Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Children typically experience more mild symptoms of COVID-19 when compared to adults. There is a strong body of evidence that children are also less susceptible to SARS-CoV-2 infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remains to be determined. Here, we use primary nasal epithelial cells from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the nasal epithelial cells of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the nasal epithelial cells of children. Importantly, the Delta variant also replicated to significantly lower titres in the nasal epithelial cells of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.
Article activity feed
-
-
-
SciScore for 10.1101/2021.03.08.434300: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was approved by the University of Queensland’s Human Research Ethics Committee (2020001742). Randomization not detected. Blinding Sections were assessed for cellular morphology by a veterinary pathologist (H.B.) blinded to the experimental design. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cell culture: African green monkey kidney epithelial Vero cells and Madin-Dkarby Canine Kidney (MDCK) cells were obtained from American Type Culture Collection (ATCC; Virginia, MDCKsuggested: CLS Cat# 602280/p823_MDCK_(NBL-2, RRID:CVCL_0422)SciScore for 10.1101/2021.03.08.434300: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was approved by the University of Queensland’s Human Research Ethics Committee (2020001742). Randomization not detected. Blinding Sections were assessed for cellular morphology by a veterinary pathologist (H.B.) blinded to the experimental design. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Cell culture: African green monkey kidney epithelial Vero cells and Madin-Dkarby Canine Kidney (MDCK) cells were obtained from American Type Culture Collection (ATCC; Virginia, MDCKsuggested: CLS Cat# 602280/p823_MDCK_(NBL-2, RRID:CVCL_0422)Quantification of infectious virus: SARS-CoV-2 titres in cell culture supernatants were determined by plaque assay on Vero cells, as described previously (28). Verosuggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)Software and Algorithms Sentences Resources RNA Sequencing analysis: Deferentially expressed genes (DEGs) were identified using DESeq2 (30) in R. DESeq2suggested: (DESeq, RRID:SCR_000154)Gene Ontology enrichment analysis was performed using the R package GOseq. GOseqsuggested: (Goseq, RRID:SCR_017052)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Finally, it is important to recognize the limitations of this study. Due to the difficulties associated with obtaining NECs from children only a limited number of donors could be used. However, as donors were not selected on susceptibility to respiratory viral infection their responses should be broadly representative of other healthy children. Furthermore, our data focused on the role of nasal epithelial cells in age-dependent differences in SARS-CoV-2 infection. However, there can be a number of other mechanisms to explain the reduced susceptibility of children to SARS-CoV-2 infection that were not measured in the present study. For example, children and adolescents have much higher titres of preexisting antibodies to SARS-CoV-2 compared to adults (14, 54). This study is unable to ascertain if this plays a more significant role than the nasal epithelium in protecting children from infection in vivo. Finally, it is important to recognize that these in vitro studies were performed with an early SARS-CoV-2 isolate and therefore did not represent the viral mutations that are currently circulating in the community. This remains an area of ongoing research in our laboratory. In sum, the data presented here suggest that the nasal epithelium of children is distinct and that it may afford children some level of protection from SARS-CoV-2 infection.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
-