showed that QFPDD could improve clinical outcomes of COVID-19. Thus, it is necessary and interesting to explore the action mode of QFPDD for further application and development.MethodsSprague-Dawley (SD) rats were randomly divided into two groups, QFPDD (n=9) and control (n=10) groups. They were parallelly treated for 12 days with QFPDD and warm distilled water, respectively. At the endpoint, the microRNA (miRNA or miR) profiles in serum were detected to identify differently expressed miRNAs (DEMs). Then, the action mode of QFPDD were explored via review of potential roles of DEMs and functional enrichment analysis of their targets (e.g., GO enrichment and KEGG pathway analysis), especially focusing on the aspects of immunity, inflammation, virus infection and pulmonary fibrosis. Core genes were identified based on KEGG pathway analysis. Metabolomics were detected in serum and significantly changed metabolites (SCMs), especially the metabolic substrates and products of enzyme of core gene were identified as biomarkers to validate the regulation of DEMs to enzyme activity of core gene through metabolomic analysis and linear correlation analysis between SCMs and DEMs. Results23 DEMs were identified in the serum between QFPDD and control groups, with 1636 predicted genes. Reported evidence has showed that both the DEMs and their target genes involve regulation of immunity, inflammation, virus infection and pulmonary fibrosis. Phospholipase C, gamma 1 (Plcg1) was identified as a core gene and predicted to be upregulated attributed to downregulation of novel-89-mature. The levels of three SCMs, PC(P-18:1(11Z)/22:5(4Z,7Z,10Z,13Z,16Z)), PC(22:5(4Z,7Z,10Z,13Z,16Z)/P-18:0) and PC(16:1(9Z)/16:1(9Z)), which were the metabolic substrates of phospholipase C, were significantly reduced in QFPDD group, in addition, PC(P-18:1(11Z)/22:5(4Z,7Z,10Z,13Z,16Z)) and PC(22:5(4Z,7Z,10Z,13Z,16Z)/P-18:0) presented positively linear correlation with the expression level of novel-89-mature. The level of phosphorylcholine, a product of PCs metabolized by phospholipase C, was significantly elevated in QFPDD group. Conclusion QFPDD can induce modification of miRNAs profile, and subsequently multi-regulate the immunity, inflammation, virus infection and pulmonary fibrosis in vivo, playing an important role for the positive outcomes of COVID-19 patients treated by QFPDD in China.

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Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19

Cited by 19 publications

References 30 publications

Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection

Innate Immunity in Children and the Role of ACE2 Expression in SARS-CoV-2 Infection

A Review on the Role of Stem Cells against SARS-CoV-2 in Children and Pregnant Women

Integrated Analysis of microRNAs and Metabolomics in Rat’s Serum Reveals Multi-action Modes of Qingfei Paidu Decoction for COVID-19 Treatment

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