Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a global public health emergency. Periodontitis, the most prevalent disease that leads to tooth loss, is caused by infection by periodontopathic bacteria. Periodontitis is also a risk factor for pneumonia and the exacerbation of chronic obstructive pulmonary disease, presumably because of the aspiration of saliva contaminated with periodontopathic bacteria into the lower respiratory tract. Patients with these diseases have increased rates of COVID-19 aggravation and mortality. Because periodontopathic bacteria have been isolated from the bronchoalveolar lavage fluid of patients with COVID-19, periodontitis may be a risk factor for COVID-19 aggravation. However, the molecular links between periodontitis and COVID-19 have not been clarified. In this study, we found that the culture supernatant of the periodontopathic bacterium Fusobacterium nucleatum (CSF) upregulated the SARS-CoV-2 receptor angiotensin-converting enzyme 2 in A549 alveolar epithelial cells. In addition, CSF induced interleukin (IL)-6 and IL-8 production by both A549 and primary alveolar epithelial cells. CSF also strongly induced IL-6 and IL-8 expression by BEAS-2B bronchial epithelial cells and Detroit 562 pharyngeal epithelial cells. These results suggest that when patients with mild COVID-19 frequently aspirate periodontopathic bacteria, SARS-CoV-2 infection is promoted, and inflammation in the lower respiratory tract may become severe in the presence of viral pneumonia.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) and is responsible for an ongoing pandemic
angiotensinconverting enzyme 2 (ACE2) protein expression was confirmed by Western blotting (Figure 1C) and immunofluorescence staining (Figure 1D) of A549 cells treated with culture supernatant of F. nucleatum (CSF)
We confirmed that brain heart infusion (BHI) broth does not affect the expression of ACE2 (Figure S1)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) and is responsible for an ongoing pandemic. Recent studies suggested that in addition to direct lung injury by SARS-CoV-2, a hyper-inflammatory response, referred to as the cytokine storm, contributes to disease severity in patients with. Periodontopathic bacteria were revealed to be involved in the pathogenesis of respiratory diseases, such as aspiration pneumonia and chronic obstructive pulmonary disease (COPD), and other systemic diseases, including diabetes and cardiovascular disease [6,7]. Such patients have increased rates of COVID-19 aggravation and mortality [8,9]. On the basis of the aforementioned observations, we hypothesized that increased counts of periodontopathic bacteria in the aspiration possibly induces ACE2 expression and proinflammatory cytokine production in the human respiratory epithelia
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