Corona virus disease 19 (COVID 19) risk factors are age, race, gender and preexisting conditions including cardiovascular, respiratory, and endocrine diseases (Wue et al., 2020). The severe acute respiratory corona virus 2 (SARS-CoV-2) binds to the angiotensin- converting enzyme 2 (ACE2) receptor for cellular entry and infects respiratory tract cells (Zou et al., 2020). Multiple organs, including kidneys, lungs, brain, and pharynxes are affected and account for increased morbidity (Puelles et al., 2020). ACE2 receptors are also present on the epithelial cells of oral mucosa, gingiva and alveolar bone, making the oral cavity a reservoir of viruses close to the respiratory tract (Xu et al., 2020). These receptors are downregulated in patients with periodontal disease (PD) (Queiroz-Junior et al., 2019). PD is associated with chronic state of inflammation (Merchant et al., 2016; Van der etal., 2016; Delange et al, 2018), and has been linked to several conditions which are known risk factors for COVID 19 including diabetes, respiratory and cardiovascular diseases (Van der et al., 2016). PD has been implicated as potential risk factor for COVID19 (Pitones-Rubio et al., 2020), however, this was not demonstrated.
We studied the association between COVID 19, periapical dental infection (PA), caries and PD. Using the University of Florida patient’s registry, informatics for integrating biology and the bedside (i2b2), the odds ratio (OR) for COVID 19 infection in patients with oral diseases were assessed using logistic regression model. Because the oral diseases association with risk factors for COVID 19, we adjusted the OR for gender, race, age, smoking status and systemic conditions. The study was exempted from institutional review board (IRB) review as the data did not contain personal health information (PHI)
From a hospital population of 987,849 patients, 889 patients had a confirmed diagnosis of COVID 19. Seven (0.77%) patients were diagnosed with PD, 16 (1.7%) with PA and 31 (3.48%) with caries.
Patients with caries were 3.0 times (95% CI= (2.0, 4.4)) more likely to have COVID 19. The OR from 2.3 to 3.6 after adjusting for gender, age or race compared to caries free patients. Patients with PA were 7.0 times (95% CI= (4.7, 10.4)) more likely to have COVID 19 than people without PA. The adjusted OR from 2.7 to 4.1 after controlling for gender, age, race and a systemic condition one at a time. PD was not associated with Covid-19 status with OR=1.1 95% CI= (0.3, 4.2), however, after adjusting for smoking, patients with PD were 4.7 times more likely to have COVID 19 than patients without PD. African American had increased OR for both PA and caries (Table 1).
Table 1:
Odds ratio for patients with certain oral diseases to develop Covid 19 infection using logistic regression model
| Odds Ratio | 95% Wald Confidence Limits | P Value | ||
|---|---|---|---|---|
| PA vs Non PA (Model PA not adjusted for any covariate) | 7.006 | 4.739 | 10.356 | <.0001 |
| PA vs Non PA | 4.128 | 2.474 | 6.89 | <.0001 |
| Gender Male vs Female (Model of PA adjusted -for gender) | 0.915 | 0.8 | 1.045 | 0.1886 |
| PA vs Non PA | 3.482 | 2.121 | 5.715 | <.0001 |
| Age Group 18–34 vs 0–17 yrs | 5.42 | 3.961 | 7.415 | <.0001 |
| Age Group 35–44 vs 0–17 yrs | 3.531 | 2.482 | 5.025 | 0.0005 |
| Age Group >=45 vs 0–17 yrs (Model of PA adjusted for age) | 2.511 | 1.839 | 3.429 | 0.4317 |
| PA vs Non PA | 2.745 | 1.668 | 4.515 | <.0001 |
| Race Black vs Other | 3.408 | 2.849 | 4.077 | <.0001 |
| Race White vs Other (Model of PA adjusted for race) | 1.291 | 1.104 | 1.51 | <.0001 |
| PA vs Non PA | 2.996 | 2.022 | 4.439 | <.0001 |
| Respiratory disease vs Non Respiratory disease (Model of PA adjusted for Respiratory disease) | 8.372 | 7.295 | 9.606 | <.0001 |
| PA vs Non PA | 1.865 | 1.027 | 3.389 | 0.0407 |
| Any Endocrine diseases vs Non Any Endocrine disease (Model of PA adjusted for Endocrine disease) | 4.348 | 3.808 | 4.963 | <.0001 |
| PA vs Non PA | 0.982 | 0.439 | 2.199 | 0.9298 |
| Obesity vs No Obesity (Model of PA adjusted for obesity) | 5.643 | 4.854 | 6.562 | <.0001 |
| PA vs Non PA | 2.098 | 1.122 | 3.923 | 0.0203 |
| Diabetes vs No Diabetes (Model of PA adjusted for diabetes) | 3.647 | 3.029 | 4.392 | <.0001 |
| PA vs Non PA | 0.703 | 0.315 | 1.572 | 0.3911 |
| Circulatory disease vs Non Circulatory disease (Model of PA adjusted for circulatory disease) | 5.494 | 4.885 | 6.178 | <.0001 |
| PA vs Non PA | 0.218 | 0.082 | 0.581 | 0.0023 |
| Smoked vs Never Smoked (Model of PA adjusted for smoking status) | 0.455 | 0.414 | 0.5 | <.0001 |
| Caries vs Caries Free (Model of Caries not adjusted for any covariate) | 2.981 | 2.031 | 4.374 | <.0001 |
| Caries vs Caries Free | 2.462 | 1.719 | 3.524 | <.0001 |
| Gender Male vs Female (Model of caries adjusted for gender) | 0.889 | 0.778 | 1.016 | 0.084 |
| Caries vs Caries Free | 3.573 | 2.493 | 5.122 | <.0001 |
| Age Group: 18–34 vs 0–17yrs | 6.497 | 4.649 | 9.081 | <.0001 |
| Age Group: 35–44 vs 0–17yrs | 3.954 | 2.718 | 5.751 | 0.0013 |
| Age Group:>=45 vs 0–17yrs (Model of caries adjusted for age) | 3.077 | 2.205 | 4.295 | 0.6131 |
| Caries vs Caries Free | 2.328 | 1.618 | 3.348 | <.0001 |
| Race Black vs Other | 3.265 | 2.729 | 3.905 | <.0001 |
| Race White vs Other (Model of caries adjusted for race) | 1.238 | 1.06 | 1.447 | <.0001 |
| Caries vs Caries Free | 1.22 | 0.83 | 1.794 | 0.3117 |
| Respiratory disease vs Non Respiratory disease (Model of caries adjusted for Respiratory disease) | 8.73 | 7.593 | 10.037 | <.0001 |
| Caries vs Caries Free | 1.418 | 0.918 | 2.19 | 0.1153 |
| Any Endocrine vs Non Any Endocrine Disease (Model of caries adjusted for endocrine disease) | 4.393 | 3.846 | 5.018 | <.0001 |
| Caries vs Caries Free | 1.614 | 1.054 | 2.472 | 0.0277 |
| Obesity vs Non Obesity (Model of caries adjusted for Obesity) | 5.681 | 4.889 | 6.603 | <.0001 |
| Caries vs Caries Free | 3.299 | 2.347 | 4.635 | <.0001 |
| Diabetes vs Non Diabetes (Model of caries adjusted for Diabetes) | 3.558 | 2.956 | 4.283 | <.0001 |
| Caries vs Caries Free | 1.374 | 0.849 | 2.225 | 0.1963 |
| Circulatory Disease vs Non Circulatory Disease (Model of caries adjusted for Circulatory disease) | 3.173 | 2.766 | 3.64 | <.0001 |
| Caries vs Caries Free | 3.469 | 2.432 | 4.948 | <.0001 |
| Smoked vs Never Smoked (Model of caries adjustedby smoking status) | 1.032 | 0.874 | 1.218 | 0.713 |
| PD vs Non PD (Model of PD without adjusted for any covariate) | 1.05 | 0.262 | 4.204 | 0.945 |
| PD vs Non PD | 1.038 | 0.43 | 2.504 | 0.9345 |
| Respiratory disease vs Non Respiratory disease (Model of PD adjusting for Respiratory disease) | 8.613 | 7.5 | 9.892 | <.0001 |
| PD vs Non PD | 1.927 | 0.86 | 4.318 | 0.1109 |
| Any Endocrine vs Non Any Endocrine Disease (Model of PD adjusted for Endocrine disease) | 4.221 | 3.697 | 4.818 | <.0001 |
| PD vs Non PD | 1.838 | 0.821 | 4.117 | 0.139 |
| Obesity vs Non Obesity (Model of PD adjusted for Obesity) | 5.58 | 4.804 | 6.483 | <.0001 |
| PD vs Non PD | 1.979 | 0.819 | 4.78 | 0.1294 |
| Diabetes vs Non Diabetes (Model of PD adjusted for diabetes) | 3.617 | 3.001 | 4.36 | <.0001 |
| PD vs Non PD | 0.671 | 0.167 | 2.693 | 0.574 |
| Circulatory disease vs Non Circulatory disease (Model of PD adjusted for Circulatory disease) | 3.106 | 2.709 | 3.56 | <.0001 |
| PD vs Non PD | 4.673 | 2.323 | 9.4 | <.0001 |
| Smokers vs Never Smoked (Model of PD adjusted for smoking status) | 0.97 | 0.818 | 1.15 | 0.7258 |
PA periapical dental abscesses
PD periodontal disease
The present cross sectional study cannot be interpreted in the context of causality but can estimate the prevalence of the outcome of interest for a given population including exposure to risk factors at a specific point of time (Levin, 2006). Because the oral infection had preceded COVID 19 with reference to this study population, we suggest that oral diseases may play a role in susceptibility or transmission of SARS-CoV-2.
Acknowledgement
We acknowledge the University of Florida Integrated Data Repository (IDR) and the UF Health Office of the Chief Data Officer for providing the analytic data set for this project. Additionally, the Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under University of Florida Clinical and Translational Science Awards UL1 TR000064 and UL1TR00142
Footnotes
Conflict of interest statement: No conflicts
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