COVID‐19 is associated with an exacerbated inflammatory response that can result in fatal outcomes. Systemic inflammation is also a main characteristic of periodontitis. Therefore, we investigated the association of periodontitis with COVID‐19 complications.
A case–control study was performed using the national electronic health records of the State of Qatar between February and July 2020. Cases were defined as patients who suffered COVID‐19 complications (death, ICU admissions or assisted ventilation), and controls were COVID‐19 patients discharged without major complications. Periodontal conditions were assessed using dental radiographs from the same database. Associations between periodontitis and COVID 19 complications were analysed using logistic regression models adjusted for demographic, medical and behaviour factors.
In total, 568 patients were included. After adjusting for potential confounders, periodontitis was associated with COVID‐19 complication including death (OR = 8.81, 95% CI 1.00–77.7), ICU admission (OR = 3.54, 95% CI 1.39–9.05) and need for assisted ventilation (OR = 4.57, 95% CI 1.19–17.4). Similarly, blood levels of white blood cells, D‐dimer and C Reactive Protein were significantly higher in COVID‐19 patients with periodontitis.
Periodontitis was associated with higher risk of ICU admission, need for assisted ventilation and death of COVID‐19 patients, and with increased blood levels of biomarkers linked to worse disease outcomes.
This study identified that the risk of COVID‐19 complications was significantly higher among patients with moderate‐to‐severe periodontitis compared to those with milder or no periodontitis. Periodontitis shares common risk factors with most chronic inflammatory diseases known to influence COVID‐19 severity (Ruan et al., 2020; Zhou et al., 2020); thus, we performed multivariate logistic regression modelling to adjust this association for possible confounders such as age, sex, and smoking behaviour, and for comorbidities (diabetes, hypertension, etc.). After adjustment, periodontitis still had a significant impact on the course of COVID‐19 infection, with significant associations COVID 19 complications (OR = 3.67, 95% CI 1.46–9.27), death (OR =8.81, 95% CI 1.00–77.7), ICU admission (OR = 3.54, 95% CI 1.39–9.05) and need for assisted ventilation (OR = 4.57, 95% CI 1.19–17.4). These compelling results further confirm the association between periodontitis and worse progression of COVID‐19.
Periodontitis has been shown to affect systemic health in multiple studies (Monsarrat et al., 2016) and has been independently associated with increased risk of most chronic NCDs (Genco & Sanz, 2020), in particular cardiovascular diseases (Tonetti & Van Dyke, 2013; LaMonte et al., 2017; Sanz et al., 2020); diabetes (Chapple et al., 2013; Suvan et al., 2015; Sanz et al., 2018); hypertension (Munoz Aguilera et al., 2020); chronic renal disease (Sharma et al., 2016), pneumonia (Gomes‐Filho et al., 2020) and cancer (Nwizu et al., 2020).
Furthermore, a recent systematic review of 57 studies with 5.71 million participants reported the association of periodontitis with increased risk of mortality, specifically, in association with CVD, cancer, CHD and cerebrovascular diseases (Romandini et al., 2020). These associations have been explained, by shared genetic and environmental risk factors, and also through common chronic inflammatory pathways (Schenkein et al., 2020).
Several hypothetical mechanisms may explain the strong associations observed between periodontitis and COVID‐19 severity. Takahashi et al suggested that aspiration of periodontopathic bacteria might aggravate COVID‐19 by inducing the expression of angiotensin‐converting enzyme 2, a receptor for SARS‐CoV‐2, and inflammatory cytokines in the lower respiratory tract (Takahashi et al., 2020). Also, it was suggested that periodontopathic bacteria might enhance SARS‐CoV‐2 virulence by cleaving its S glycoproteins (Madapusi Balaji et al., 2020; Takahashi et al., 2020) and that the oral cavity, and specially periodontal pockets could act as a viral reservoir (Badran et al., 2020; Bao et al., 2020; Botros et al., 2020; Herrera et al., 2020; Kheur et al., 2020). Gupta et al indicated that Neutrophil Extracellular Trap production is involved in the pathogenesis of both diseases (Gupta & Sahni, 2020), and Sahni et al suggested that the strong Th17 response in severe periodontitis could exacerbate the cytokine storm in COVID‐19 (Sahni & Gupta, 2020). All these hypothetical pathways could also foresee an increased incidence of periodontal lesions, especially necrotizing periodontal disease (NPD) during this pandemic (Patel & Woolley, 2020).
In our study, fatal COVID‐19 outcomes were significantly associated with higher blood concentrations of D‐dimer, WBC and CRP, and lower concentrations of lymphocytes. Also, patients admitted to the ICU as well as those requiring assisted ventilation presented high blood levels of CRP and D‐dimer. These results are in agreement with previous studies reporting elevated inflammatory indicators in deceased COVID‐19 patients (Ruan et al., 2020). Interestingly, our COVID‐19 cases with periodontitis also had significantly higher WBC and CRP serum levels than those without periodontitis, which may indicate a possible link of this association through systemic inflammation.
Successful treatment of periodontitis has been shown to improve serum markers of systemic inflammation (CRP, IL‐6) (D'Aiuto et al., 2013), as well as systemic metabolic control (Montero et al., 2020). If a causal link is established between periodontitis and increased rates of adverse outcomes in COVID‐19 patients, then establishing and maintaining periodontal health may become an important part of the care of these patients.
This cross‐sectional study has clear limitations, and the results need to be taken with caution. It does not address causality, and even though we adopted the new classification for staging Periodontitis (Papapanou et al., 2018), using only one of the parameters (interdental bone loss) may limit the diagnostic accuracy. Nonetheless, this was mitigated by blinded assessment of the radiographs by independent examiners. Regarding statistical power, a representative sample was recruited, based on all COVID‐19 cases registered in the country from the beginning of the COVID‐19 pandemic, which also reduced selection bias.
Future research, including interventional studies focused on the influence of periodontitis and periodontal treatments on COVID‐19 infections, would help better understand the causal connections between them. Furthermore, understanding the mechanisms underpinning the relationship between periodontitis and COVID‐19 complications is a promising area of research that may produce mechanistic targets, risk stratification and novel interventions.
Periodontitis was significantly associated with a higher risk of complications from COVID‐19, including ICU admission, need for assisted ventilation and death and increased blood levels of markers linked worse COVID‐19 outcome such as D‐dimer, WBC and CRP.
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