Why do children develop fewer severe forms of COVID-19 than adults?

Why do children develop fewer severe forms of COVID-19 than adults?

The bronchial epithelium is a tissue composed of several oriented cell layers of the

up (apical) down (basal). It is mainly composed of hair cells, mucus cells, club cells and basal cells which are installed on a basement membrane. The apical side is in contact with the air, while the basal side is in contact with the inside of the body. On the apical side, the ciliated cells bear cilia whose synchronized beats help to evacuate dust or pathogens, including viruses, from the surface of the epithelium. Mucus cells, present on the apical side, make mucus which serves to trap pathogens and contaminants from the air. The beating of the eyelashes of the hair cells will evacuate the mucus towards the throat where it will be swallowed and the pathogens inactivated.

The scientists used reconstructed bronchial epithelia in vitro. Using samples from different donors, the basal cells were cultured in wells, the lower part of which is porous and in contact with culture medium, while the apical part is in contact with the air, which mimics physiological conditions (air-liquid interface) and induces the differentiation of these cells into mucus cells and functional hair cells. Scientists reconstituted epithelia from adult and child donors, and infected them with SARS-CoV-2. The infection was followed over time by imaging and quantification of the virus by RT-qPCR. Using this “physiological” model, they showed that the bronchial epithelia were rapidly infected and released within a few days (3 to 4 days) large quantities of infected giant cells originating from the fusion of several cells, called syncytia. Such release of the virus could contribute to the severity of COVID-19 by allowing the virus to spread to the lower respiratory tract, or participate in dissemination in the environment.

By comparing infections from different donors, scientists found that some epithelia were partially resistant to infection. These epithelia rapidly secreted type III interferon, a soluble factor that can alert and protect epithelial cells against SARS-CoV-2 infection. When the gene responsible for interferon is deleted in these epithelia, viral infection is reestablished. Conversely, when the bronchial epithelia are treated with type III interferon, the spread of the virus is controlled and the bronchial epithelia are partially protected from infection. These “non-permissive” epithelia were more frequently observed from child donors, which could be related to the fact that children are less affected by severe forms of COVID-19 than adults.

© Harald Wodrich

Figure : 3D reconstruction of a reconstructed bronchial epithelium infected with SARS-CoV-2. Blue, nuclei; Red, actin labeling with phalloidin; Green, labeling of viral protein N; Magenta, cytokeratin 5, basal cell marker. One observes on the apical side of the epithelium, a syncitium doubly marked in pink and green.

To know more :
Bronchial epithelium of adults and children: spread of SARS-CoV-2 via syncytia formation and restriction of type III interferon infectivity.
Beucher G.Blondot ML, Celle A, Pied N, Recordon-Pinson P, Esteves P, Faure M, Métifiot M, Lacomme S, Dacheux D, Robinson DR, Längst G, Beaufils F, Lafon ME, Berger P, Landry M, Malvy D, Trian T, Andreola ML, Wodrich H.
Proc Natl Acad Sci US A. July 12, 2022. doi: 10.1073/pnas.2202370119.

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