Consilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum11244710.26442/20751753.2022.5.201755Review ArticleChanges in the organs and tissues of the oral cavity in the new coronavirus infection (COVID-19): A reviewTrukhanDmitry I.<p>D. Sci. (Med.), Assoc. Prof., Omsk State Medical University</p>dmitry_trukhan@mail.ruhttps://orcid.org/0000-0002-1597-1876SulimovAnatoly F.<p>D. Sci. (Med.), Prof., Omsk State Medical University</p>afsulimov@yandex.ruTrukhanLarissa Yu.<p>Cand. Sci. (Med.), Omsk State Medical University</p>larissa_trukhan@mail.ruhttps://orcid.org/0000-0002-4721-6605Omsk State Medical University150520222453493570811202208112022Copyright © 2022, Consilium Medicum2022<p>SARS-CoV-2 infection can cause changes in the organs and tissues of the oral cavity, which is associated with a wide distribution of angiotensin-converting enzyme type 2 in the oral cavity, mainly epithelial cells of the oral mucosa, gums and fibroblasts of the periodontal ligament. Thus, the oral mucosa is susceptible to SARS-CoV-2 infection and may act as a gateway for the virus, as well as a reservoir for SARS-CoV-2. We searched the literature for the period from the beginning of the pandemic until May 30, 2022, devoted to the study of changes in the organs and tissues of the oral cavity with a new coronavirus infection (COVID-19) in the electronic search engines PubMed/MEDLINE and Scopus. A special place in the study of changes in the organs and tissues of the oral cavity with a new coronavirus infection (COVID-19) is occupied by periodontal pathology. A number of reviews and clinical studies conclude the importance of good oral hygiene and periodontal health as an important aspect of COVID-19 prevention and management. Oral probiotics can be considered as a promising direction for correcting changes in organs and tissues of the oral cavity in COVID-19.</p>oral cavitynovel coronavirus infectionCOVID-19periodontal pathologyperiodontitisclinical associationoral probioticsStreptococcus salivariusполость ртановая коронавирусная инфекцияCOVID-19патология пародонтапародонтитклиническая ассоциацияоральные пробиотикиStreptococcus salivarius[Временные методические рекомендации Минздрава РФ «Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19)» (15-я версия от 22.02.2022). Режим доступа: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/059/392/original/%D0%92%D0%9C%D0%A0_COVID-19_V15.pdf. Ссылка активна на 26.05.2022 [Vremennye metodicheskie rekomendatsii Minzdrava RF "Profilaktika, diagnostika i lechenie novoi koronavirusnoi infektsii (COVID-19)" (15-ia versiia ot 22.02.2022). Available: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/059/392/original/%D0%92%D0%9C%D0%A0_COVID-19_V15.pdf. Accessed: 26.05.2022 (in Russian)].][Casillas Santana MA, Arreguín Cano JA, Dib Kanán A, et al. Should We Be Concerned about the Association of Diabetes Mellitus and Periodontal Disease in the Risk of Infection by SARS-CoV-2? A Systematic Review and Hypothesis. Medicina (Kaunas). 2021;57(5):493. DOI:10.3390/medicina57050493][Silvestre FJ, Márquez-Arrico CF. COVID-19 and Periodontitis: A Dangerous Association? Front Pharmacol. 2022;12:789681. DOI:10.3389/fphar.2021.789681][Jafer MA, Hazazi MA, Mashi MH, et al. COVID-19 and Periodontitis: A Reality to Live with. J Contemp Dent Pract. 2020;21(12):1398-403.][Campisi G, Bizzoca ME, Lo Muzio L. COVID-19 and periodontitis: reflecting on a possible association. Head Face Med. 2021;17(1):16. DOI:10.1186/s13005-021-00267-1][Kusiak A, Cichońska D, Tubaja M, et al. COVID-19 manifestation in the oral cavity – a narrative literature review. Acta Otorhinolaryngol Ital. 2021;41(5):395-400. DOI:10.14639/0392-100X-N1584][Basso L, Chacun D, Sy K, et al. Periodontal Diseases and COVID-19: A Scoping Review. Eur J Dent. 2021;15(4):768-75. DOI:10.1055/s-0041-1729139][Grigoriadis A, Räisänen IT, Pärnänen P, et al. Is There a Link between COVID-19 and Periodontal Disease? A Narrative Review. Eur J Dent. 2022;16(3):514-20. DOI:10.1055/s-0041-1740223][Brock M, Bahammam S, Sima C. The Relationships Among Periodontitis, Pneumonia and COVID-19. Front Oral Health. 2022;2:801815. DOI:10.3389/froh.2021.801815][Salas Orozco MF, Niño-Martínez N, Martínez-Castañón GA, et al. Presence of SARS-CoV-2 and Its Entry Factors in Oral Tissues and Cells: A Systematic Review. Medicina (Kaunas). 2021;57(6):523. DOI:10.3390/medicina57060523][Gupta S, Mohindra R, Chauhan PK, et al. SARS-CoV-2 detection in gingival crevicular fluid. J Dent Res. 2021;100(2):187-93. DOI:10.1177/0022034520970536][Sahni V. SARS CoV-2 load in periodontal disease. J Am Dent Assoc. 2022;153(1):14. DOI:10.1016/j.adaj.2021.10.010][Berton F, Rupel K, Florian F, et al. Dental calculus: a reservoir for detection of past SARS-CoV-2 infection. Clin Oral Investig. 2021;25(8):5113-4. DOI:10.1007/s00784-021-04001-8][Gomes SC, Fachin S, da Fonseca JG, et al. Dental biofilm of symptomatic COVID-19 patients harbours SARS-CoV-2. J Clin Periodontol. 2021;48(7):880-5. DOI:10.1111/jcpe.13471][Gupta S, Mohindra R, Singla M, et al. The clinical association between Periodontitis and COVID-19. Clin Oral Investig. 2022;26(2):1361-74. DOI:10.1007/s00784-021-04111-3][Brandini DA, Takamiya AS, Thakkar P, et al. Covid-19 and oral diseases: Crosstalk, synergy or association? Rev Med Virol. 2021;31(6):e2226. DOI:10.1002/rmv.2226][Iranmanesh B, Khalili M, Amiri R, et al. Oral manifestations of COVID-19 disease: A review article. Dermatol Ther. 2021;34(1):e14578. DOI:10.1111/dth.14578][Daly J, Black EAM. The impact of COVID-19 on population oral health. Community Dent Health. 2020;37(4):236-8. DOI:10.1922/CDH_Dec20editorialDalyBlack03][Martín Carreras-Presas C, Amaro Sánchez J, López-Sánchez AF, et al. Oral vesiculobullous lesions associated with SARS-CoV-2 infection. Oral Dis. 2021;27(Suppl. 3):710-2. DOI:10.1111/odi.13382][Cuevas-Gonzalez MV, Espinosa-Cristóbal LF, Donohue-Cornejo A, et al. COVID-19 and its manifestations in the oral cavity: A systematic review. Medicine (Baltimore). 2021;100(51):e28327. DOI:10.1097/MD.0000000000028327][Farid H, Khan M, Jamal S, Ghafoor R. Oral manifestations of Covid-19-A literature review. Rev Med Virol. 2022;32(1):e2248. DOI:10.1002/rmv.2248][Eghbali Zarch R, Hosseinzadeh P. COVID-19 from the perspective of dentists: A case report and brief review of more than 170 cases. Dermatol Ther. 2021;34(1):e14717. DOI:10.1111/dth.14717][Surboyo MD, Ernawati DS, Budi HS. Oral mucosal lesions and oral symptoms of the SARS-CoV-2 infection. Minerva Dent Oral Sci. 2021;70(4):161-8. DOI:10.23736/S2724-6329.21.04493-9][Amorim Dos Santos J, Normando AGC, Carvalho da Silva RL, et al. Oral Manifestations in Patients with COVID-19: A 6-Month Update. J Dent Res. 2021;100(2):141-54. DOI:10.1177/0022034520957289][Doceda MV, Gavriiloglou M, Petit C, Huck O. Oral Health Implications of SARS-CoV-2/COVID-19: A Systematic Review. Oral Health Prev Dent. 2022;20(1):207-18. DOI:10.3290/j.ohpd.b2960801][Fakhruddin KS, Samaranayake LP, Buranawat B, Ngo H. Oro-facial mucocutaneous manifestations of Coronavirus Disease-2019 (COVID-19): A systematic review. PLoS One. 2022;17(6):e0265531. DOI:10.1371/journal.pone.0265531][Santana LADM, Vieira WA, Gonçalo RIC, et al. Oral mucosa lesions in confirmed and non-vaccinated cases for COVID-19: A systematic review. J Stomatol Oral Maxillofac Surg. 2022;123(5):e241-50. DOI:10.1016/j.jormas.2022.05.005][Sirin DA, Ozcelik F. The relationship between COVID-19 and the dental damage stage determined by radiological examination. Oral Radiol. 2021;37(4):600-9. DOI:10.1007/s11282-020-00497-0][Qi X, Northridge ME, Hu M, Wu B. Oral health conditions and COVID-19: A systematic review and meta-analysis of the current evidence. Aging Health Res. 2022;2(1):100064. DOI:10.1016/j.ahr.2022.100064][Трухан Д.И., Трухан Л.Ю. Пародонтит и сердечно-сосудистые заболевания: параллельно или в одной связке? Consilium Medicum. 2015;17(5):73-9. Режим доступа: https://elibrary.ru/item.asp?id=23762074. Ссылка активна на 26.05.2022 [Trukhan DI, Trukhan LYu. Periodontal and cardiovascular diseases: in parallel or in a bundle? Consilium Medicum. 2015;17(5):73-9. Available: https://elibrary.ru/item.asp?id=23762074. Accessed: 26.05.2022 (in Russian)].][Гришечкина И.А., Трухан Л.Ю., Трухан Д.И., Коншу Н.В. Оценка состояния гигиены полости рта и тканей пародонта у больных сахарным диабетом II типа. Dental Forum. 2014;3:45-50. Режим доступа: https://elibrary.ru/item.asp?id=21615957. Ссылка активна на 26.05.2022 [Grishechkina IA, Trukhan DI, Trukhan LYu, Konshu NV. Evaluation of oral hygiene and periodontal status in patients with type ii diabetes. Dental Forum. 2014;3:45-50. Available: https://elibrary.ru/item.asp?id=21615957. Accessed: 26.05.2022 (in Russian)].][Bascones-Martínez A, Muñoz-Corcuera M, Bascones-Ilundain J. Diabetes and periodontitis: A bidirectional relationship. Med Clin (Barc). 2015;145(1):31-5. DOI:10.1016/j.medcli.2014.07.019][Трухан Д.И., Трухан Л.Ю. Некоторые аспекты коморбидности пародонтита и сердечно-сосудистых заболеваний. Медицинский совет. 2015;17:12-6. Режим доступа: https://www.med-sovet.pro/jour/article/view/419. Ссылка активна на 26.05.2022 [Trukhan DI, Trukhan LYu. Some aspects of periodontal disease and comorbid cardiovascular diseases. Medical advice. 2015;17:12-6. Available: https://www.med-sovet.pro/jour/article/view/419. Accessed: 26.05.2022 (in Russian)].][Трухан Л.Ю., Трухан Д.И. Стоматологические проблемы гастроэнтерологических пациентов и возможные пути их решения. Медицинский совет. 2016;19:134-7. Режим доступа: https://www.med-sovet.pro/jour/article/view/1641. Ссылка активна на 26.05.2022 [Trukhan DI, Trukhan LYu. Stomatoligical problems of gastroenterological patients and their possible solutions. Medical advice. 2016;19:134-7. Available: https://www.med-sovet.pro/jour/article/view/1641. Accessed: 26.05.2022 (in Russian)].][Трухан Д.И., Трухан Л.Ю. Взаимоотношения болезней пародонта и сердечно-сосудистых заболеваний. Международный журнал сердца и сосудистых заболеваний. 2016;4(11):15-24. Режим доступа: http://heart-vdj.com/files/2016,%2011/t4n11_4.pdf. Ссылка активна на 26.05.2022 [Trukhan DI, Trukhan LYu. Relationship between periodontal and cardiovascular diseases. International Journal of Heart and Vascular Diseases. 2016;4(11):15-24. Available: http://heart-vdj.com/files/2016,%2011/t4n11_4.pdf. Accessed: 26.05.2022 (in Russian)].][Borgnakke WS. IDF Diabetes Atlas: Diabetes and oral health – A two-way relationship of clinical importance. Diabetes Res Clin Pract. 2019;157:107839. DOI:10.1016/j.diabres.2019.107839.][Трухан Д.И., Трухан Л.Ю., Иванова Д.С. Коморбидность заболеваний сердечно-сосудистой системы и болезней органов пищеварения с изменениями органов и тканей полости рта. Клинический разбор в общей медицине. 2021;3:6-17 [Trukhan DI, Trukhan LYu, Ivanova DS. Comorbidity of diseases of the cardiovascular system and diseases of the digestive organs with changes in organs and tissue of the oral cavity. Clinical review for general practice. 2021;3:6-17 (in Russian)]. DOI:10.47407/kr2021.2.3.00044][Трухан Д.И., Иванова Д.С., Трухан Л.Ю. Гастроэнтерологические проблемы пациентов с сахарным диабетом. Focus Эндокринология. 2021;3:52-61 [Trukhan DI, Ivanova DS, Trukhan LYu. Gastroenterological problems of patients with diabetes mellitus. Focus Endokrinologiia. 2021;3:52-61 (in Russian)]. DOI:10.47407/ef2021.2.3.0035][Гриневич В.Б., Губонина И.В., Дощицин В.Л., и др. Особенности ведения коморбидных пациентов в период пандемии новой коронавирусной инфекции (COVID-19). Национальный Консенсус 2020. Кардиоваскулярная терапия и профилактика. 2020;19(4):2630 [Grinevich VB, Gubonina IV, Doshchitsin VL, et. al. Management of patients with comorbidity during novel coronavirus (COVID-19) pandemic. National Consensus Statement 2020. Cardiovascular Therapy and Prevention. 2020;19(4):2630 (in Russian)]. DOI:10.15829/1728-88002020-2630][Ghosh A, Joseph B, Anil S. Does periodontitis influence the risk of COVID-19? A scoping review. Clin Exp Dent Res. 2022. DOI:10.1002/cre2.584][Sahni V, Gupta S. COVID-19 & Periodontitis: The cytokine connection. Med Hypotheses. 2020;144:109908. DOI:10.1016/j.mehy.2020.109908][Marouf N, Cai W, Said KN, et al. Association between Periodontitis and Severity of COVID-19 Infection: A Case-Control Study. J Clin Periodontol. 2021;48(4):483-91. DOI:10.1111/jcpe.13435][Sukumar K, Tadepalli A. Nexus between COVID-19 and periodontal disease. J Int Med Res. 2021;49(3):3000605211002695. DOI:10.1177/03000605211002695][Bao L, Zhang C, Dong J, et al. Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection. Front Microbiol. 2020;11:1840. DOI:10.3389/fmicb.2020.01840][Aquino-Martinez R, Hernández-Vigueras S. Severe COVID-19 Lung Infection in Older People and Periodontitis. J Clin Med. 2021;10(2):279. DOI:10.3390/jcm10020279][Imai K, Iinuma T, Sato S. Relationship between the oral cavity and respiratory diseases: Aspiration of oral bacteria possibly contributes to the progression of lower airway inflammation. Jpn Dent Sci Rev. 2021;57:224-30. DOI:10.1016/j.jdsr.2021.10.003][Magán-Fernández A, O'Valle F, Abadía-Molina F, et al. Characterization and Comparison of Neutrophil Extracellular Traps in Gingival Samples of Periodontitis and Gingivitis: A Pilot Study. J Periodontal Res. 2019;54(3):218-24. DOI:10.1111/jre.12621][Borges L, Pithon-Curi TC, Curi R, Hatanaka E. COVID-19 and neutrophils: the relationship between hyperinflammation and neutrophil extracellular traps. Mediators Inflamm. 2020;2020:8829674. DOI:10.1155/2020/8829674][Gupta S, Sahni V. The intriguing commonality of NETosis between COVID-19 & Periodontal disease. Med Hypotheses. 2020;144:109968. DOI:10.1016/j.mehy.2020.109968][Magán-Fernández A, Rasheed Al-Bakri SM, O'Valle F, et al. Neutrophil Extracellular Traps in Periodontitis. Cells. 2020;9(6):1494. DOI:10.3390/cells9061494][Larvin H, Wilmott S, Wu J, Kang J. The impact of periodontal disease on hospital admission and mortality during COVID-19 pandemic. Front Med (Lausanne). 2020;7:604980. DOI:10.3389/fmed.2020.604980][Boyapati R, Dhulipalla R, Kolaparthy LK, Bodduru R. COVID-19 and oral implications: An updated review. J Oral Maxillofac Pathol. 2021;25(3):400-3. DOI:10.4103/jomfp.jomfp_198_21][Larvin H, Wilmott S, Kang J, et al. Additive Effect of Periodontal Disease and Obesity on COVID-19 Outcomes. J Dent Res. 2021;100(11):1228-35. DOI:10.1177/00220345211029638][Costa CA, Vilela ACS, Oliveira SA, et al. Poor oral health status and adverse COVID-19 outcomes: a preliminary study in hospitalized patients. J Periodontol. 2022:10.1002/JPER.21-0624. DOI:10.1002/JPER.21-0624][Anand PS, Jadhav P, Kamath KP, et al. A case-control study on the association between periodontitis and coronavirus disease (COVID-19). J Periodontol. 2022;93(4):584-90. DOI:10.1002/JPER.21-0272][Botros N, Iyer P, Ojcius DM. Is there an association between oral health and severity of COVID-19 complications? Biomed J. 2020;43(4):325-7. DOI:10.1016/j.bj.2020.05.016][Kouanda B, Sattar Z, Geraghty P. Periodontal Diseases: Major Exacerbators of Pulmonary Diseases? Pulm Med. 2021;2021:4712406. DOI:10.1155/2021/4712406][Wang Y, Deng H, Pan Y, et al. Periodontal disease increases the host susceptibility to COVID-19 and its severity: a Mendelian randomization study. J Transl Med. 2021;19(1):528. DOI:10.1186/s12967-021-03198-2][Трухан Д.И. Нарушения кишечного микробиоценоза: расширение сферы применения пробиотиков. Медицинский совет. 2022;16(7):132-43 [Trukhan DI. Disorders of intestinal microbiocenosis: expanding the application of probiotics. Meditsinskiy sovet. 2022;16(7):132-43 (in Russian)]. DOI:10.21518/2079-701X-2022-16-7-132-143][Khan AA, Singh H, Bilal M, Ashraf MT. Microbiota, probiotics and respiratory infections: the three musketeers can tip off potential management of COVID-19. Am J Transl Res. 2021;13(10):10977-93.][Di Pierro F. A possible probiotic (S. salivarius K12) approach to improve oral and lung microbiotas and raise defenses against SAR S-CoV-2. Minerva Med. 2020;111(3):281-3. DOI:10.23736/S0026-4806.20.06570-2][Di Pierro F, Colombo M. The administration of S. salivarius K12 to children may reduce the rate of SARS-CoV-2 infection. Minerva Med. 2021;112(4):514-6. DOI:10.23736/S0026-4806.21.07487-5][Wescombe PA, Hale JD, Heng NC, Tagg JR. Developing oral probiotics from Streptococcus salivarius. Future Microbiol. 2012;7(12):1355-71. DOI:10.2217/fmb.12.113][Horz HP, Meinelt A, Houben B, Conrads G. Distribution and persistence of probiotic Streptococcus salivarius K12 in the human oral cavity as determined by real-time quantitative polymerase chain reaction. Oral Microbiol Immunol. 2007;22(2):126-30. DOI:10.1111/j.1399-302X.2007.00334.x][Di Pierro F, Adami T, Rapacioli G, et al. Clinical evaluation of the oral probiotic Streptococcus salivarius K12 in the prevention of recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes in adults. Expert Opin Biol Ther. 2013;13(3):339-43. DOI:10.1517/14712598.2013.758711][Cosseau C, Devine DA, Dullaghan E, et al. The commensal Streptococcus salivarius K12 downregulates the innate immune responses of human epithelial cells and promotes host-microbe homeostasis. Infect Immun. 2008;76(9):4163-75. DOI:10.1128/IAI.00188-08][Laws GL, Hale JDF, Kemp RA. Human Systemic Immune Response to Ingestion of the Oral Probiotic Streptococcus salivarius BLIS K12. Probiotics Antimicrob Proteins. 2021;13(6):1521-9. DOI:10.1007/s12602-021-09822-3][Burton JP, Chilcott CN, Wescombe PA, Tagg JR. Extended Safety Data for the Oral Cavity Probiotic Streptococcus salivarius K12. Probiotics Antimicrob Proteins. 2010;2(3):135-44. DOI:10.1007/s12602-010-9045-4][Burton JP, Cowley S, Simon RR, et al. Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study. Food Chem Toxicol. 2011;49(9):2356-64. DOI:10.1016/j.fct.2011.06.038][Di Pierro F, Risso P, Poggi E, et al. Use of Streptococcus salivarius K12 to reduce the incidence of pharyngo-tonsillitis and acute otitis media in children: a retrospective analysis in not-recurrent pediatric subjects. Minerva Pediatr. 2018;70(3):240-5. DOI:10.23736/S0026-4946.18.05182][Stašková A, Sondorová M, Nemcová R, et al. Antimicrobial and Antibiofilm Activity of the Probiotic Strain Streptococcus salivarius K12 against Oral Potential Pathogens. Antibiotics (Basel). 2021;10(7):793. DOI:10.3390/antibiotics10070793][Крючко Т.А., Ткаченко О.Я. Клинический опыт применения Streptococcus salivarius K12 в профилактике фаринготонзиллитов и респираторных инфекций у детей. Здоровье ребенка. 2018;7:629-34 [Kryuchko TO, Tkachenko OYa. Clinical experience of Streptococcus salivarius K12 use for the prevention of pharyngotonsillitis and respiratory infections in children. Zdorov'e rebenka. 2018;7:629-34 (in Russian)]. DOI:10.22141/2224-0551.13.7.2018.148915][Ильченко С.И., Фиалковская А.А., Можейко Т.В. О профилактике рекуррентных респираторных заболеваний у детей с микроаспирационным синдромом. Педиатрия. Восточная Европа. 2019;4:680-7. Режим доступа: https://www.elibrary.ru/item.asp?id=41411891. Ссылка активна на 26.05.2022 [Ilchenko SI, Fialkovskaia AA, Mozheiko TV. Prevention of recurrent respiratory diseases in children with microaspiration syndrome. Pediatrics. Eastern Europe. 2019;4:680-7. Available: https://www.elibrary.ru/item.asp?id=41411891. Accessed: 26.05.2022 (in Russian)].][Крамарев С.А., Евтушенко В.В. Бактоблис® (Streptococcus salivarius K12) – инновационная терапия и профилактика острых респираторных инфекций и их осложнений. Актуальная инфектология. 2020;1:50-3 [Kramarev SA, Yevtushenko VV. Bactoblis® (Streptococcus salivarius K12) – innovative therapy and prevention of acute respiratory infections and their complications. Aktual'naia infektologiia. 2020;1:50-3 (in Russian)]. DOI:10.22141/2312-413x.8.1.2020.196172][Ильченко С.И., Фиалковская А.А., Можейко Т.В. О профилактике рекуррентных респираторных заболеваний у детей с микроаспирационным синдромом. Оториноларингология. Восточная Европа. 2020;3:278-85 [Ilchenko SI, Fialkovskaia AA, Mozheiko TV. Prevention of recurrent respiratory diseases in children with microaspiration syndrome. Otorinolaringologiia. Vostochnaia Evropa. 2020;3:278-85 (in Russian)]. DOI:10.34883/PI.2020.10.3.051][Крючко Т.А., Ткаченко О.Я., Несина И.Н., и др. Пути оптимизации лечения детей с заболеваниями дыхательных путей и лор-органов. Педиатрия. Восточная Европа. 2021;3:482-91 [Kryuchko TA, Tkachenko OYa, Nesina IN, et al. Ways to Optimize the Treatment of Children with Diseases of the Respiratory Tract. Pediatriia. Vostochnaia Evropa. 2021;3:482-91 (in Russian)]. DOI:10.34883/PI.2021.9.3.015][Овчинников А.Ю., Мирошниченко Н.А., Егиян С.С., Акопян Л.В. Возможности пробиотической терапии при хронических воспалительных заболеваниях ротоглотки. Эффективная фармакотерапия. 2022;4:24-8 [Ovchinnikov AYu, Miroshnichenko NA, Egiyan SS, Akopyan LV. Possibilities of Probiotic Therapy in Chronic Inflammatory Diseases of the Oropharynx. Effektivnaia farmakoterapiia. 2022;4:24-8 (in Russian)]. DOI:10.33978/2307-3586-2022-18-4-24-28][Zupancic K, Kriksic V, Kovacevic I, Kovacevic D. Influence of Oral Probiotic Streptococcus salivarius K12 on Ear and Oral Cavity Health in Humans: Systematic Review. Probiotics Antimicrob Proteins. 2017;9(2):102-10. DOI:10.1007/s12602-017-9261-2][Wilcox CR, Stuart B, Leaver H, et al. Effectiveness of the probiotic Streptococcus salivarius K12 for the treatment and/or prevention of sore throat: a systematic review. Clin Microbiol Infect. 2019;25(6):673-80. DOI:10.1016/j.cmi.2018.12.031][Marini G, Sitzia E, Panatta ML, De Vincentiis GC. Pilot study to explore the prophylactic efficacy of oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngo-tonsillar episodes in pediatric patients. Int J Gen Med. 2019;12:213-7. DOI:10.2147/IJGM.S168209][Крамарев С.А., Евтушенко В.В., Серякова И.Ю., Каминская Т.Н. Применение пробиотического штамма Streptococcus salivarius K12 в лечении острых тонзиллофарингитов у детей. Актуальная инфектология. 2020;3-4:29-34 [Kramarov SO, Yevtushenko VV, Seryakova IYu, Kaminskaya TN. Application of Streptococcus salivarius K12 probiotic strain in the treatment of acute tonsillopharyngitis in children. Actual infectology. 2020;3-4:29-34 (in Russian)]. DOI:10.22141/2312-413x.8.3-4.2020.212657][Chen TY, Hale JDF, Tagg JR, et al. In vitro Inhibition of Clinical Isolates of Otitis Media Pathogens by the Probiotic Streptococcus salivarius BLIS K12. Probiotics Antimicrob Proteins. 2021;13(3):734-8. DOI:10.1007/s12602-020-09719-7][Ковалева А.Ю., Эйдельштейн И.А., Ковалева Н.С. Эффективность применения пробиотика бактоблис для профилактики заболеваний полости рта. В сборнике: Актуальные проблемы детской стоматологии и ортодонтии. Сборник научных статей XI международной научно-практической конференции по детской стоматологии в рамках IV Дальневосточного Стоматологического конгресса. Хабаровск, 2021; c. 101-4. Режим доступа: https://www.elibrary.ru/item.asp?id=48267079. Ссылка активна на 26.05.2022 [Kovaleva A.Iu., Eidel'shtein I.A., Kovaleva N.S. Effektivnost' primeneniia probiotika baktoblis dlia profilaktiki zabolevanii polosti rta. V sbornike: Aktual'nye problemy detskoi stomatologii i ortodontii. Sbornik nauchnykh statei XI mezhdunarodnoi nauchno-prakticheskoi konferentsii po detskoi stomatologii v ramkakh IV Dal'nevostochnogo Stomatologicheskogo kongressa. Khabarovsk, 2021; p. 101-4. Available: https://www.elibrary.ru/item.asp?id=48267079. Accessed: 26.05.2022 (in Russian)].][Караков К.Г., Власова Т.Н., Оганян А.В., и др. Критерии выбора метода коррекции дисбактериоза органов полости рта. Проблемы стоматологии. 2020;2:17-21 [Karakov KG, Vlasova TN, Oganyan AV, et al. Criteria for choosing the method of correction of disbacteriosis of authorities oral cavity. Problemy stomatologii. 2020;2:17-21 (in Russian)]. DOI:10.18481/2077-7566-20-16-2-17-21][Li Y, Shao F, Zheng S, et al. Alteration of Streptococcus salivarius in Buccal Mucosa of Oral Lichen Planus and Controlled Clinical Trial in OLP Treatment. Probiotics Antimicrob Proteins. 2020;12(4):1340-8. DOI:10.1007/s12602-020-09664-5][He L, Yang H, Chen Z, Ouyang X. The Effect of Streptococcus salivarius K12 on Halitosis: a Double-Blind, Randomized, Placebo-Controlled Trial. Probiotics Antimicrob Proteins. 2020;12(4):1321-9. DOI:10.1007/s12602-020-09646-7][Mokhtar M, Rismayuddin NAR, Mat Yassim AS, et al. Streptococcus salivarius K12 inhibits Candida albicans aggregation, biofilm formation and dimorphism. Biofouling. 2021;37(7):767-76. DOI:10.1080/08927014.2021.1967334][Burton JP, Chilcott CN, Tagg JR. The rationale and potential for the reduction of oral malodour using Streptococcus salivarius probiotics. Oral Dis. 2005;11(Suppl. 1):29-31. DOI:10.1111/j.1601-0825.2005.01084.x][Masdea L, Kulik EM, Hauser-Gerspach I, et al. Antimicrobial activity of Streptococcus salivarius K12 on bacteria involved in oral malodour. Arch Oral Biol. 2012;57(8):1041-7. DOI:10.1016/j.archoralbio.2012.02.011][Савлевич Е.Л., Дорощенко Н.Э., Жарких М.А., и др. Коррекция галитоза при хронических воспалительных заболеваниях ротоглотки у взрослых. Вестник оториноларингологии. 2021;6:41-6 [Savlevich EL, Doroshchenko NE, Zharkikh MA, et al. Correction of halitosis in chronic inflammatory diseases of the oropharynx in adults. 2021;6:41-6 (in Russian)]. DOI:10.17116/otorino20218606141][Burton JP, Wescombe PA, Moore CJ, et al. Safety assessment of the oral cavity probiotic Streptococcus salivarius K12. Appl Environ Microbiol. 2006;72(4):3050-3. DOI:10.1128/AEM.72.4.3050-3053.2006][Sarlin S, Tejesvi MV, Turunen J, et al. Impact of Streptococcus salivarius K12 on Nasopharyngeal and Saliva Microbiome: A Randomized Controlled Trial. Pediatr Infect Dis J. 2021;40(5):394-402. DOI:10.1097/INF.0000000000003016][Hale JDF, Jain R, Wescombe PA, et al. Safety assessment of Streptococcus salivarius M18 a probiotic for oral health. Benef Microbes. 2022;13(1):47-60. DOI:10.3920/BM2021.0107][Di Pierro F, Zanvit A, Nobili P, et al. Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study. Clin Cosmet Investig Dent. 2015;7:107-13. DOI:10.2147/CCIDE.S93066.][Кисельникова Л.П., Царев В.Н., Тома Э.И., Подпорин М.С. Клинико-микробиологическая характеристика микробиоценоза полости рта детей и возможности его коррекции с применением пробиотиков на основе саливарных стрептококков. Клиническая стоматология. 2021;4:24-9 [Kisel'nikova LP, Tsarev VN, Toma EI, Podporin MS. Kliniko-mikrobiologicheskaia kharakteristika mikrobiotsenoza polosti rta detei i vozmozhnosti ego korrektsii s primeneniem probiotikov na osnove salivarnykh streptokokkov. Klinicheskaia stomatologiia. 2021;4:24-9 (in Russian)]. DOI:10.37988/1811-153X_2021_4_24][Tunçer S, Karaçam S. Cell-free supernatant of Streptococcus salivarius M18 impairs the pathogenic properties of Pseudomonas aeruginosa and Klebsiella pneumonia. Arch Microbiol. 2020;202(10):2825-40. DOI:10.1007/s00203-020-02005-8][Karaçam S, Tunçer S. Exploiting the Acidic Extracellular pH: Evaluation of Streptococcus salivarius M18 Postbiotics to Target Cancer Cells. Probiotics Antimicrob Proteins. 2021. DOI:10.1007/s12602-021-09806-3][Burton JP, Drummond BK, Chilcott CN, et al. Influence of the probiotic Streptococcus salivarius strain M18 on indices of dental health in children: a randomized double-blind, placebo-controlled trial. J Med Microbiol. 2013;62(Pt 6):875-84. DOI:10.1099/jmm.0.056663-0][Bardellini E, Amadori F, Gobbi E, et al. Does Streptococcus Salivarius Strain M18 Assumption Make Black Stains Disappear in Children? Oral Health Prev Dent. 2020;18(1):161-4. DOI:10.3290/j.ohpd.a43359][Gobbi E, De Francesco MA, Piccinelli G, et al. In vitro inhibitory effect of two commercial probiotics on chromogenic actinomycetes. Eur Arch Paediatr Dent. 2020;21(6):673-7. DOI:10.1007/s40368-020-00512-2][Гажва С.И., Белоусова Е.Ю. Особенности лечения стоматологических заболеваний у детей с расстройствами аутистического спектра на фоне дисбиозов.В сборнике: Стоматологическая весна в Белгороде – 2021. Сборник трудов Международной научной конференции молодых ученых, работающих в области стоматологии, приуроченная к году науки и технологий. Белгород, 2021; с. 36-7. Режим доступа: https://elibrary.ru/item.asp?id=48509394. Ссылка активна на 26.05.2022 [Gazhva SI, Belousova EYu. Features of the treatment of dental diseases in children with autism spectrum disorders against the background of dysbiosis. In the collection: Dental Spring in Belgorod – 2021. Proceedings of the International Scientific Conference of Young Scientists Working in the Field of Dentistry, dedicated to the year of science and technology. Belgorod, 2021; p. 36-7. Available: https://elibrary.ru/item.asp?id=48509394. Accessed: 26.05.2022 (in Russian)].][Benic GZ, Farella M, Morgan XC, et al. Oral probiotics reduce halitosis in patients wearing orthodontic braces: a randomized, triple-blind, placebo-controlled trial. J Breath Res. 2019;13(3):036010. DOI:10.1088/1752-7163/ab1c81][Кравец О.Н., Дерябина Л.В. Клиническая оценка эффективности применения пробиотика на основе Streptococcus salivarius M18 при лечении хронического генерализованного пародонтита легкой степени тяжести. Проблемы медицинской микологии. 2021;23(2):96. Режим доступа: https://elibrary.ru/item.asp?id=46212960. Ссылка активна на 26.05.2022 [Kravets ON, Deryabina LV. Clinical evaluation of the effectiveness of probiotics based on Streptococcus salivarius M18 in treatment of periodontal diseases. Problems of medical mycology. 2021;23(2):96. Available: https://elibrary.ru/item.asp?id=46212960. Accessed: 26.05.2022 (in Russian)].][Manning J, Dunne EM, Wescombe PA, et al. Investigation of Streptococcus salivarius-mediated inhibition of pneumococcal adherence to pharyngeal epithelial cells. BMC Microbiol. 2016;16(1):225. DOI:10.1186/s12866-016-0843-z][Yoo HJ, Jwa SK, Kim DH, Ji YJ. Inhibitory effect of Streptococcus salivarius K12 and M18 on halitosis in vitro. Clin Exp Dent Res. 2020;6(2):207-14. DOI:10.1002/cre2.269][MacDonald KW, Chanyi RM, Macklaim JM, et al. Streptococcus salivarius inhibits immune activation by periodontal disease pathogens. BMC Oral Health. 2021;21(1):245. DOI:10.1186/s12903-021-01606-z][Poorni S, Nivedhitha MS, Srinivasan M, Balasubramaniam A. Effect of Probiotic Streptococcus salivarius K12 and M18 Lozenges on the Cariogram Parameters of Patients With High Caries Risk: A Randomised Control Trial. Cureus. 2022;14(3):e23282. DOI:10.7759/cureus.23282][Jansen PM, Abdelbary MMH, Conrads G. A concerted probiotic activity to inhibit periodontitis-associated bacteria. PLoS One. 2021;16(3):e0248308. DOI:10.1371/journal.pone.0248308][Borsche L, Glauner B, von Mendel J. COVID-19 Mortality Risk Correlates Inversely with Vitamin D3 Status, and a Mortality Rate Close to Zero Could Theoretically Be Achieved at 50 ng/mL 25(OH)D3: Results of a Systematic Review and Meta-Analysis. Nutrients. 2021;13(10):3596. DOI:10.3390/nu13103596][Varikasuvu SR, Thangappazham B, Vykunta A, et al. COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials. Expert Rev Anti Infect Ther. 2022;20(6):907-13. DOI:10.1080/14787210.2022.2035217][Cui X, Zhai Y, Wang S, et al. Effect of the COVID-19 Pandemic on Serum Vitamin D Levels in People Under Age 18 Years: A Systematic Review and Meta-Analysis. Med Sci Monit. 2022;28:e935823. DOI:10.12659/MSM.935823][Youssef M, Ahmed HY, Zongo A, et al. Probiotic Supplements: Their Strategies in the Therapeutic and Prophylactic of Human Life-Threatening Diseases. Int J Mol Sci. 202;22(20):11290. DOI:10.3390/ijms222011290][Cunningham M, Azcarate-Peril MA, Barnard A, et al. Shaping the Future of Probiotics and Prebiotics. Trends Microbiol. 2021;29(8):667-85. DOI:10.1016/j.tim.2021.01.003]