key: cord-0942061-v4zhz80s
authors: Silvestre, Francisco Javier; Márquez-Arrico, Cecilia Fabiana
title: COVID-19 and Periodontitis: A Dangerous Association?
date: 2022-01-13
journal: Front Pharmacol
DOI: 10.3389/fphar.2021.789681
sha: 42a78bebc312f27e641f1ca0ad5ecc7ad6f745ca
doc_id: 942061
cord_uid: v4zhz80s

nan

parameters relevant to the course of COVID-19 such as concentrations of D-dimer, HbA1c, D vitamin, white blood cells, and lymphocytes have been found to be elevated in patients with moderate-advanced periodontitis (Marouf et al., 2021) . In this way, patients with previous periodontitis could be more susceptible to exacerbations of COVID-19 (Marouf et al., 2021) (Figure 1) .

Interestingly, an increase in cytokines in blood samples from patients with moderate or severe COVID-19 has been observed, and this increase in cytokines may be related to a worsening in the evolution of the disease (Marouf et al., 2021) . An increase in blood cytokines has also been detected in patients with chronic periodontitis, and it has been proven that periodontal treatment favors serum reduction of the cytokine levels (Marouf et al., 2021) .

Periodontal inflammation against the background of periodontitis has an overexpression of IL-6 and IL-17. IL-6 is also overexpressed alongside IL-1 when SARS-CoV-2 infects the airway. Over the course of COVID-19, the lethality of interstitial pneumonia has been linked to overproduction of IL-6 and other ILs. Therefore, there could be a link between the low-grade inflammation of advanced periodontitis and the aggravation of COVID-19 in the context of other chronic diseases (diabetes and obesity) (Campisi et al., 2021) . Another mechanism of periodontitis is the so-called extracellular neutrophil entrapment (NETs), which represents an alternative form of cell death and tissue damage through immune mechanisms (Magán-Fernández et al., 2019; Borges et al., 2020; Gupta and Sahni, 2020; Magán-Fernández et al., 2020) . Cell death by NETs can also be stimulated by SARS-CoV-2 (Gupta and Sahni, 2020). Exacerbation of NET production has been observed in advanced stages of COVID-19 and periodontitis, which could hypothesize a certain relationship between the physiopathogenic mechanisms of immune hyperresponse in both diseases (Magán-Fernández et al., 2019; Borges et al., 2020; Gupta and Sahni, 2020; Magán-Fernández et al., 2020) . However, the mechanisms that comprise this association are yet to be determined.

Studies have recently been published where periodontitis has been linked to an increased risk of complications from COVID-19 (Magán-Fernández et al., 2019; Borges et al., 2020; Gupta and Sahni, 2020; Magán-Fernández et al., 2020; Takahashi et al., 2020; Anand et al., 2021; Campisi et al., 2021; Gupta et al., 2021; Larvin et al., 2021) .

It has been speculated that the possible dissemination of periodontopathogenic bacteria inside the lower respiratory tract creates favorable conditions for suffering from the most severe SARS-CoV-2 infection through tissue damage and accelerating the process of cellular senescence at this level, as well as facilitating lung infection. Also, periodontal bacteria could be introduced through endotracheal intubation to which patients with respiratory distress are subjected (Aquino-Martinez and Hernández-Vigueras, 2021).

Besides, hospitalization of patients with periodontitis generates a situation of worsening of their oral health for the following reasons: the lack of oral hygiene in the hospitalized patients generating an increase in bacterial plaque due to the lack of good chemical-mechanical control, intubation of the patients and consequent parenteral feeding, general lack of stimulation of the salivary glands, dry mouth, and alterations in the bacterial flora (Magán-Fernández et al., 2019; Borges et al., 2020; Gupta and Sahni, 2020; Larvin et al., 2020; Magán-Fernández et al., 2020; Aquino-Martinez and Hernández-Vigueras, 2021; Campisi et al., 2021; Gupta et al., 2021; Marouf et al., 2021) . As a conclusion, we can say that COVID-19 has been recently associated with periodontitis in various studies (Magán-Fernández et al., 2019; Borges et al., 2020; Gupta and Sahni, 2020; Larvin et al., 2020; Magán-Fernández et al., 2020; Aquino-Martinez and Hernández-Vigueras, 2021; Campisi et al., 2021; Gupta et al., 2021; Marouf et al., 2021; World Health Organization, 2021) . Among the mechanisms of association between both diseases, we found the inflammatory and infectious nature of both diseases shares the pull of cytokines, ILs, increased CRP, and TNF-α, among others. On the other hand, the entry pathway through the epithelia that expose a higher level of ACE2 receptors in patients with advanced periodontitis, and the increase in D-dimer present in patients with advanced periodontitis could be ways of association between both diseases. In the same way, the increase in ACE2 in periodontitis could be a reason for exacerbation of COVID-19.

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

MA-CF is a recipient of a predoctoral fellowship from the Ministry of Science, Innovation and Universities (FPU18/00854).

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Conflict of Interest: The authors declare that the research was conducted in the