The Mouth-COVID Connection: Il-6 Levels in Periodontal Disease — Potential Role in COVID-19-Related Respiratory Complications

REFERENCES

• Sohrabi C, et al. World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19). Int J Surg 2020 Apr;76:71–76. doi: 10.1016/j.ijsu.2020.02.034.
   PubMed Web of Science ®Google Scholar
• Zhou F, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020 Mar;395(10229):P1054–1062. doi: 10.1016/S0140-6736(20)30566-3.
   PubMed Web of Science ®Google Scholar
• Velazquez-Salinas L, Verdugo-Rodriguez A, Rodriguez LL, Borca MV. The role of interleukin 6 during viral infections. Front Microbiol 2019 May;10:1057. doi: 10.3389/fmicb.2019.01057.
   PubMed Web of Science ®Google Scholar
• Herold T, et al. Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients. J Allergy Clin Immunol 2020 Jul;146(1):128–136.e4. doi: 10.1016/j.jaci.2020.05.008.
   PubMed Web of Science ®Google Scholar
• Mehta P, et al. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020 Mar;395(10229):P1033–1034. doi:10.1016/S0140-6736(20)30628-0.
   PubMed Web of Science ®Google Scholar
• Coulthard P. Dentistry and coronavirus (COVID-19) — moral decision-making. Br Dent J 2020 Apr;228(7):503–505. doi:10.1038/s41415-020-1482-1.
   PubMed Web of Science ®Google Scholar
• Irwin C, Myrillas T. The role of IL-6 in the pathogenesis of periodontal disease. Oral Dis 2008 Mar;4(1):43–47. doi:10.1111/j.1601-0825.1998.tb00255.x.
   Google Scholar
• Reis C, et al. Clinical improvement following therapy for periodontitis: Association with a decrease in IL-1 and IL-6. Exp Ther Med 2014 Jul;8(1):323–327. doi:10.3892/etm.2014.1724.
   PubMed Web of Science ®Google Scholar
• Zhou SY, Duan XQ, Hu R, Ouyang XY. Effect of nonsurgical periodontal therapy on serum levels of TNF-a, IL-6 and C-reactive protein in periodontitis subjects with stable coronary heart disease. Chin J Dent Res 2013;16(2):145–151.
   Google Scholar
• Hobbins S, Chapple I, Sapey E, Stockley R. Is periodontitis a comorbidity of COPD or can associations be explained by shared risk factors/behaviors? Int J Chron Obstruct Pulmon Dis 2017 May;12:1339–1349. doi:10.2147/COPD.S127802.
   PubMed Web of Science ®Google Scholar
• White DB, Lo B. A framework for rationing ventilators and critical care beds during the COVID-19 pandemic. JAMA 2020 Mar;323(18):1773–1774. doi:10.1001/jama.2020.5046.
   PubMed Web of Science ®Google Scholar
• Kramer CD, Genco CA. Microbiota, immune subversion and chronic inflammation. Front Immunol 2017;8:255. doi:10.3389/fimmu.2017.00255.
   PubMed Web of Science ®Google Scholar
• Gemmell E, Marshall RI, Seymour GJ. Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontol 2000 1997 Jun;14(1):112–143. doi:10.1111/j.1600-0757.1997.tb00194.x.
   PubMedGoogle Scholar
• Pan W, Wang Q, Chen Q. The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci 2019 Nov 5;11(3):1–13. doi:10.1038/s41368-019-0064-z.
   Google Scholar
• Scapoli L, et al. Interleukin-6 gene polymorphism modulates the risk of periodontal diseases. J Biol Regul Homeost Agents Jul–Sep 2015;29(3 Suppl 1):111–116.
   Google Scholar
• Farhat SB, et al. Complete physical mapping of IL6 reveals a new marker associated with chronic periodontitis. J Periodontal Res 2017 Apr;52(2):255–261. doi:10.1111/jre.12389.
   Web of Science ®Google Scholar
• Trevilatto P, Scarel-Caminaga RM, de Brito RB Jr, de Souza AP, Line SR. Polymorphism at position -174 of IL-6 gene is associated with susceptibility to chronic periodontitis in a Caucasian Brazilian population. J Clin Periodontol 2003 May;30(5):438–442. doi:10.1034/j.1600-051x.2003.20016.x.
   Web of Science ®Google Scholar
• Toker H, Görgün EP, Korkmaz EM. Analysis of IL-6, IL-10 and NF- B gene polymorphisms in aggressive and chronic periodontitis. Cent Eur J Public Health 2017 Jun;25(2):157–162. doi:10.21101/cejph.a4656.
   PubMed Web of Science ®Google Scholar
• Pirim Gorgun E, Toker H, Korkmaz EM, Poyraz O. IL-6 and IL-10 gene polymorphisms in patients with aggressive periodontitis: Effects on GCF, serum and clinic parameters. Braz Oral Res 2017 Jan 16;31:e12. doi:10.1590/1807-3107BOR-2017.vol31.0012.
   Web of Science ®Google Scholar
• Nibali L, et al. Association between interleukin-6 promoter haplotypes and aggressive periodontitis. J Clin Periodontol 2008 Mar;35(3):193–198. doi:10.1111/j.1600-051X.2007.01188.x.
   Web of Science ®Google Scholar
• Shi D. Interleukin-6-572C/G polymorphism is associated with the risk of chronic periodontitis. Biomed Res 2017 Jun;28(15):6637–6639.
   Google Scholar
• Jingjin L, Zemin G, Xin M, et al. Correlation between an interleukin-6 -572C/G polymorphism and chronic periodontitis. Int J Periodontics Restorative Dent 2010 May–Jun;30(3):301–305.
   Google Scholar
• Holla LI, Fassmann A, Stejskalová A, Znojil V, Vaněk J, Vacha J. Analysis of the interleukin-6 gene promoter polymorphisms in Czech patients with chronic periodontitis. J Periodontol 2004 Jan;75(1):30–36. doi:10.1902/jop.2004.75.1.30.
   Web of Science ®Google Scholar
• Kavitha L, Vijayshree Priyadharshini J, Sivapathasundharam B. Association among interleukin-6 gene polymorphisms, Type 2 diabetes mellitus and chronic periodontitis: A pilot study. J Investig Clin Dent 2017 Aug;8(3). doi:10.1111/jicd.12230.
   Google Scholar
• Teixeira G, Mendonça SA, Menezes Oliveira K, et al. Interleukin-6 c.-174G>C polymorphism and periodontitis in a Brazilian population. Mol Biol Int 2014;2014:490308. doi: 10.1155/2014/490308.
   Google Scholar
• Tervonen T, Raunio T, Knuuttila M, Karttunen R. Polymorphisms in the CD14 and IL-6 genes associated with periodontal disease. J Clin Periodontol 2007 Apr;34(5):377–383. doi: 10.1111/j.1600-051X.2007.01067.x.
   Web of Science ®Google Scholar
• Babel N, Cherepnev G, Babel D, et al. Analysis of tumor necrosis factor-alpha, transforming growth factor-beta, interleukin-10, IL-6 and interferon-gamma gene polymorphisms in patients with chronic periodontitis. J Periodontol 2006 Dec;77(12):1978–1983. doi:10.1902/jop.2006.050315.
   Web of Science ®Google Scholar
• Brett P, Zygogianni P, Griffiths G, Tomaz M, Parkar M, Tonetti M. Functional gene polymorphisms in aggressive and chronic periodontitis. J Dent Res 2005 Dec;84(12):1149–1153. doi:10.1177/154405910508401211.
   Web of Science ®Google Scholar
• Zhu J, et al. Interleukin-6-174G/C polymorphism contributes to periodontitis susceptibility: An updated meta-analysis of 21 case-control studies. Dis Markers 2016;2016:9612421. doi: 10.1155/2016/9612421.
   Web of Science ®Google Scholar
• Zhang HY, Feng L, Wu H, Xie XD. The association of IL-6 and IL-6R gene polymorphisms with chronic periodontitis in a Chinese population. Oral Dis 2014 Jan;20(1):69–75. doi: 10.1111/odi.12075.
   Web of Science ®Google Scholar
• Sharma N, Joseph R, Arun R, Chandni R, Srinivas K, Banerjee M. Cytokine gene polymorphism (interleukin-1 +3954, interleukin-6 [-597/-174] and tumor necrosis factor- -308) in chronic periodontitis with and without Type 2 diabetes mellitus. Indian J Dent Res 2014 May–Jun25(3):375–380. doi:10.4103/0970-9290.138343.
   Google Scholar
• Komatsu Y, et al. Interleukin-6 (IL-6) — 373 A9T11 allele is associated with reduced susceptibility to chronic periodontitis in Japanese subjects and decreased serum IL-6 level. Tissue Antigens 2005 Jan;65(1):110–114. doi:10.1111/j.1399-0039.2005.00347.x.
   Google Scholar
• Raunio T, Nixdorf M, Knuuttila M, Karttunen R, Vainio O, Tervonen T. The extent of periodontal disease and the IL-6 -174 genotype as determinants of serum IL-6 level. J Clin Periodontol 2007 Oct;34(12):1025–1030. doi: 10.1111/j.1600-051X.2007.01151.x.
   Web of Science ®Google Scholar
• Dongari-Bagtzoglou AI, Ebersole JL. Production of inflammatory mediators and cytokines by human gingival fibroblasts following bacterial challenge. J Periodontal Res 1996 Feb;31(2):90–98. doi:10.1111/j.1600-0765.1996.tb00469.x.
   Web of Science ®Google Scholar
• Naruishi K, Nagata T. Biological effects of interleukin-6 on gingival fibroblasts: Cytokine regulation in periodontitis. J Cell Physiol 2018;233(9):6393–6400. doi:10.1002/jcp.26521.
   Google Scholar
• Bakker AD, Kulkarni RN, Klein-Nulend J, Lems WF. IL-6 alters osteocyte signaling toward osteoblasts but not osteoclasts. J Dent Res 2014 Apr;93(4):394–399. doi: 10.1177/0022034514522485.
   PubMed Web of Science ®Google Scholar
• Wu Q, Zhou X, Huang D, JI Y, Kang F. IL-6 Enhances osteocyte-mediated osteoclastogenesis by promoting JAK2 and RANKL activity. Cell Physiol Biochem 2017 May;41(4):1360–1369. doi: 10.1159/000465455.
   Google Scholar
• Irwin CR, Myrillas TT, Traynor P, Leadbetter N, Cawston TE. The role of soluble interleukin (IL)-6 receptor in mediating the effects of IL-6 on matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 expression by gingival fibroblasts. J Periodontol 2002 Jul;73(7):741–747. doi: 10.1902/jop.2002.73.7.741.
   Web of Science ®Google Scholar
• Cheng W, et al. Periodontitis associated pathogens P. gingivalis and A. actinomycetemcomitans activate human CD14 + monocytes leading to enhanced Th17/IL 17 responses. Eur J Immunol 2016 Sep;46(9):2211–2221. doi:10.1002/eji.201545871.
   PubMed Web of Science ®Google Scholar
• Nakamura T, Nitta H, Ishikawa I. Effect of low dose Actinobacillus actinomycetemcomitans lipopolysaccharide pretreatment on cytokine production by human whole blood. J Periodontal Res 2004 Apr;39(2):129–135. doi:10.1111/j.1600-0765.2004.00717.x.
   Web of Science ®Google Scholar
• Nagasawa T, Kobayashi H, Aramaki M, Kiji M, Oda S, Izumi Y. Expression of CD14, CD16 and CD45RA on monocytes from periodontitis patients. J Periodontal Res 2004 Feb;39(1):72–78. doi: 10.1111/j.1600-0765.2004.00713.x.
   Web of Science ®Google Scholar
• Stadler AF, Angst PDM, Arce RM, Gomes SC, Oppermann RV, Susin C. Gingival crevicular fluid levels of cytokines/chemokines in chronic periodontitis: A metaanalysis. J Clin Periodontol 2016 Sep;43(9):727–745. doi: 10.1111/jcpe.12557.
   Web of Science ®Google Scholar
• Reinhardt RA, et al. Gingival fluid IL-1 and IL-6 levels in refractory periodontitis. J Clin Periodontol 1993 Mar;20(3):225–231. doi: 10.1111/j.1600-051X.1993.tb00348.x.
   Web of Science ®Google Scholar
• Jaedicke KM, Preshaw PM, Taylor JJ. Salivary cytokines as biomarkers of periodontal diseases. Periodontol 2000 2016 Feb;70(1):164–183. doi: 10.1111/prd.12117.
   PubMed Web of Science ®Google Scholar
• Costa PP, et al. Salivary interleukin-6, matrix metalloproteinase-8 and osteoprotegerin in patients with periodontitis and diabetes. J Periodontol 2010 Mar;81(3):384–391. doi: 10.1902/jop.2009.090510.
   PubMed Web of Science ®Google Scholar
• Ebersole JL, et al. Patterns of salivary analytes provide diagnostic capacity for distinguishing chronic adult periodontitis from health. J Clin Immunol 2013 Jan;33(1):271–279. doi: 10.1007/s10875-012-9771-3.
   PubMed Web of Science ®Google Scholar
• Batool H, Nadeem A, Kashif M, Shahzad F, Tahir R, Afzal N. Salivary levels of IL-6 and IL-17 could be an indicator of disease severity in patients with calculus associated chronic periodontitis. Biomed Res Int 2018; 8531961. doi: 10.1155/2018/8531961.
   Web of Science ®Google Scholar
• Scannapieco FA, et al. Salivary biomarkers associated with alveolar bone loss. Ann N Y Acad Sci 2007;1098:496–497. doi: 10.1196/annals.1384.034.
   PubMed Web of Science ®Google Scholar
• Gursoy UK, et al. Salivary interleukin-1 concentration and the presence of multiple pathogens in periodontitis. J Clin Periodontol 2009 Nov;36(11):922–927. doi: 10.1111/j.1600-051X.2009.01480.x.
   PubMed Web of Science ®Google Scholar
• Bartold PM, Haynes DR. Interleukin-6 production by human gingival fibroblasts. J Periodontal Res 1991 Jul;26(4):339–345. doi: 10.1111/j.1600-0765.1991.tb02072.x.
   Web of Science ®Google Scholar
• Ross JH, Hardy DC, Schuyler CA, Slate EH, Mize TW, Huang Y. Expression of periodontal interleukin-6 protein is increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone and patients with both diseases. J Periodontal Res 2010 Oct;45(5):688–694. doi: 10.1111/j.1600-0765.2010.01286.x.
   Web of Science ®Google Scholar
• Noh MK, et al. Assessment of IL-6, IL-8 and TNF-levels in the gingival tissue of patients with periodontitis. Exp Ther Med 2013 Sep;6(3):847–851. doi: 10.3892/etm.2013.1222.
   PubMed Web of Science ®Google Scholar
• Marcaccini AM, et al. Circulating interleukin-6 and high-sensitivity c-reactive protein decrease after periodontal therapy in otherwise healthy subjects. J Periodontol 2009 Apr;80(4):594–602. doi: 10.1902/jop.2009.080561.
   Web of Science ®Google Scholar
• Sun XJ, et al. Elevation of C-reactive protein and interleukin-6 in plasma of patients with aggressive periodontitis. J Periodontal Res 2009 Jun;44(3):311–316. doi:10.1111/j.1600-0765.2008.01131.x.
   Web of Science ®Google Scholar
• Leira Y, et al. Periodontitis and systemic markers of neurodegeneration: A case-control study. J Clin Periodontol 2020 May;47(5). doi: 10.1111/jcpe.13267.
   Google Scholar
• Almaghlouth AA, et al. Effect of periodontal treatment on peak serum levels of inflammatory markers. Clin Oral Investig 2014 Dec;18(9):2113–2121. doi: 10.1007/s00784-014-1187-4.
   Web of Science ®Google Scholar
• D’Aiuto F, et al. Periodontitis and systemic inflammation: Control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res 2004 Feb;83(2):156–160. doi: 10.1177/154405910408300214.
   PubMed Web of Science ®Google Scholar
• de Moura Leite SA, et al. The effect of nonsurgical periodontal therapy on hepcidin and on inflammatory and iron marker levels. Braz Oral Res 2019 Sep;33:e055. doi: 10.1590/1807-3107bor-2019.vol33.0055.
   Google Scholar
• Shimada Y, Komatsu Y, Ikezawa-Suzuki I, Tai H, Sugita N, Yoshie H. The effect of periodontal treatment on serum leptin, interleukin-6 and C-reactive protein. J Periodontol 2010 Aug;81(8):1118–1123. doi: 10.1902/jop.2010.090741.
   Web of Science ®Google Scholar
• Lobâo WJM, et al. Relationship between periodontal outcomes and serum biomarkers changes after nonsurgical periodontal therapy. An Acad Bras Cienc 2019 May;91(2):e20170652. doi: 10.1590/00013765201920170652.
   Web of Science ®Google Scholar
• D’Aiuto F, Parkar M, Nibali L, Suvan J, Lessem J, Tonetti MS. Periodontal infections cause changes in traditional and novel cardiovascular risk factors: Results from a randomized controlled clinical trial. Am Heart J 2006 May;151(5):977–984. doi: 10.1016/j.ahj.2005.06.018.
   PubMed Web of Science ®Google Scholar
• Lima R, et al. Effect of periodontal therapy on serum levels of IL-6 in Type 2 diabetics: A systematic review. Int J Periodontics Restorative Dent 2019 Jan-Feb;39(1):e1–e10. doi: 10.11607/prd.3866.
   Google Scholar
• Montenegro MM, et al. Randomized controlled trial of the effect of periodontal treatment on cardiovascular risk biomarkers in patients with stable coronary artery disease: Preliminary findings of 3 months. J Clin Periodontol 2019 Mar;46(3):321–331. doi: 10.1111/jcpe.13085.
   PubMed Web of Science ®Google Scholar
• Torumtay G, Kirzioğlu FY, Öztürk Tonguç M, Kale B, Calapoğlu M, Orhan H. Effects of periodontal treatment on inflammation and oxidative stress markers in patients with metabolic syndrome. J Periodontal Res 2016 Aug;51(4):489–498. doi: 10.1111/jre.12328.
   PubMed Web of Science ®Google Scholar
• Vos T, et al. Global, regional, and national incidence, prevalence and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017 Sep 16;390(10100):1211–1259. doi: 10.1016/S0140-6736(17)32154-2.
   PubMed Web of Science ®Google Scholar
• Zeng XT, Tu ML, Liu DY, Zheng D, Zhang J, Leng WD. Periodontal disease and risk of chronic obstructive pulmonary disease: A meta-analysis of observational studies. PLoS One 2012;7(10). doi: 10.1371/journal.pone.0046508.
   Google Scholar
• Shen TC, et al. Risk of periodontal diseases in patients with chronic obstructive pulmonary disease a nationwide population-based cohort study. Medicine (Baltimore) 2015 Nov;94(46):e2047. doi: 10.1097/MD.0000000000002047.
   Web of Science ®Google Scholar
• Öztekin G, et al. The association between periodontal disease and chronic obstructive pulmonary disease: A case control study. COPD 2014 Aug;11(4):424–430. doi: 10.3109/15412555.2013.858316.
   PubMedGoogle Scholar
• Raghavendran K, Mylotte JM, Scannapieco FA. Nursing home-associated pneumonia, hospital-acquired pneumonia and ventilator-associated pneumonia: The contribution of dental biofilms and periodontal inflammation. Periodontol 2000 2007;44(1):164–177. doi: 10.1111/j.1600-0757.2006.00206.x.
   Google Scholar
• Scannapieco FA, Bush RB, Paju S. Associations between periodontal disease and risk for nosocomial bacterial pneumonia and chronic obstructive pulmonary disease. A systematic review. Ann Periodontol 2003 Dec;8:54–69. doi: 10.1902/annals.2003.8.1.54.
   PubMedGoogle Scholar
• Azarpazhooh A, Leake JL. Systematic review of the association between respiratory diseases and oral health. J Periodontol 2006 Sep;77(9):1465–1482. doi: 10.1902/jop.2006.060010.
   PubMed Web of Science ®Google Scholar
• Sabharwal A, Gomes-Filho IS, Stellrecht E, Scannapieco FA. Role of periodontal therapy in management of common complex systemic diseases and conditions: An update. Periodontol 2000 2018 Oct;78(1):212–226. doi: 10.1111/prd.12226.
   Web of Science ®Google Scholar
• Ćabov T, et al. The impact of oral health and 0.2% chlorhexidine oral gel on the prevalence of nosocomial infections in surgical intensive-care patients: A randomized placebo-controlled study. Wien Klin Wochenschr 2010 Jul;122(13-14):397–404. doi:10.1007/s00508-010-1397-y.
   Web of Science ®Google Scholar
• Akutsu Y, et al. Pre-operative dental brushing can reduce the risk of postoperative pneumonia in esophageal cancer patients. Surgery 2010 Apr;147(4):497–502. doi: 10.1016/j.surg.2009.10.048.
   Web of Science ®Google Scholar
• Hollaar VRY, Van Der Putten GJ, Van Der Maarel-Wierink CD, Bronkhorst EM, De Swart BJM, Creugers NHJ. The effect of a daily application of a 0.05% chlorhexidine oral rinse solution on the incidence of aspiration pneumonia in nursing home residents: A multicenter study. BMC Geriatr 2017 Jun;17(1):128. doi: 10.1186/s12877-017-0519-z.
   PubMedGoogle Scholar
• Bellissimo-Rodrigues WT, et al. Effectiveness of a dental care intervention in the prevention of lower respiratory tract nosocomial infections among intensive care patients: A randomized clinical trial. Infect Control Hosp Epidemiol 2014 Nov;35(11):1342–1348. doi: 10.1086/678427.
   Web of Science ®Google Scholar
• Peter KP, Mute BR, Doiphode SS, Bardapurkar SJ, Borkar MS, Raje DV. Association between periodontal disease and chronic obstructive pulmonary disease: A reality or just a dogma? J Periodontol 2013 Dec;84(12):1717–1723. doi: 10.1902/jop.2013.120347.
   Web of Science ®Google Scholar
• Holtfreter B, Richter S, Kocher T, et al. Periodontitis is related to lung volumes and airflow limitation: A crosssectional study. Eur Respir J 2013 Dec;42(6):1524–1535. doi: 10.1183/09031936.00109112.
   Web of Science ®Google Scholar
• Lee W, et al. Association between periodontitis and pulmonary function based on the Third National Health and Nutrition Examination Survey (NHANES III). J Clin Periodontol 2020 Jul;47(7);788-795. doi: 10.1111/jcpe.13303.
   Google Scholar
• Zhou X, Han J, Liu Z, Song Y, Wang Z, Sun Z. Effects of periodontal treatment on lung function and exacerbation frequency in patients with chronic obstructive pulmonary disease and chronic periodontitis: A 2-year pilot randomized controlled trial. J Clin Periodontol 2014 Jun;41(6):564–572. doi: 10.1111/jcpe.12247.
   PubMed Web of Science ®Google Scholar
• Lee E, Lee SW. Prevalence of periodontitis and its association with reduced pulmonary function: Results from the Korean national health and nutrition examination survey. Medicine (Kaunas) 2019 Sep;55(9):581. doi: 10.3390/medicina55090581.
   Web of Science ®Google Scholar
• Moraschini V, de Albuquerque Calasans-Maia J, Diuana Calasans-Maia M. Association between asthma and periodontal disease: A systematic review and metaanalysis. J Periodontol 2017;89(4):1–20. doi: 10.1902/jop.2017.170363.
   Google Scholar
• Ferreira MKM, et al. Is there an association between asthma and periodontal disease among adults? Systematic review and meta-analysis. Life Sci 2019 Apr;223:74–87. doi: 10.1016/j.lfs.2019.03.005.
   PubMed Web of Science ®Google Scholar
• Soledade-Marques KR, et al. Association between periodontitis and severe asthma in adults: A case-control study. Oral Dis 2017:1–7. doi:10.1111/odi.12737.
   Google Scholar
• Spinelli A, Pellino G. COVID-19 pandemic: Perspectives on an unfolding crisis. Br J Surg 2020;107(7):785–787. doi: 10.1002/bjs.11627.
   Google Scholar
• Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med 2020;8(5):475–481. doi: 10.1016/S2213-2600(20)30079-5.
   Google Scholar
• Xu J, Li Y, Gan F, Du Y, Yao Y. Salivary glands: Potential reservoirs for COVID-19 asymptomatic infection. J Dent Res 2020 99(8):989. doi: 10.1177/0022034520918518.
   Google Scholar
• Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med 2020 Apr;18(1):164. doi: 10.1186/s12967-020-02339-3.
   PubMed Web of Science ®Google Scholar
• Borges ÁH, O’Connor JL, Phillips AN, et al. Factors associated with plasma IL-6 levels during HIV infection. J Infect Dis 2015;212(4):585–595. doi: 10.1093/infdis/jiv123.
   Google Scholar
• Dienz O, Rincon M. The effects of IL-6 on CD4 T cell responses. Clin Immunol 2009;130(1):27–33. doi: 10.1016/j.clim.2008.08.018.
   Google Scholar
• Lan T, Chang L, Wu L, Yuan Y-F. IL-6 plays a crucial role in HBV infection. J Clin Transl Hepatol 2015;3(4):271–276. doi: 10.14218/JCTH.2015.00024.
   Google Scholar
• Coomes EA, Haghbayan H. Interleukin-6 in COVID-19: A systematic review and meta-analysis. MedRxiv 2020:20048058. doi:10.1101/2020.03.30.20048058.
   Google Scholar
• Xu X, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A 2020;117(20):10970–10975. doi: 10.1073/pnas.2005615117.
   Google Scholar
• Ledford H. Coronavirus breakthrough: Dexamethasone is first drug shown to save lives. Nature 2020;582(7813):469. doi: 10.1038/d41586-020-01824-5.
   Google Scholar
• Armitage LC, Brettell R. Inhaled corticosteroids: A rapid review of the evidence for treatment or prevention of COVID-19. Cent Evidence-Based Med Univ Oxford 2020.
   Google Scholar
• Dias IHK, Matthews JB, Chapple ILC, Wright HJ, Dunston CR, Griffiths HR. Activation of the neutrophil respiratory burst by plasma from periodontitis patients is mediated by proinflammatory cytokines. J Clin Periodontol 2011;38(1):1–7. doi: 10.1111/j.1600-051X.2010.01628.x.
   Google Scholar
• Thoden van Velzen SK, Abraham Inpijn L, Moorer WR. Plaque and systemic disease: A reappraisal of the focal infection concept. J Clin Periodontol 1984;11(4):209–220. doi: 10.1111/j.1600-051X.1984.tb02211.x.
   Google Scholar
• Scannapieco FA. Role of oral bacteria in respiratory infection. J Periodontol 1999;70(7):793–802. doi: 10.1902/jop.1999.70.7.793.
   Google Scholar
• Munro CL, Grap MJ, Elswick RK, McKinney J, Sessler CN, Hummel RS. Oral health status and development of ventilator-associated pneumonia: A descriptive study. Am J Crit Care 2006;15(5):453–460. doi: 10.4037/ajcc2006.15.5.453.
   Google Scholar
• Chen AC, Liu CC, Yao WJ, Chen CT, Wang JY. Actinobacillus actinomycetemcomitans pneumonia with chest wall and subphrenic abscess. Scand J Infect Dis 1995;27(3):289–290. doi: 10.3109/00365549509019023.
   Google Scholar
• Scannapieco FA, Wang B, Shiau HJ. Oral bacteria and respiratory infection: Effects on respiratory pathogen adhesion and epithelial cell proinflammatory cytokine production. Ann Periodontol 2001;6(1):78–86. doi: 10.1902/annals.2001.6.1.78.
   Google Scholar
• Budden KF, et al. Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol 2017;15(1):55–63. doi: 10.1038/nrmicro.2016.142.
   Google Scholar
• Hajishengallis G. Periodontitis: From microbial immune subversion to systemic inflammation. Nat Rev Immunol 2015;15(1):30—44. doi: 10.1038/nri3785.
   Google Scholar
• Walker MY, Pratap S, Southerland JH, Farmer-Dixon CM, Lakshmyya K, Gangula PR. Role of oral and gut microbiome in nitric oxide-mediated colon motility. Nitric Oxide 2018;73:81–88. doi: 10.1016/j.niox.2017.06.003.
   PubMed Web of Science ®Google Scholar
• Seedorf H, Griffin NW, Ridaura VK, et al. Bacteria from diverse habitats colonize and compete in the mouse gut. Cell 2014;159(2):253–266. doi: 10.1016/j.cell.2014.09.008.
   Google Scholar
• Moura MF, et al. Periodontitis and endothelial dysfunction: Periodontal clinical parameters and levels of salivary markers interleukin-1, tumor necrosis factor-, matrix metalloproteinase-2, tissue inhibitor of metalloproteinases-2 complex and nitric oxide. J Periodontol 2017;88(8):778–787. doi: 10.1902/jop.2017.170023.
   Google Scholar
• Orlandi M, et al. Association between periodontal disease and its treatment, flow-mediated dilatation and carotid intima-media thickness: A systematic review and meta-analysis. Atherosclerosis 2014;236(1). doi: 10.1016/j.atherosclerosis.2014.06.002.
   Google Scholar
• Higashi Y, et al. Periodontal infection is associated with endothelial dysfunction in healthy subjects and hypertensive patients. Hypertension 2008;51:446–453. doi: 10.1161/HYPERTENSIONAHA.107.101535.
   PubMed Web of Science ®Google Scholar
• Rohleder N, Aringer M, Boentert M. Role of interleukin-6 in stress, sleep and fatigue. Ann N Y Acad Sci 2012;1261(1):88–96. doi: 10.1111/j.1749-6632.2012.06634.x.
   Google Scholar
• Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323(13):1239–1242. doi: 10.1001/jama.2020.2648.
   Google Scholar
• Yang LC, Suen YJ, Wang YH, Lin TC, Yu HC, Chang YC. The association of periodontal treatment and decreased pneumonia: A nationwide population-based cohort study. Int J Environ Res Public Health 2020;17(1). doi: 10.3390/ijerph17010356.
   Google Scholar
• Santaella N, Santos P, De Souza IS, Santaella NG, Sérgio P, Santos S. The practice of hospital dentistry in Brazil: An integrative literature review. Rev Bras Odontol 2017;74(3):232–241. doi: 10.18363/rbo.v74n3.p.232.
   Google Scholar
• O’Donnell VB, et al. Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection. Function 2020;1(1). doi: 10.1093/function/zqaa002.
   Google Scholar
• Challacombe SJ, Kirk-Bayley J, Sunkaraneni VS, Combes J. Povidone iodine. Br Dent J 2020;228(9):656–657. doi: 10.1038/s41415-020-1589-4.
   Google Scholar
• Kotsakis GA, Lian Q, Ioannou AL, Michalowicz BS, John MT, Chu H. A network meta-analysis of interproximal oral hygiene methods in the reduction of clinical indices of inflammation. J Periodontol 2018;89(5):558–570. doi: 10.1002/JPER.17-0368.
   Google Scholar
• Chapple ILC, Van Der Weijden F, Doerfer C, et al. Primary prevention of periodontitis: Managing gingivitis. J Clin Periodontol 2015;42(S16):S71–S76. doi:10.1111/jcpe.12366.
   Google Scholar
• CDC. Center for Disease Control. www.cdc.gov/coronavirus/2019-ncov/cases-updates/hospitalizations-forecasts.html. Published 2020.
   Google Scholar
• Carvajal P, Gómez M, Gomes S, et al. Prevalence, severity, and risk indicators of gingival inflammation in a multi-center study on South American adults: A cross sectional study. J Appl Oral Sci 2016;24(5):524. doi: 10.1590/1678–775720160178.
   Google Scholar