Interferons (IFNs) are secreted by a variety of cells (inflammatory, fibroblasts, endothelial cells, epithelial cells, etc.) and are responsible for activation of signal transduction cascade leading to expression of myriads of genes. All the IFN-stimulated genes play vital roles that include antimicrobial defense, antiproliferative activities and upregulation of adaptive immunity [1]. Intriguingly, IFN has been identified as an important driver molecule responsible for the expression of ACE2 in lungs and nasal mucosa [2].
Hypothesis: Patients with interferon expressing oral pathologies are susceptible to COVID-19 infection.
Like any other organ, the oral cavity can be affected by many pathological conditions, which are characterized by up-regulation of IFN. Oral epithelial cells are known to express a certain subset of type I IFN and IFN-stimulated genes when subject to different kind of stresses [3]. Oral conditions such as aphthous ulcerations, lichen planus, herpes viral infection, candidiasis are the most common pathologies expressing IFN. Hence, it is quite conceivable to anticipate the expression and stimulation of a myriad of interferon-stimulated genes in the oral cavity including ACE2. In other words, the expression of ACE2 in the oral cavity and salivary glands is very much dependent on the presence of IFN activity. Variation in the IFN activity could drive the inter-individual heterogeneity in ACE2 expression in the oral cavity and this can percolate further to cause heterogeneity in COVID-19 clinical manifestations. A recent study has identified variations in ACE2 expression in various regions of the oral cavity with the tongue being the most common site [4]. We believe that this differential expression could be a focal effect of IFN-mediated activation of ACE2 genes and studies are warranted in this direction.
If the above contention holds true, then patients with IFN-related oral disorders such as aphthous ulcerations, lichen planus, herpes viral infections, etc. would be more prone to COVID-19 infection. We also register the concern about the oral sites like gingival sulcus and tongue due to their constant association with pathogenic microorganisms and inflammation, which can manifest IFN up-regulation at these sites [5]. Thus, there is a dire need for in-depth investigation on ACE2 as well as TMPRSS2 distribution and quantification at various sites of the oral cavity with special emphasis on the oral pathologies that can heighten IFN expression.
Funding source
The authors received no specific funding for this work.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.mehy.2020.110179.
Appendix A. Supplementary data
The following are the Supplementary data to this article:
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