Oral Health Group

COVID-19: Current Overview on SARS-CoV-2 and the Dental Implications

July 11, 2022
by Miriam Ting, DMD, MS; Jon B. Suzuki, DMD, PHD, MBA


Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported December 31, 2019, to the China Ministry of Health and the World Health Organization (WHO). It started in Wuhan, China, and is highly contagious. The spread was rapid, and it was declared a global emergency on January 30, 2020 and global pandemic on March 11, 2020. SARS-CoV-2 transmits via droplet, aerosol, oral-fecal routes,1 as well as contact with contaminated surfaces and oral fluids.2 Dentists and healthcare professionals are at risk of exposure to SARS-CoV-2 during daily patient care. Dental and medical offices are at risk for patient and healthcare provider cross infection.3 Thus, personal protective equipment (PPE) like masks, face shields, and gowns, as well as hand washing and pre-treatment mouth rinsing are adopted in the dental and medical facilities to curb the spread of COVID-19.4

Systemic consequences

COVID-19 clinical symptoms included fever, myalgia, fatigue, dry cough, sore throat, diarrhea,5,6 and loss of taste;7 symptoms appear about 5.2 days after infection.8 Most clinical presentations are asymptomatic or mild; less than 5% develop multi-organ failure or acute respiratory distress syndrome (ARDS). In an epidemiologic study, 17% of COVID-19 patients were asymptomatic and COVID-19 transmission in asymptomatic and symptomatic patients was statistically similar.9 SARS-CoV-2 is highly contagious, colonizing nasal, oral and pharyngeal mucosa.10 Advanced age, hypertension, diabetes, heart disease, and obesity were risk factors for SARS-CoV-2 .11-13 Severe complications included blood clots, septic shock, pneumonia, sepsis, and ARDS.14 Respiratory viral infections can increase susceptibility to inflammatory lung damage and bacterial superinfections.15 The likely cause of death were post-viral complications, like ARDS, rather than the initial viral infection.


Antibody response to SARS-CoV-2 peaks at 14-21 days after signs of infection.16 Exposure to SARS-CoV-2 appears to stimulate increased levels neutralizing secretory antibodies. Immunoglobulin A (IgA) dominates the initial mucosal immune response in the oral cavity.17 In mild COVID-19 infection, recovery is approximately 2 weeks. For severe infection, recovery could extend 3-6 weeks and can persist beyond 4 weeks to develop into long COVID.18 Long COVID or post-COVID-19 syndrome was highest in patients aged 24-36 years and in females. COVID-19-related systemic conditions involving multiple organs may persist during long COVID,19 increasing risks of encephalitis and strokes. These symptoms for COVID-19 and long COVID may manifest as fever, coughing, breathlessness, fatigue, brain fog, depression, psychosis, anxiety, myocarditis, arrhythmias, heart damage, and muscle and joint pain.20,21 Smell and taste are frequently altered or impaired.21 Furthermore, the increased inflammatory cytokine activation triggered by SARS-CoV-2 can cause prolonged damage to the immune system.22 Seniors over 70 years have the highest morbidity and mortality,23 while children have significantly less morbidity.24 Immuno-senescence or age-related immunity effects may contribute to increased mortality in the older age group. Some of the effects of immuno-senescence on innate/adaptive immunity may include increased lymphocyte response impairment,25 cytokine secretion,26 failed antibody production, ineffective T-cell response, and severe organ dysfunction from inflammation,27 increasing SARS-CoV-2 susceptibility and COVID-19 severity, and reducing vaccine responses.


SARS-CoV-2 is single stranded RNA with cell-surface spike glycoproteins enabling penetration and adherence to host cells.28 (Fig. 1) The primary receptor for the SARS-CoV-2 spike glycoprotein is the angiotensin-converting enzyme 2 (ACE-2) receptor found in the lungs, myocardial cells, kidneys, tongue, and salivary glands.

Fig. 1

 Basic structure of SARS-CoV-2.

Basic structure of SARS-CoV-2.

The disease progression can be described in 3 main stages:

Stage 1 Innate immunity activation
Stage 2 Adaptive immunity activation
Stage 3 Cytokine release syndrome (“cytokine storm”)29

The hyper-responsive host produces an exaggerated cytokine release30,31 resulting in a cytokine storm. (Fig. 2) This proinflammatory cytokine release is intensified by increased vascular permeability and effector cells infiltration, inducing excessive monocyte proliferation and lymphocyte apoptosis, possibly resulting in immunodeficiency states32 that manifest as shock, multiple organ dysfunction, hypercoagulation, and acute lung injury.29 The dysregulation and elevated production of acute proinflammatory cytokines (including IFN-γ, IFN-γ-induced protein 10, IL-1, IL-6, IL-12, and monocyte chemoattractant protein36) can cause multi-organ failure, particularly kidneys and heart.33-35 The IL-6 levels in SARS-CoV-2 non-survivors were higher than in the survivors.31 IL-6 has also been associated with the severity of the SARS-CoV-2 infection,37-41 and the increased mortality of older patients and patients with comorbidities.42

Fig. 2

Potential pathogenesis of SARS-CoV-2 in the pulmonary tree.

Potential pathogenesis of SARS-CoV-2 in the pulmonary tree.

Periodontal inflammation and other chronic inflammatory diseases may influence susceptibility to COVID-19. (Fig. 3) Three different clinical responses of the periodontium to bacterial burden, designated as “high”, “low”, and “slow”, have been identified. The clinical responses to bacteria reflect clinical responses to SARS-CoV-2 virus challenges in the oral cavity. The “high” response group to microbial plaque has clinically high IL-1β levels in inflamed gingival tissues. High clinical gingival responses in gingiva may include patients who were previously referred to as “Aggressive or Early Onset Periodontitis” (now designated as Stage II, III, or IV Grade C Rapid Rate Periodontitis by the new American Academy of Periodontology – European Federation of Periodontology Classification).43

Fig. 3

Potential immune reactions to SARS-CoV-2.

Potential immune reactions to SARS-CoV-2.

Low Clinical gingival responses to microbial plaque may include patients who may be relatively resistant clinically to accumulations of bacterial burden around the dentition and soft tissues (now designated as Stage I, Grade A slow rate).43

Slow Clinical responses to microbial plaque may include patients who were previously designated as “Chronic or Adult” forms of Periodontitis (now designated as Stages I, II, or III, Grade A).43

Although it may be argued that the gingiva responds differently to viral challenges as compared to bacterial challenges, varying degrees of inflammatory response for non-vaccinated SARS-CoV-2-infected patients may be at varying levels of risk, from hospitalizations to possible death.

COVID-19 vaccines

The ideal vaccine should be effective after 1-2 doses, protect for at least 6 months, and reduce viral transmission if infected. According to the US Food and Drug Administration (FDA), a vaccine should have at least 50% vaccine efficacy.44 Randomized controlled trials for vaccine efficacy evaluated infection reduction, clinical disease severity reduction, and infectivity duration reduction.45 Vaccine protection is proportional to infection reduction between vaccinated subjects and control. However, other factors may interfere with the data. These factors include socioeconomic conditions (conditions representing strata of social classes reflecting potential differences in access to dental care, personal oral health habits, and living conditions) (representing urban, rural, or other areas of the country), geographical settings, age differences, and herd immunity.

There are varied SARS-CoV-2 vaccine approaches,46 including targeting nucleic acid/m-RNA, spike proteins (protein subunits), adenovirus carrier (viral vector), and inactivated (whole) virus, aiming at neutralizing the spike protein, mRNA, or inactivated virus.47 Clinical trials for SARS-CoV-2 vaccines investigated the neutralizing antibody response for the following vaccines: mRNA,48,49 adenoviral vector,50,51 spike glycoprotein52 with adjuvants, and inactivated virus.53,54 An effective vaccine should prevent infection, disease progression or transmission, with reduced mortality and disease severity the desired outcome. The major vaccines available worldwide are outlined in Table 1.

Diminishing immunologic memory and/or mutating antigenicity may decrease vaccine efficacy over time. Vaccine boosters (multiple vaccinations or multiple vaccine types) can prolong protection may induce robust and longer lasting immunity.55,56 The CDC reported that vaccine effectiveness decreased in selected medically compromised groups, resulting in higher risks of COVID-19 breakthrough infections57 and breakthrough infections in fully vaccinated patients.58 Vaccines may reduce breakthrough infections significantly, and United Kingdom data59 indicated that fully vaccinated patients were at a reduced risk for severe complications, breakthrough infections, and developing long-haul COVID.

Dental and oral implications

For cellular entry, the SARS-CoV-2 uses the ACE-2 receptors,60 and its infectivity is dependent on its ability to penetrate the cell. ACE-2 receptors are found in oral mucosa at the floor of the mouth, buccal mucosa, gingiva, and the tongue.61 SARS-CoV-2 can target the ACE-2-positive taste organs on the tongue61 may, causing the commonly reported loss of taste .7,61-63 Similarly, ACE-2-positive salivary glands may be targeted, causing salivary dysfunction,64 dry mouth,7 and SARS-CoV-2 detectability in saliva.65 There ae more ACE-2 receptors in salivary glands than in the lungs, and the salivary glands may harbor SARS-CoV-2 in asymptomatic patients.66 ACE-2 receptors in chronic periodontitis fibroblasts with elevated protease levels67 may increase the risk for viral entry.68

SARS-CoV-2 fusion to the host cell requires S protein cleavage by transmembrane protease serine 2 (TMPRSS2) or furin,69-71 available from oral pathogenic bacteria.72

Oral health can affect overall health (73), and may be related to the increased/decreased COVID-19 risk.61,66 A healthy oral cavity has a symbiotic balance of gram+ bacteria. Periodontal disease and poor oral hygiene promote dysbiotic biofilms that can trigger cytokine release which may have systemic repercussions, and may propagate pulmonary infections.74 Furthermore, aspired oral pathogenic bacteria may exacerbate lung infections,75 leading to inflammation and aggravation of COVID-19.72 Mortality in severely affected COVID-19 patients was due to secondary bacterial infection rather than SARS-CoV-2.12 This is supported by the higher neutrophil to lymphocyte ratio detected in COVID-19 patients, indicative of a bacterial, rather than viral, superinfection.76 This factor is significant in the elderly and medically-compromised, where the poor swallowing reflex may increase the risk of bacterial aspiration,77 increasing COVID-19 severity.78,79 Periodontal pathogens have been found in the lower respiratory tract and lungs of COVID-19 patients.80

Periodontitis and poor oral hygiene increase periodontal pathogens, raising ACE-2 expression, increasing proinflammatory cytokine release, and degrading the SARS-CoV-2 S-protein. These pathogens upregulate ACE-2 transcription, induce alveolar epithelial cell IL-8 and IL-6 production,81 and degrade S protein by microbial proteases,70,71 increasing SARS-CoV-2 infectivity and penetration. Prolonged COVID-19 hospitalization risks poor oral care access, increasing the risk of aspirated pathogenic oral bacteria causing lung inflammation. Thus, periodontitis and poor oral hygiene (increased oral pathogenic bacteria) may contribute to COVID-19 progression,72 and may increase morbidity. Periodontitis, when associated with comorbidities(diabetes mellitus, chronic obstructive pulmonary disease, hypertension, and cerebrovascular or cardiovascular disease), can worsen COVID-19 outcomes.82 Diabetes and cardiovascular disease were the most prevalent comorbidities in COVID-19 hospitalizations.83 COVID-19 patients with periodontitis had a higher mortality risk than non-periodontitis patients.84 In addition, periodontitis increased IL-1 and TNF cytokine release exacerbating the “cytokine storms“ in COVID-19 patients. Higher cytokine levels elevated COVID risk. The reduction of periodontitis-induced cytokines may lower the risk of SAR-CoV-2 mortality.

Meticulous daily oral hygiene maintenance and periodontitis treatment reduces gingival inflammation, ACE-2 expression, inflammatory cytokines, and aspiration pneumonia,85 and may reduce COVID-19 susceptibility and aggravation.72 Periodontitis therapy and attention to oral health mitigates systemic diseases (diabetes, COPD),86,87 and may reduce pneumonia and influenza mortality and complications.88,89

Pre-procedural oral antiseptic rinses are effective in reducing bacterial cross-infection risk in aerosols.90 Oral antiseptics reported antiviral activity in vitro.91 Oral antiseptics disrupt the viral lipid envelope interfering with viral integrity.91 Oral antiseptics active in viral cross-contamination prevention include: 0.05-0.10% cetylpyridinium chloride,92 1% povidone-iodine,93 0.12% chlorhexidine,94 beta-cyclodextrin with citrox,95 1% hydrogen peroxide,96 and essential oil mouth rinses (e.g., eucalyptol, thymol, menthol, methyl salicylate).97 Mouth rinse combination of 1% hydrogen peroxide and 0.2-0.3% chlorhexidine in sequence can also be beneficial,98 reducing salivary viral load and decreasing SARS-CoV-2 transmission.99

A randomized control clinical trial investigated antimicrobial mouth rinse viral load reduction in asymptomatic SAR-CoV-2 patients100 with chlorhexidine (0.12%), povidone iodine (0.5%), and hydrogen peroxide (1%), with sterile saline as a control. All 4 mouth rinses and the saline control decreased viral load indicating that antimicrobial pre-rinsing may be effective in reducing salivary viral cross-contamination in the dental practice. The limitation: SARS-CoV-2 viral loads were investigated, excluding other respiratory viruses and oral bacteria.

Oral cavity bacterial/viral load in aerosol sprays generated from dental and hygiene procedures has long been of concern. This study suggests that povidone iodine and hydrogen peroxide, together with chlorohexidine may be an effective antiviral rinse. Another study suggests that povidone iodine, cetypyridinium chloride, and chlorohexidine have effective anti-SARS-CoV-2 activity.96 However, long-term bioactivity and substantivity of these rinses must be considered. Antimicrobial mouthwashes or nasal sprays in symptomatic or asymptomatic COVID-19 patients may prevent viral cross-infection and protect healthcare professionals.101


Good periodontal health and optimal oral hygiene habits may contribute to increased survival with SARS-CoV-2. In addition, good systemic health and optimal oral health may contribute to the prevention of COVID-19 infections. Antimicrobial mouth rinses may be recognized as routine therapeutic agents to inhibit the transmission of COVID-19 in the dental office.

Oral Health welcomes this original article.


  1. Khan S, Liu J, Xue M. Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns. Front Med (Lausanne). 2020;7:310.
  2. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020;382(16):1564-7.
  3. Souza RC, Costa PS, Costa LR. Dental sedation precautions and recommendations during the COVID-19 pandemic. Braz J Dent. 2020;77:1-3.
  4. Ting M, Suzuki JB. SARS-CoV-2: Overview and Its Impact on Oral Health. Biomedicines. 2021;9(11):1690.
  5. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020;109:102433.
  6. Greenland JR, Michelow MD, Wang L, London MJ. COVID-19 Infection: Implications for Perioperative and Critical Care Physicians. Anesthesiology. 2020;132(6):1346-61.
  7. Chen L, Zhao J, Peng J, Li X, Deng X, Geng Z, et al. Detection of SARS-CoV-2 in saliva and characterization of oral symptoms in COVID-19 patients. Cell Prolif. 2020;53(12):e12923.
  8. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020;382(13):1199-207.
  9. Chen Y, Wang AH, Yi B, Ding KQ, Wang HB, Wang JM, et al. [Epidemiological characteristics of infection in COVID-19 close contacts in Ningbo city]. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(5):667-71.
  10. Wolfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Muller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465-9.
  11. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33.
  12. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62.
  13. Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J, Duhamel A, et al. High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation. Obesity (Silver Spring). 2020;28(7):1195-9.
  14. World Health Organization. Clinical Management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected. 2020.
  15. Cox MJ, Loman N, Bogaert D, O’Grady J. Co-infections: potentially lethal and unexplored in COVID-19. Lancet Microbe. 2020;1(1):e11.
  16. Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26(6):845-8.
  17. Sterlin D, Fadlallah J, Adams O, Fieschi C, Parizot C, Dorgham K, et al. Human IgA binds a diverse array of commensal bacteria. J Exp Med. 2020;217(3).
  18. World Health Organization. Coronavirus Disease 2019 (COVID-19) Situation Report – 46. 2019.
  19. Temgoua MN, Endomba FT, Nkeck JR, al. e. Coronavirus Disease 2019 (COVID-19) as a Multi-Systemic Disease and its Impact in Low- and Middle-Income Countries (LMICs). SN Compr Clin Med. 2020;2:1377–87.
  20. Couzin-Frankel J. The long haul. Science. 2020;369(6504):614-7.
  21. Wadman M, Couzin-Frankel J, Kaiser J, Matacic C. A rampage through the body. Science. 2020;368(6489):356-60.
  22. Wu Y, Huang X, Sun J, Xie T, Lei Y, Muhammad J, et al. Clinical Characteristics and Immune Injury Mechanisms in 71 Patients with COVID-19. mSphere. 2020;5(4).
  23. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
  24. Dong Y, Mo X, Hu Y, al. e. Epidemiology of COVID-19 among children in China. Pediatrics. 2020;145(6).
  25. Kovtonyuk LV, Fritsch K, Feng X, Manz MG, Takizawa H. Inflamm-Aging of Hematopoiesis, Hematopoietic Stem Cells, and the Bone Marrow Microenvironment. Front Immunol. 2016;7:502.
  26. Fulop T, Larbi A, Dupuis G, Le Page A, Frost EH, Cohen AA, et al. Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes? Front Immunol. 2017;8:1960.
  27. Cunha LL, Perazzio SF, Azzi J, Cravedi P, Riella LV. Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response. Front Immunol. 2020;11:1748.
  28. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020;183(6):1735.
  29. Calabrese LH, Lenfant T, Calabrese C. Interferon therapy for COVID-19 and emerging infections: Prospects and concerns. Cleve Clin J Med. 2020.
  30. Siu KL, Yuen KS, Castano-Rodriguez C, Ye ZW, Yeung ML, Fung SY, et al. Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC. FASEB J. 2019;33(8):8865-77.
  31. Tay MZ, Poh CM, Renia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363-74.
  32. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76(1):16-32.
  33. Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med. 2020;8(6):e46-e7.
  34. Perico L, Benigni A, Remuzzi G. Should COVID-19 Concern Nephrologists? Why and to What Extent? The Emerging Impasse of Angiotensin Blockade. Nephron. 2020;144(5):213-21.
  35. Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, et al. [A pathological report of three COVID-19 cases by minimal invasive autopsies]. Zhonghua Bing Li Xue Za Zhi. 2020;49(5):411-7.
  36. Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004;136(1):95-103.
  37. Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J, et al. [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020;43(3):203-8.
  38. McGonagle D, Sharif K, O’Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020;19(6):102537.
  39. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58(7):1021-8.
  40. Ulhaq ZS, Soraya GV. Interleukin-6 as a potential biomarker of COVID-19 progression. Med Mal Infect. 2020;50(4):382-3.
  41. Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020;55(5):105954.
  42. Adriaensen W, Mathei C, Vaes B, van Pottelbergh G, Wallemacq P, Degryse JM. Interleukin-6 as a first-rated serum inflammatory marker to predict mortality and hospitalization in the oldest old: A regression and CART approach in the BELFRAIL study. Exp Gerontol. 2015;69:53-61.
  43. Bamashmous S, Kotsakis GA, Kerns KA, Leroux BG, Zenobia C, Chen D, et al. Human variation in gingival inflammation. Proc Natl Acad Sci U S A. 2021;118(27).
  44. U.S. Food and Drug Administration. Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry. 2020.
  45. Weinberg GA, Szilagyi PG. Vaccine epidemiology: efficacy, effectiveness, and the translational research roadmap. J Infect Dis. 2010;201(11):1607-10.
  46. Wang J, Peng Y, Xu H, Cui Z, Williams RO, 3rd. The COVID-19 Vaccine Race: Challenges and Opportunities in Vaccine Formulation. AAPS PharmSciTech. 2020;21(6):225.
  47. Thanh LT, Andreadakis Z, Kumar A, al. E. The COVID-19 vaccine development landscape. Nat Rev Drug Discov. 2020;19:305-06.
  48. Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, et al. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N Engl J Med. 2020;383(25):2427-38.
  49. Walsh EE, Frenck RW, Jr., Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020;383(25):2439-50.
  50. Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2020;396(10249):479-88.
  51. Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Shcheblyakov DV, Dzharullaeva AS, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020;396(10255):887-97.
  52. Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020;383(24):2320-32.
  53. Xia S, Duan K, Zhang Y, Zhao D, Zhang H, Xie Z, et al. Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. JAMA. 2020;324(10):951-60.
  54. Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis. 2021;21(1):39-51.
  55. Tatsis N, Ertl HC. Adenoviruses as vaccine vectors. Mol Ther. 2004;10(4):616-29.
  56. Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Dzharullaeva AS, Tukhvatulina NM, Shcheblyakov DV, et al. Safety and immunogenicity of GamEvac-Combi, a heterologous VSV- and Ad5-vectored Ebola vaccine: An open phase I/II trial in healthy adults in Russia. Hum Vaccin Immunother. 2017;13(3):613-20.
  57. Tenforde MW, Olson SM, Self WH, Talbot HK, Lindsell CJ, Steingrub JS, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged >/=65 Years – United States, January-March 2021. MMWR Morb Mortal Wkly Rep. 2021;70(18):674-9.
  58. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report (MMWR). Outbreak of SARs-Cov-2 Infections, including COVID-19 Vaccine breakthrough infections, associated with large public gatherings- Barnstable County, Massachusetts. 2021;70(31):1059-62.
  59. Antonelli M, Penfold RS, Merino J, Sudre CH, Molteni E, Berry S, et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect Dis. 2021.
  60. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.
  61. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):8.
  62. Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, et al. Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study. Clin Infect Dis. 2020;71(15):889-90.
  63. Fischer W, Eron JJ, Holman W, Cohen MS, Fang L, Szewczyk LJ, et al. Molnupiravir, an Oral Antiviral Treatment for COVID-19. medRxiv. 2021.
  64. Liu L, Wei Q, Alvarez X, Wang H, Du Y, Zhu H, et al. Epithelial cells lining salivary gland ducts are early target cells of severe acute respiratory syndrome coronavirus infection in the upper respiratory tracts of rhesus macaques. J Virol. 2011;85(8):4025-30.
  65. To KK, Tsang OT, Yip CC, Chan KH, Wu TC, Chan JM, et al. Consistent Detection of 2019 Novel Coronavirus in Saliva. Clin Infect Dis. 2020;71(15):841-3.
  66. 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.
  67. Santos CF, Morandini AC, Dionisio TJ, Faria FA, Lima MC, Figueiredo CM, et al. Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue. PLoS One. 2015;10(8):e0134601.
  68. Madapusi Balaji T, Varadarajan S, Rao USV, Raj AT, Patil S, Arakeri G, et al. Oral cancer and periodontal disease increase the risk of COVID 19? A mechanism mediated through furin and cathepsin overexpression. Med Hypotheses. 2020;144:109936.
  69. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-80 e8.
  70. Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020;11(1):1620.
  71. Izaguirre G. The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases. Viruses. 2019;11(9).
  72. Takahashi Y, Watanabe N, Kamio N, Kobayashi R, Iinuma T, Imai K. Aspiration of periodontopathic bacteria due to poor oral hygiene potentially contributes to the aggravation of COVID-19. J Oral Sci. 2020;63(1):1-3.
  73. Oral health in America: a report of the Surgeon General. J Calif Dent Assoc. 2000;28(9):685-95.
  74. Scannapieco FA. Role of oral bacteria in respiratory infection. J Periodontol. 1999;70(7):793-802.
  75. Paju S, Scannapieco FA. Oral biofilms, periodontitis, and pulmonary infections. Oral Dis. 2007;13(6):508-12.
  76. Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020;17(5):533-5.
  77. Yamaya M, Yanai M, Ohrui T, Arai H, Sasaki H. Interventions to prevent pneumonia among older adults. J Am Geriatr Soc. 2001;49(1):85-90.
  78. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42.
  79. Wang B, Li R, Lu Z, Huang Y. Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis. Aging. 2020;12:6049-57.
  80. Shen Z, Xiao Y, Kang L, Ma W, Shi L, Zhang L, et al. Genomic Diversity of Severe Acute Respiratory Syndrome-Coronavirus 2 in Patients With Coronavirus Disease 2019. Clin Infect Dis. 2020;71(15):713-20.
  81. Takahashi Y, Watanabe N, Kamio N, Yokoe S, Suzuki R, Sato S, et al. Expression of the SARS-CoV-2 Receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium Fusobacterium nucleatum in Human Respiratory Epithelial Cells. Int J Mol Sci. 2021;22(3).
  82. Pitones-Rubio V, Chávez-Cortez EG, Hurtado-Camarena A, al. e. Is periodontal disease a risk factor for severe COVID-19 illness? 2020;144.
  83. Centers for Disease Control and Prevention. People of any age with underlying medical conditions. Available online: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html (accessed on 5 October 2021).
  84. 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.
  85. Suzuki JB, Delisle AL. Pulmonary actinomycosis of periodontal origin. J Periodontol. 1984;55(10):581-4.
  86. Abe S, Ishihara K, Adachi M, Sasaki H, Tanaka K, Okuda K. Professional oral care reduces influenza infection in elderly. Arch Gerontol Geriatr. 2006;43(2):157-64.
  87. Katagiri S, Nitta H, Nagasawa T, Uchimura I, Izumiyama H, Inagaki K, et al. Multi-center intervention study on glycohemoglobin (HbA1c) and serum, high-sensitivity CRP (hs-CRP) after local anti-infectious periodontal treatment in type 2 diabetic patients with periodontal disease. Diabetes Res Clin Pract. 2009;83(3):308-15.
  88. Yoneyama T, Yoshida M, Matsui T, Sasaki H. Oral care and pneumonia. Oral Care Working Group. Lancet. 1999;354(9177):515.
  89. 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;41(6):564-72.
  90. Marui VC, Souto MLS, Rovai ES, Romito GA, Chambrone L, Pannuti CM. Efficacy of preprocedural mouthrinses in the reduction of microorganisms in aerosol: A systematic review. J Am Dent Assoc. 2019;150(12):1015-26 e1.
  91. Eggers M, Koburger-Janssen T, Eickmann M, Zorn J. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens. Infect Dis Ther. 2018;7(2):249-59.
  92. Popkin DL, Zilka S, Dimaano M, Fujioka H, Rackley C, Salata R, et al. Cetylpyridinium Chloride (CPC) Exhibits Potent, Rapid Activity Against Influenza Viruses in vitro and in vivo. Pathog Immun. 2017;2(2):252-69.
  93. Eggers M. Infectious Disease Management and Control with Povidone Iodine. Infect Dis Ther. 2019;8(4):581-93.
  94. Karpinski TM, Szkaradkiewicz AK. Chlorhexidine – pharmaco-biological activity and application. Eur Rev Med Pharmacol Sci. 2015;19(7):1321-6.
  95. Carrouel F, Conte MP, Fisher J, Goncalves LS, Dussart C, Llodra JC, et al. COVID-19: A Recommendation to Examine the Effect of Mouthrinses with beta-Cyclodextrin Combined with Citrox in Preventing Infection and Progression. J Clin Med. 2020;9(4).
  96. Ren YF, Rasubala L, Malmstrom H, Eliav E. Dental Care and Oral Health under the Clouds of COVID-19. JDR Clin Trans Res. 2020;5(3):202-10.
  97. Meiller TF, Silva A, Ferreira SM, Jabra-Rizk MA, Kelley JI, DePaola LG. Efficacy of Listerine Antiseptic in reducing viral contamination of saliva. J Clin Periodontol. 2005;32(4):341-6.
  98. Gherlone E, Polimeni A, Fiorile F, Ghirlanda C, Iandolo R, Health T-ScotIMo. Operative Guidelines for the dental activity during phase 2 of the Covid-19 pandemic. 2020.
  99. Carrouel F, Gonçalves LS, Conte MP, Campus G, Fisher J, Fraticelli L, et al. 2020. J Dent Res. Antiviral Activity of Reagents in Mouth Rinses against SARS-CoV-2.
  100. Chaudhary P, Melkonyan A, Meethil A, Saraswat S, Hall DL, Cottle J, et al. Estimating salivary carriage of severe acute respiratory syndrome coronavirus 2 in non
    symptomatic people and efficacy of mouthrinse in reducing viral load: A randomized controlled trial. J Am Dent Assoc. 2021;152(11):903-8.
  101. Burton MJ, Clarkson JE, Goulao B, Glenny AM, McBain AJ, Schilder AG, et al. Antimicrobial mouthwashes (gargling) and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to improve patient outcomes and to protect healthcare workers treating them. Cochrane Database Syst Rev. 2020;9:CD013627.

About the Author

Miriam Ting, DMD (Temple University, magna cum laude), BDS (Singapore), Cert. Advanced Periodontology and MS (Craniofacial Biology) at USC. Diplomate, American Board of Periodontology and ICOI. Dr. Ting is founder and director, Think Dental Learning Institute and Magnifico Oral Health Foundation and practises at Think Oral Implants and Periodontics in Paoli, PA.


Jon B. Suzuki, DDS (Loyola), PhD (IIT) MBA (Pittsburgh), is the current Chairman, Food and Drug Administration, Dental Products Advisory Panel. He has Clinical Professorships at University of Maryland, University of Washington and Nova Southeastern University and was Dean, University of Pittsburgh, and Director, Graduate Periodontology and Oral Implantology, Temple University.

View more COVID-19 content as it pertains to the dental profession. 

Print this page


Have your say:

Your email address will not be published.