The Dynamic Expression of Potential Mediators of Severe Acute Respiratory Syndrome Coronavirus 2 Cellular Entry in Fetal, Neonatal, and Adult Rhesus Monkeys.

Bangrong Cao,Liping Zhang,Kun Mi,Shiqi Ma,Huifen Liu

doi:10.3389/fgene.2020.607479

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, induced by the pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly all over the world. There is considerable variability among neonates, children, and adults in the incidence of infection and severe disease following exposure to SARS-CoV-2. In our study, we analyzed the transcriptome data of primate animal model of Rhesus monkeys to evaluate the expression levels of possible SARS-CoV-2 receptors and proteases and immunologic features in the lungs, colons, livers, and brains at different developmental stages. Our results revealed that ACE2 and TMPRSS2 were highly expressed in neonates compared with other populations, which imply the high incidence of infection. Other potential receptors and Type II transmembrane serine proteases (TTSPs) and cathepsin of endosomal proteases also exhibited dynamic and differential expression patterns. The expression of receptors (ACE2, BSG, and DPP4) and proteases (TMPRSS2, TMPRSS9, CTSL, and CTSB) were highly correlated during lung development, suggesting the high susceptibility of the lungs. TMPRSS9 was specifically highly expressed in the lungs and reached the highest level in neonates, similar to TMPRSS2. Moreover, the immune cell infiltration analysis revealed immunity immaturity in neonates, implying the association with the mild or moderate type of COVID-19. The results might help researchers design protective and therapeutic strategies for COVID-19 in populations at different ages.

Highlights

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly all over the world with significant public health concerns
We explored the expression levels of SARS-CoV-2 cellular entry-related receptors and protease genes in the lungs, colons, livers, and brains of Rhesus monkey in different developmental stages of F45d–F70d, F100d, and F157d of fetuses, neonates, and adults
The roles of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) have been confirmed in SARS-CoV-2 cellular entry activities (Hoffmann et al, 2020; Ziegler et al, 2020)

Summary

Introduction

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly all over the world with significant public health concerns. By September 14, 2020, the COVID-19 pandemic has resulted in approximately 29 million cases and over 9,22,000 deaths worldwide. Dynamic Expression of SARS-CoV-2 Mediators over 90,000 confirmed cases and 4,700 deaths. The epidemiological and clinical patterns of the COVID-19 remain largely unclear among neonates and children. The epidemiological characteristics of pediatric patients with COVID-19 in China have indicated that young children, infants, were vulnerable to SARS-CoV-2 infection (Dong et al, 2020). Neonatal cases showed that similar to older children, most neonates with COVID-19 were asymptomatic (20%) or had mild (48%) and moderate (20%) signs of clinical infection (Liguoro et al, 2020). A higher proportion of asymptomatic carriers in neonates and children could make them effective carriers to spread the viruses (Gandhi et al, 2020). There is an urgent need to identify the molecular mechanisms that mediate viral entry, propagation, and viral susceptibility in this population

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Results

Conclusion