key: cord-1039860-5tnvdlb6
authors: Espinoza-Espinoza, Daniel Alonso Kim; Dulanto-Vargas, Julissa Amparo; Cáceres-LaTorre, Oswaldo Andreé; Lamas-Castillo, Fiorella Estefanie; Flores-Mir, Carlos; Cervantes-Ganoza, Luis Adolfo; López-Gurreonero, Carlos; Ladera-Castañeda, Marysela Irene; Cayo-Rojas, César Félix
title: Association Between Periodontal Disease and the Risk of COVID-19 Complications and Mortality: A Systematic Review
date: 2021-11-30
journal: J Int Soc Prev Community Dent
DOI: 10.4103/jispcd.jispcd_189_21
sha: 72cca1201ed8b18f798919e4fcf8b2b00b35e06d
doc_id: 1039860
cord_uid: 5tnvdlb6

AIM: The COVID-19 pandemic has strained the world’s healthcare systems. Studies have identified how the COVID-19 infections are linked to several co-morbidities such as hypertension, diabetes, cardiovascular disease, renal and pulmonary disease. It is known that periodontal disease (PD) shares the same risk factors. Moreover, both diseases are characterized by an exaggerated immune response. The aim of the study was to investigate the available evidence of a potential association between PD and the risk of COVID-19 complications and mortality. MATERIALS AND METHODS: MEDLINE/PubMed, EMBASE, Scopus, and ProQuest were searched. Studies that assess the association between PD and the risk of COVID-19 complications and mortality were eligible for inclusion. Two independent reviewers performed the selection of articles and data extraction. The New Castle Ottawa Scale was used to assess the quality of the selected studies, and the GRADE system was used to evaluate the level of confidence to support the conclusions. RESULTS: Only two studies met the eligibility criteria. One study had a low risk of bias, whereas the other had a high risk of bias. CONCLUSION: The level of confidence in the available evidence is very low. A close association between periodontitis and the risk of COVID-19 complications and mortality can neither be supported nor refuted.

Health Organization (WHO). [1] It is estimated that more than 4.5 million people were infected during the first 3 months. Meanwhile, this infectious disease continues spreading quickly around the world. [2] The SARS-CoV-2 is transmitted mainly through respiratory droplets during near face-to-face contact. This infection can spread through asymptomatic, pre-symptomatic, or symptomatic carriers. [3] The COVID-19 manifestations include asymptomatic carriers and sometimes a fulminant disease progression characterized by sepsis and acute respiratory insufficiency. About 5% of all patients with COVID-19 and 20% of hospitalized patients experience severe symptoms requiring intensive care. [4] Between 17% and 35% of the hospitalized patients with COVID-19 are treated more frequently in an intensive care unit (ICU) due to hypoxemic respiratory insufficiency. For patients treated in ICU due to COVID-19, it is estimated that between 29% and 91% require invasive mechanical ventilation. [5] [6] [7] [8] [9] Hospitalized patients, besides having respiratory insufficiency, can develop acute renal insufficiency (9%), hepatic dysfunction (19%), septic shock (6%), and coagulation dysfunction or hemorrhage (10-25%). [4] Regarding the mortality, in a cohort of 3988 patients in critical conditions due to SARS-CoV-2 infection, the estimated rates of mortality per 1000 patient-days were 27 (CI of 95%, [26] [27] [28] [29] in the hospital and 12 (CI of 95%, [11] [12] in the ICU. In the subset of the first 1715 patients, the mortality was 48.8% in ICU and 53.4% in-hospital conditions. [10] COVID-19 is more prevalent in patients who suffer from co-morbidities such as hypertension (present in 48-57% of the patients), diabetes (17-34%), cardiovascular disease (21-28%), chronic pulmonary disease (4-10%), chronic renal disease (3-13%), malignant neoplasm (6-8%), and chronic hepatic disease (<5%). [4] Periodontitis or periodontal disease (PD) is a chronic inflammatory disease caused by microorganisms and characterized by the progressive destruction of the support apparatus of the tooth that can lead to tooth loss. [11] Recent studies suggest that PD could be associated with COVID-19 complications and mortality. [11, 12] PD and COVID-19 present two common characteristics: (1) risk factors such as hypertension, diabetes, cardiovascular disease, and renal and pulmonary disease [4, [13] [14] [15] [16] [17] and (2) exaggerated immune response characterized by a high release of interferons, interleukins (ILs), tumor necrosis factor (TNF), chemokines, and tissue damage in the more severe presentation of these two diseases. [18] [19] [20] [21] [22] Due to the importance and prevalence of both diseases nowadays, the purpose of this review was to evaluate the available evidence about a potential association between PD and the risk of COVID-19 complications.

The protocol for this systematic review was registered in the database of PROSPERO with the code CRD42021244289

(https://www.crd.york.ac.uk/ PROSPERO/display_record.php?RecordID=244289).

This review was written and conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses). [23] Study selection The initial selection of the articles was carried out independently by two reviewers (D.A.K.E.-E. and O.A.C.-L.) according to the title and abstract. If the abstract was not available, the full text was obtained and evaluated. The full text of all articles was compiled, and the inclusion criteria were verified. Any disagreement was solved by consensus or by the decision of a third author (C.F.C.-R.). The articles that did not meet the selection criteria were excluded from the review, and reasons for exclusion were registered. The description of the selected studies can be seen in Tables 2 and 3 .

The researchers (D.A.K.E.-E., O.A.C.-L. and C.F.C.-R.) also performed the quality assessment of all the studies; the information was compared, and a consensus was made. To assess the quality of the selected studies, the Quality Access Scale-Newcastle-Ottawa Scale instrument was used. [17, 25] This scale assigns a maximum of 9 points to each study: 4 for exposure selection and assessment, 2 for comparability, and 3 for outcome assessment. If a study receives a score of ≥ 6, it is considered a publication with a low risk of bias [ Table 4 ].

Quality of evidence of the present study-grade system The GRADE system [26] was used to evaluate the certainty of the evidence. It considers five items that may downgrade its certainty: risk of bias, inconsistency, indirect evidence, imprecision, and publication bias. The evidence certainty levels may be scored as follows: high, moderate, low, and very low [ Table 5 ].

The electronic search procedure is presented in Figure 1 . A total of 303 studies were initially identified from the electronic databases. After that, 158 duplicate studies were eliminated. Then, titles and abstracts were evaluated, and 143 articles were excluded. No additional studies were found from the hand search of pre-publication manuscripts. Finally, only two articles were included. ("periodontitis"/exp OR "periodontitides":ti,ab,kw OR "pericementitis":ti,ab,kw OR "pericementitides":ti,ab,kw OR "periodontal disease"/exp OR "disease, periodontal":ti,ab,kw OR "diseases, periodontal":ti,ab,kw OR "periodontal diseases":ti,ab,kw OR "parodontosis":ti,ab,kw OR "parodontoses":ti,ab,kw OR "pyorrhea alveolaris"/exp OR "gingivitis"/exp OR "gingivitides":ti,ab,kw) AND ("coronavirus"/exp OR "coronavirus covid-19"/exp OR "novel coronavirus"/exp OR "SARS-CoV"/exp OR "sars cov-2"/exp OR "covid-19"/exp OR "SARS-CoV-2"/exp OR "SARS-CoV"/exp OR "MERS-CoV"/exp OR "2019-nCoV"/ exp) SCOPUS (23.07.2021) n= 156 TITLE-ABS-KEY((periodontitis OR periodontitides OR pericementitis OR pericementitides OR periodontal OR "Diease, Periodontal" OR "Diseases, Periodontal" OR "Periodontal Disease" OR parodontosis OR parodontes OR "Pyorhea Alveolaris" OR gingivitis OR gingivitides) AND (coronavirus OR "coronavirus covid-19" OR "novel coronavirus" OR "SARS-CoV" OR "sars cov-2" OR "covid-19" OR "SARS-CoV-2" OR "SARS-CoV" OR "MERS-CoV" OR "2019-nCoV")) PROQUEST (23.07.2021) n=17 ("periodontitis" OR "periodontal" OR "periodontal disease" OR "periodontal disease risk" OR "periodontal bacteria" OR "periodontal pocket" OR "apical periodontitis" OR "gingivitis" OR "bleeding gum" OR "gum disease" OR "gingival disease" OR "gingival inflammation") AND ("coronavirus" OR "coronavirus covid-19" OR "novel coronavirus" OR "SARS-CoV" OR "sars cov 2" OR "covid-19" OR "sars cov 2" OR "SARS-CoV" OR "MERS-CoV" OR "2019-nCoV") Filters:subjet periodontitis (a) control unexposed, (b) case unexposed, (c) control exposed, (d) case exposed, COR = crude odds ratio, AOR = adjusted odds ratio, AC = any complication, CI = confidence interval, PD = periodontal disease, (*) adjusted to principal covariables by age, sex, diabetes, co-morbidity, smoking behavior, D = death, ICU = intensive care unit, NAV = need for assisted ventilation, PT = positive test, HA = hospital admission One of the two included studies was published in a dental journal [11] and the other in a medical journal. [12] The sample size varied between 568 patients from Qatar [11] and 13,502 from the UK, [12] with a similar proportion in female and male participants. Regarding the methodological aspects, one was a retrospective case-control [11] and the other a nested case-control. [12] Both studies used national database records. Table 2 provides a summary of the general characteristics of the two included studies.

The characteristics of the study groups were extracted and calculated from the results study tables according to types of exposure of periodontal variables. The cases included definitions such as mortality, [11, 12] need for ventilation assistance, [11] ICU, [11] and hospital admission. [12] All periodontal variables were indirectly classified through bone loss as suggested from radiographs [11] or participants' self-reports of bleeding and tooth loss. [12] Inferential results on the association of COVID-19 and periodontitis were given in crude and adjusted odds ratios. More information on the studies' results can be found in Table 3 .

The two selected studies had a case-control design; therefore, the critical appraisal verification was carried out concerning eight items for this design (Newcastle-Ottawa Scale). All the items had a score value of one, except the item "comparability of cases and controls based on the design and analysis," which presented a double score value. Larvin et al.'s [12] studies obtained a score of 5, corresponding to a low-quality evidence publication and a high risk of bias. In contrast, Marouf et al.'s [11] studies obtained a score of 7, which gives the article a high evidence quality value. None of the studies had a score for the item "non-response rate." Larvin et al.'s study did not receive any score on adequate case definition, nor ascertainment of exposure [ Table 4 ].

The evaluation for quality of evidence using the GRADE system for studies related to the association between PD and the risk of complications and mortality COVID-19 resulted in very low overall certainty [ Table 5 ].

This systematic review aimed to explore the most recent scientific evidence on the association between PD and the risk of COVID-19 complications and mortality. The current literature on COVID-19 is increasing exponentially. Due to its pandemic nature, it seems important to investigate other possible risk factors. PD has recently been reported as a potential risk factor for higher mortality from COVID-19. [11, 12] The reports indicate that the connection is based on the oral viral load or by cytokines, which have a fundamental role in the immune-inflammatory response to infections, including periodontal pathogens. [7, 22, 23] Although currently these are only hypothetical mechanisms, they present a plausible biological explanation. Previous studies hinted at a probable relation between them. Therefore, the present systematic review aimed to review the available evidence on the association between PD and the risk of COVID-19 complications and mortality.

Only two observational studies met the eligibility criteria of this systematic review, and these were two national multicenter studies from Qatar [11] and the UK. [12] Although these studies do not represent patients from different parts of the world, national records provide epidemiological value on diseases and/ or conditions in each country with a lower selection bias. According to the Oxford Center for Evidence-Based Medicine (CEBM), the quality of the evidence concerning the type of study indicates a level 3b for both investigations. [27] The reason for excluding most of the articles was mainly the deficiency or absence of information related to the exposure of periodontitis and results.

Considering the results of the included studies, one of them found a positive association between periodontitis and COVID-19. [11] This study showed statistically significant adjusted results of high probabilities and confidence intervals (CIs) of total complications due to COVID- 19 , and clinical parameters of blood levels of white blood cells, D-dimer, and C-reactive protein (CRP) (P < 0.01). The adjusted data controlled probable confounding factors such as smoking, co-morbidities, and individual characteristics such as sex/gender and age. Nonetheless, the study is compromised by potential inherent biases due to the retrospective nature of the design and how PD was diagnosed. The methodological evaluation of PD measurement used the concept of radiographic bone loss percentage [28] and its grouping according to periodontal stages. [29] The absence of clinical parameters such as probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), plaque index (PI), and tooth loss limits the diagnostic interpretation of PD.

Further, they evaluated biomarkers such as D-dimer, CRP, HbA1c, vitamin D, white blood cells, and lymphocytes. This information is of interest to indirectly evaluate PD and the link between PD and COVID-19 complications as they present immunological, microbiological, and biochemical expressions.

However, the coexistence of both diseases linked to the production of inflammatory biomarkers is a source of potential bias for data interpretation.

The negative association of variables from the study carried out in the UK is likely a consequence of its solid sample size of 13,253 participants. [12] The sample is based on a cohort of national data records considered representative of the country. This is an important methodological feature when selecting controls. The statistics were not conclusive concerning PD and COVID-19 as the result of the applied multivariate regression was less than 1, except the probability of mortality in cases of bleeding or painful gums [OR = 1.71; 95% CI (1.05-2.72)]. As in the study mentioned before, confounding factors and socioeconomic variables and ethnicity were controlled. The study authors reported underestimating cases as a relevant weakness; this could be explained by the short period the patients stayed in the hospital or the number of deaths. In that sense, the PD cases could have been underestimated in the selection. Perhaps, the most relevant weakness of the study is related to the diagnosis of PD, which was self-reported by the participants regarding pain and/or bleeding of the gums and tooth loss. The reliability of the data is biased in that sense as no clinical/radiological evaluation was performed. Finally, the information did not filter previous periodontal treatments, which could have underestimated the identification of PD.

The risk of bias found using the Newcastle-Ottawa scale showed that even though the study by Marouf et al. had weakness in the way PD had been determined, the case definition was extracted from valid records. [28, 29] In contrast, the study by Larvin et al. used self-report to determine the cases, which does not represent a reliable source for an adequate clinical case definition, nor is it a reliable method of ascertainment of cases and controls. [12, 30] As the non-response rate had not been specified, none of the studies received any score in this item.

Regarding the possible theoretical explanation between PD and the risk of COVID-19 complications and mortality, there is evidence that supports this hypothesis, such as the association between periodontitis and other systemic diseases such as diabetes, cardiovascular disease, adverse pregnancy outcomes, rheumatoid arthritis, chronic obstructive pulmonary disease, inflammatory bowel disease, and chronic kidney disease. [31] [32] [33] [34] COVID-19 virus infects human cells by binding the viral spike protein (S) with angiotensinconverting enzyme 2 (ACE 2), a cellular receptor highly expressed in type II pneumocytes, macrophages, endothelial cells, and other lung cells. [35] [36] [37] This binding triggers the production of inflammatory cytokines capable of inducing intravascular coagulopathy and thrombotic complications in pulmonary blood vessels. [35, 36, 38, 39] Although it mainly affects the lungs, the SARS-CoV-2 virus also affects the cardiovascular [11] * * * * * * * 7/9

Larvin et al.

(2020) [12] * * * * * 5/9 Records excluded as duplicates (n = 186) Figure 1 : Summary of the selection process of the studies related to the association between periodontitis and the risk of complications and mortality for COVID -19 system. The vasculature is affected in COVID-19, both directly by the SARS-CoV-2 virus and indirectly due to a storm of systemic inflammatory cytokines. This includes the role of vascular endothelium in the recruitment of inflammatory leukocytes where they contribute to the tissue damage and the release of cytokines, which are key drivers of acute respiratory distress syndrome, in disseminated intravascular coagulation and cardiovascular complications in COVID-19. [40] In patients who develop the most severe forms of COVID-19, there is a high incidence of macro-and microvascular thrombosis, prolonged hospitalization, and risk of death. This is attributed to a "cytokine storm," with elevated serum levels of inflammatory cytokines (IL-6, IL-1, IFN-γ) and endothelial activation markers such as von Willebrand factor, coagulation factor 8, and P-soluble selectin, resulting in endothelialitis and microvascular thrombosis. [41] [42] [43] Del Valle et al. [44] identified high serum levels of IL-6 and TNF-α when the progression of the disease required the patient to be hospitalized. Moreover, it has been suggested that age-related drop in host's immunity (immunosenescence) combined with a low-grade chronic systemic inflammation predisposes patients to further complications when infected with SARS-CoV-2. [45, 46] In addition to severe injury to local tissues, there are systemic consequences such as direct lung injury, acute respiratory distress syndrome, multiple organ failure, and unfavorable prognosis. [47] [48] [49] Likewise, it has been reported that in severe cases of COVID-19, the leading cause of death is respiratory failure associated with excessive inflammation. [50] It has been described that the aspiration of periodontal pathogens could increase the severity of the infection of the lungs by SARS-CoV-2. [51] Besides, it has been reported that aspiration of saliva with a high viral load can transport the virus to the lower respiratory tract, increasing the risk of developing more severe forms of the disease. [52] On the contrary, it is mentioned that inflamed periodontal tissues would act as a reservoir of proinflammatory cytokines (TNF-α, IL-1 α, IL-1 β and IL-6) that could be systemically disseminated through the blood circulation, exacerbating the preexisting systemic inflammation. [53] [54] [55] Furthermore, the infection of alveolar epithelial cells by SARS-COV-2 generates an active acute inflammatory response to macrophages, B and T lymphocytes for the release of pro-inflammatory cytokines. These inflammatory factors induce large amounts of inflammatory exudate and red blood cells to enter the pulmonary alveoli, resulting in dyspnea, respiratory failure, and death. [56] [57] [58] This would explain the findings of a significant presence of microthrombi and vascular injury in post-mortem reports of patients with COVID-19. [59] Another association mechanism between periodontitis and COVID-19 is the effect of prolonged exposure to Porphyromonas gingivalis lipopolysaccharides and other periodontal pathogens. These bacterial products produce accelerated senescence of different types of cells, including the pulmonary epithelial cells. This effect facilitates the entry and promotes the viral replication of SARS-CoV-2. [60] In contrast, Shivshankar et al. [61] showed that senescent cells promote bacterial adhesion to lung cells, eventually resulting in increased susceptibility to bacterial-induced pneumonia in older adults.

Additionally, PD has been associated with various factors and co-morbidities such as diabetes, obesity, advanced age, and high blood pressure; likewise, these factors have also been associated with the progression or severity of COVID-19. Since inflammatory factors seem to play an important role affecting systemically both PD and COVID-19, it is possible to think that periodontal status can be considered a risk indicator for complications of COVID-19. [62, 63] However, in view of the statement that PD and COVID-19 present two common characteristics: (1) risk factors such as hypertension, diabetes, cardiovascular disease, and renal and pulmonary disease [4, [13] [14] [15] [16] [17] and (2) exaggerated immune response characterized by a high release of interferons, ILs, TNF, chemokines, and tissue damage in the more severe presentation of these two diseases, [18] [19] [20] [21] [22] one wonders how a potential association between PD and the risk of COVID-19 complications could/should be interpreted.

The available evidence does not conclusively support an association between periodontitis and the risk of complications and mortality from COVID-19. However, the findings obtained by the studies included in this review suggest that this association may be feasible. More research is needed to minimize methodological and clinical heterogeneity between studies, particularly regarding the characteristics of the samples and the definition of the most relevant results. Additionally, various biological mechanisms could be considered as factors supporting the association between both diseases.

In addition, both periodontitis and the risk of complications such as hospitalization, ICU admission, the need for assisted ventilation, and mortality from COVID-19 are public health concerns in this pandemic. These findings could also suggest the need for additional actions to implement prevention measures and promote oral health in people who suffer from periodontitis and have risk factors such as hypertension, diabetes, cardiovascular disease, kidney disease, and lung disease.

The level of confidence in the available evidence is very low. A close association between periodontitis and the risk of COVID-19 complications and mortality can neither be supported nor refuted.

who-announces-covid-19-outbreak-a-pandemic

PregCOV-19 Consortium. Clinical manifestations, prevalence, risk factors, outcomes, transmission, diagnosis and treatment of COVID-19 in pregnancy and postpartum: A living systematic review protocol

COVID-19 Systematic Urgent Review Group Effort (SURGE) Study Authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: A systematic review and meta-analysis

Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): A review

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area

Features of 20133 UK patients in hospital with Covid-19 using the ISARIC WHO Clinical Characterisation Protocol: Prospective observational cohort study

COVID-19 Lombardy ICU Network. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy

Characteristics of hospitalized adults with COVID-19 in an integrated health care system in California

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study

COVID-19 Lombardy ICU Network. Risk factors associated with mortality among patients with COVID-19 in intensive care units in

Association between periodontitis and severity of COVID-19 infection: A case-control study

The impact of periodontal disease on hospital admission and mortality during COVID-19 pandemic

Periodontitis is associated with hypertension: A systematic review and meta-analysis

Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology

The link between periodontitis/peri-implantitis and cardiovascular disease: A systematic literature review

Association between periodontitis and chronic kidney disease: Systematic review and meta-analysis

Periodontitis and respiratory diseases: A systematic review with meta-analysis

Is a "cytokine storm" relevant to COVID-19?

Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19

Inflammatory mediators in periodontal pathogenesis

Understanding resolution of inflammation in periodontal diseases: Is chronic inflammatory periodontitis a failure to resolve?

COVID-19 & periodontitis: The cytokine connection

Preferred reporting items for systematic reviews and metaanalyses: The PRISMA statement

Identifying the PECO: A framework for formulating good questions to explore the association of environmental and other exposures with health outcomes

Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses

GRADE Working Group. Grading quality of evidence and strength of recommendations

Oxford Center for Evidence Based Medicine. The Oxford Levels of Evidence 2

Reliability of marginal bone level measurements on digital panoramic and digital intraoral radiographs

Staging and grading of periodontitis: Framework and proposal of a new classification and case definition

Validity of self-reported periodontal disease: A systematic review and meta-analysis

Manifesto for a paradigm shift: Periodontal health for a better life

The link between periodontitis and rheumatoid arthritis: A periodontist's perspective

Working Group 3 of the Joint EFP/AAP Workshop. Periodontitis and adverse pregnancy outcomes: Consensus report of the Joint EFP/AAP Workshop on periodontitis and systemic diseases

Association between PD and the risk of COVID-19 complications and mortality 34. Tonetti MS, Van Dyke TE; Working Group 1 of the Joint EFP/AAP Workshop. Periodontitis and atherosclerotic cardiovascular disease: Consensus report of the Joint EFP/ AAP Workshop on periodontitis and systemic diseases

Endothelial cell dysfunction: A major player in SARS-CoV-2 infection (COVID-19)?

COVID-19-associated coagulopathy: An exploration of mechanisms

Confronting the controversy: Interleukin-6 and the COVID-19 cytokine storm syndrome

Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia

Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: Relation to the acute lung injury and pathogenesis of SARS

Endothelial dysfunction in COVID-19: A position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science

Yale IMPACT Team. Longitudinal analyses reveal immunological misfiring in severe COVID-19

Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19

Endotheliopathy in COVID-19-associated coagulopathy: Evidence from a single-centre, cross-sectional study

An inflammatory cytokine signature predicts COVID-19 severity and survival

SARS-CoV-2, immunosenescence and inflammaging: Partners in the COVID-19 crime

Severe COVID-19 lung infection in older people and periodontitis

The pathogenesis and treatment of the 'cytokine storm' in COVID-19

Into the eye of the cytokine storm

Cytokine storm induced by SARS-CoV-2

Clinical features of 85 fatal cases of COVID-19 from Wuhan. A retrospective observational study

Aspiration of periodontopathic bacteria due to poor oral hygiene potentially contributes to the aggravation of COVID-19

Clinical significance of a high SARS-CoV-2 viral load in the saliva

Periodontal pathogens as risk factors of cardiovascular diseases, diabetes, rheumatoid arthritis, cancer, and chronic obstructive pulmonary disease-Is there cause for consideration? Microorganisms

Clinical improvement following therapy for periodontitis: Association with a decrease in IL-1 and IL-6

Distal consequences of oral inflammation

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19

Analysis of cellular senescence induced by lipopolysaccharide in pulmonary alveolar epithelial cells

Cellular senescence increases expression of bacterial ligands in the lungs and is positively correlated with increased susceptibility to pneumococcal pneumonia

Is periodontal disease a risk factor for severe COVID-19 illness?

Review of the clinical characteristics of coronavirus disease 2019 (COVID-19)