What do COVID-19 and SARS-CoV-2 have to do with oral health?

As an oral health foundation, we show you the scientific connections between oral health, the oral immune system and their role in the fight against COVID-19. Is this all too complicated for you and would you like it to be simpler? Then take a look at the press section or send an email to info@mundgesundheitsstiftung.de

The oral cavity as a hotspot and first line of defense against SARS-CoV-19
A recent Chinese study shows that the oral cavity is the most important gateway for the SARS-CoV-19 virus. This is because the virus enters the body via so-called ACE2 receptors. Xu et al. found the highest receptor load in the oral cavity, particularly on the tongue. The oral cavity is therefore the hotspot for viral infection with the virus and not the lung tissue, as previously assumed.

A healthy oral mucosa and an intact immune system in the oral cavity are the body's first line of defense against the invasion of the virus. "Preliminarily, these results have explained the basic mechanism that the oral cavity is a potentially high risk site for SARS-CoV-19 infection susceptibility and provided evidence for the importance of future prevention strategies in dental clinical practice as well as in daily life. (1)

aMMP-8: A simple test checks the immune fitness and barrier function of the oral cavity
The enzyme activated matrix metalloproteinase-8 (aMMP-8) shows how healthy the mucosa is and whether it is fulfilling its barrier function. This test provides information on whether and to what extent collagen degradation is taking place in the oral cavity or inflammatory processes are at work. Elevated aMMP-8 levels are an indication of an activated immune system (silent inflammation) and, as a result, a disturbed barrier of the oral mucosa due to the breakdown of the collagen structures of aMMP-8. A simple mouthwash test for aMMP-8 provides information about the immune fitness and functionality of the oral barrier in five minutes. (2)

Pathogenic oral germs lead to dreaded secondary infections of the respiratory tract
Chinese data also shows that 50% of patients who had to be admitted to hospital had a secondary infection caused by bacteria. In the worst case, this leads to sepsis and death from organ failure. All patients who developed sepsis died in hospital. (3)

In this context, it is interesting to note that Italian researchers found pathogenic bacteria from the oral cavity in the bronchial secretions of patients back in 2015. In patients whose bronchi were colonized with Treponema denticula, the aMMP-8 values were significantly increased. (4) This means that periodontal germs from the oral cavity can colonize the lower respiratory tract and lead to a secondary bacterial infection. This can potentially trigger pneumonia or even sepsis. The study was carried out using the PerioSafe saliva test. It shows how important the aMMP-8 value is. Intensive oral hygiene can significantly reduce the number of pathogenic germs in the oral cavity, which can reduce or even prevent colonization of the lower respiratory tract.

Periodontitis is the most common infectious disease - young people also affected
Against the backdrop of the COVID-19 pandemic, this fact is particularly important. Globally, between 20 and 50 percent of the population suffer from periodontitis - often without realizing it. (6) In Germany alone, this affects more than 11.5 million people. Advanced periodontitis with a pocket depth of more than 6 mm affects 10 to 15 percent of the world's population (7). The World Health Organization even calls it the most common infectious disease worldwide. Using the aMMP-8 test, a Finnish study was able to show that periodontitis is not only an issue in the adult population, but also plays a role in adolescents. (8) This is interesting in light of the increasingly younger COVID-19 patients with fatal outcomes.

Periodontitis and diabetes - risk group for COVID-19
Periodontitis and diabetes are common, complex, chronic diseases with an established bidirectional relationship. In particular, patients with diabetes have a higher prevalence and severity of periodontitis. The worse the glycemic control, the more pronounced the severity. (9) Italian data show that the mortality rate of COVID-19 patients who also suffered from diabetes is much higher than average at 15%. This may be related to more frequent and more severe periodontitis.

A recent Greek study found that 27.5% of all dental patients had previously unknown hyperglycemia - aMMP-8 levels were significantly elevated in these patients. The authors of the study concluded that aMMP-8 is suitable as a screening test for previously undiagnosed diabetes. (10)

Periodontitis and cardiovascular disease - risk group for COVID -19
However, not only COVID-19 patients with diabetes as a comorbidity have a significantly higher mortality rate, but also patients with cardiovascular disease. Numerous studies have shown a link between chronic cardiovascular disease and peridontitis. What both diseases have in common is that they are silent inflammations. In their review article, Alfakry et al. show a connection between increased aMMP-8 levels in saliva in patients with chronic heart disease and existing periodontitis. (11)

Periodontitis and systemic diseases
An imbalance between healthy and pathogenic pathogens in the oral cavity is closely associated with numerous systemic diseases, lung infections, cardiovascular diseases, rheumatoid arthritis, diabetes, Alzheimer's disease, infertility and complications during pregnancy. (5) Patients with diabetes and heart disease in particular have a greatly increased risk of complications and even death if infected with SARS-CoV-19.

High mortality in young patients with COVID-19
Finnish researchers write that elderly patients and patients with pre-existing chronic conditions are most affected by severe complications and deaths in the COVID-19 pandemic. This fact has been well communicated in the media and has created a sense of security for people who believe they do not fall into one of these risk categories. However, the fact is that not everyone is as safe from this disease as they think. In Italy, over 50% of confirmed COVID-19 cases required hospitalization and the mortality rate was over 6%. 12% of Italian ICU patients are between 18 and 50 years old. It is possible that the occurrence of periodontitis already in adolescents and the associated burden on the immune system due to silent inflammation, a permeable mucosa and unrecognized comorbidities play a role. In all these cases, the aMMP-8 test shows the state of the immune system and whether individual preventive measures are advisable.

Immune fitness counts in the fight against SARS-CoV-19
There is currently no vaccine or active substance against SARS-CoV-19 in sight. So if an infection with the disease is unavoidable, the immune system is vital for survival. The better this "immune fitness" is, the better the body fights diseases - including COVID-19.

The simple aMMP-8 saliva test has shown in numerous studies that it not only plays a central role in oral diseases of the periodontium. It is also significantly elevated in systemic concomitant diseases such as diabetes mellitus, chronic heart disease and rheumatoid arthritis. The PerioSafe aMMP-8 mouth rinse test therefore offers a simple, inexpensive and quick way to test immune fitness.

If the immune system is under attack, it releases the enzyme matrix metalloproteinase-8 (aMMP-8) as part of inflammatory reactions. If the value is high, the immune system is under attack; if the value is low, the immune system is fit.

We know that in many diseases, it is not the pathogen itself but the body's inflammatory response to the pathogen that damages the body. COVID-19 is no different. 50% of hospitalized COVID-19 patients who die had a secondary infection.

If we want to reduce the risk of serious complications from COVID-19, we need to improve our immune fitness and reduce the level of inflammation in the body as much as possible.

The simple mouth rinse test (dentognostics, Germany) for aMMP-8 identifies oral inflammation in just five minutes. This is important for two reasons. Firstly, oral inflammation contributes to the overall inflammatory burden of the body and the source of inflammation in the oral cavity should be controlled with appropriate measures. Inflammation in the mouth is usually stimulated by oral bacteria.

Individual prevention strategies for COVID-19
A new Chinese study shows that the SARS-CoV-19 virus can be detected in large quantities in the nasopharynx and throat in the very early phase of the disease. After the onset of symptoms, the number of viruses in this area decreases rapidly. This means that isolating sick patients has little chance of success in containing this pandemic. This is because people with few or just beginning symptoms are the greatest source of infection. (13) This is in line with the observations of Prof. Drosten (virologist, Charité). Therefore, the global strategy is to isolate healthy people in order to keep transmission as low as possible. However, this also shows how important individual precautions (prevention) are to avoid contracting Covid-19.

A look at history helps - measures for the Spanish flu
The largest global pandemic to date was the Spanish flu, which killed between 50 and 100 million people in the years 1918-1919.

The measures taken back then to protect and heal people still seem relevant today:

To prevent infection, doctors and nurses wore gloves, gowns and head coverings. After contact with patients, they had to wash their hands thoroughly with disinfectant before eating, and the use of common drinking cups, towels and other objects was strictly forbidden. The patients' dishes and utensils were kept separately and placed in boiling water after each use.

Patients with secondary bacterial infections, such as pneumonia and meningitis, used paper plates, drinking cups and napkins.

Oral hygiene was particularly important! Mouthwash and gargling were used extensively, twice a day a antimicrobial silver ointment applied to the nasal mucous membranes to prevent infection of the ears.

Equally important were healthy meals (vitamins, minerals), warmth, fresh air and, above all, sunlight (vitamin D).

The success: Of the medical staff at the Camp Brooks camp (154 people), only six nurses and two caregivers developed influenza.

Antimicrobial properties of silver
The antimicrobial properties of silver were already being used in ancient times to preserve food and water supplies. Back then, people did not know what is now scientifically proven: silver ions inhibit the growth of bacteria. However, these properties were forgotten with the discovery of antibiotics. It was only against the background of the development of resistance that scientists rediscovered the antibacterial properties of silver ions, e.g. as a sterile wound dressing for plasters.

The antimicrobial activity of silver is based on three mechanisms:

1. Silver ions make the bacterial envelope permeable and destroy it,
2. When silver ions enter the interior of the bacteria, they hinder cell respiration and metabolism,
3. Silver ions prevent the reproduction of genetic material (DNA); cell division cannot take place.

Countless microorganisms live in our mouths. Food and air also constantly transport additional pathogens into our oral cavity. After normal tooth brushing and mouth rinsing, the remaining plaque causes local inflammation.
Especially now during the corona pandemic, it is a top priority to take good care of the oral mucosa. The fewer harmful germs there are in the mouth, the better. Especially with regard to secondary infections such as pneumonia and sepsis.

Not all silver is the same
Nowadays, nanosilver is often used in cosmetics and other personal care products. Silver colloids (colloidal silver) can also be described as nanosilver. However, consumer advocates and the Federal Ministry of Health criticize the fact that toxic silver ions are continuously released from them. These can lead to stomach and liver damage as well as neurological damage and accumulate in the brain and the rest of the body.

Larger particles are called micro-silver. MicroSilver BG™, for example, is manufactured in a specially developed production facility. Only high-purity elemental silver is used for its production and no silver-containing ionic compounds are created. MicroSilver BG™ is contained in PerioSafe® dental care products (toothpaste and mouthwash), for example.

A clinical study was able to prove that these pure silver ions from PerioSafe® toothpaste with MicroSilver BG™ adhere to the harmful bacteria in the oral cavity for up to 12 hours and prevent them from multiplying. This reliably reduces plaque, bleeding of the oral mucosa and bad breath with regular use (study by Prof. Frankenberger, University of Erlangen).

Contain harmful bacteria and reduce bleeding: This effectively combats low-threshold inflammation (silent inflammation) and thus strengthens the entire immune system.

The advantage of oral care products with microsilver:

• Do not irritate the oral mucosa - unlike mouth rinses containing chlorhexidine
• Are well suited for long-term use - chlorhexidine should not be used over a long period of time
• The silver ions contained adhere to the plaque for up to twelve hours and reduce its growth

Individual prevention - everyone is in demand
Since an infection with SARS-CoV-19 viruses cannot be ruled out or is even likely despite the best hygiene measures, everyone should strengthen their individual immune fitness.

First and foremost, this includes knowledge of the oral immune defense, which can be determined within 5 minutes using an aMMP-8 self-test. If the values are elevated, this is primarily a sign of colonization of the oral cavity with harmful germs.

Measures to eliminate these bacteria reduce the inflammation. Suitable measures include more frequent professional dental cleanings at the dental practice. However, in the current COVID-19 outbreak areas where social distancing is recommended, measures can be taken to improve oral hygiene at home. These include brushing properly for two minutes twice a day, cleaning with interdental brushes and using bacteria-inhibiting toothpastes and mouthwashes.

The second reason why it is important to identify oral inflammation is that it indicates the immune fitness of the whole body. We know that oral inflammation (often associated with gum disease) becomes more common with age and is more prevalent in patients with chronic diseases such as diabetes and cardiovascular disease. The increased immune activity that can be measured with aMMP-8 in the mouth is a sign of poor immune fitness.

Other individual preventive measures include

• aMMP8 Measurement of the oral immune system (twice a year)
• Brush your teeth regularly (two to three times a day)
• Daily cleaning of the interdental spaces (interdental brushes, dental floss)
• Regular use of suitable antimicrobial mouth rinses
• Varied, fresh and vitamin-rich diet
• Intake of vitamin C and vitamin D

1. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Xu, Hao & Zhong, Liang & Deng, Jiaxin & Peng, Jiakuan & Hongxia, Dan & Zeng, Xin & Li, Taiwen & Chen, Qianming. (2020). International Journal of Oral Science. 12
2. Matrix metalloproteinase-8 levels in oral samples as a biomarker for periodontitis in the Chinese population: an observational study. Chao Yuan, Xiaochen Liu, and Shuguo Zheng. BMC Oral Health. 2018; 18: 51. doi: 10.1186/s12903-018-0512-8
3. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Fei Zhou, Ting Yu, Ronghui Du, Guohui Fan, Ying Liu, Zhibo Liu, et al.; Published:March 11, 2020DOI:https://doi.org/10.1016/S0140-6736(20)30566-3
4. Elevated Matrix Metalloproteinase Levels in Bronchi Infected with Periodontopathogenic Bacteria. Luca Bernasconi, Liza L. Ramenzoni, Ahmed Al-Majid, Gabrielo M. Tini, Sereina M. Graber, Patrick R. Schmidlin, and Sarosh Irani. PLoS One. 2015; 10(12): e0144461. doi: 10.1371/journal.pone.0144461
5. From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease. Purnima S. Kumar. J Physiol 595.2 (2017) pp 465–476
6. European workshop in periodontal health and cardiovascular disease-scientific evidence on the association between periodontal and cardiovascular diseases: A review of the literature. Sanz M, D’Aiuto F, Deanfield J, Fernandez-Avilés F. Eur Heart J Suppl 2010;12 Suppl B:B3-12.
7. Review: Strengthening the Prevention of Periodontal Disease: The WHO Approach. Poul Erik Petersen and Hiroshi Ogawa. J Periodontol (12/2005)
8. Active Matrix Metalloproteinase-8 Point-of-Care (PoC)/Chairside Mouthrinse Test vs. Bleeding on Probing in Diagnosing Subclinical Periodontitis in Adolescents. Ismo T. Räisänen , Timo Sorsa, Gerrit-Jan van der Schoor, Taina Tervahartiala, Peter van der Schoor, Dirk-Rolf Gieselmann and Anna Maria Heikkinen. Diagnostics 2019, 9, 34; doi:10.3390/diagnostics9010034
9. Diabetes and periodontal disease: a two-way relationship. L. Casanova, F. J. Hughes and P. M. Preshaw. British Dental Journal 2014; 217: 433-437. DOI: 10.1038/sj.bdj.2014.907
10. Prediabetes/Diabetes Can Be Screened at the Dental Office by a Low-Cost and Fast Chair-Side/Point-of-Care aMMP-8 Immunotest; Andreas Grigoriadis, Timo Sorsa, Ismo Räisänen, Pirjo Pärnänen, Taina Tervahartiala, and Dimitra Sakellari; Diagnostics 2019, 9, 151; doi:10.3390/diagnostics9040151
11. Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease. Hatem Alfakry, Ernst Malle, Chintan N Koyani, Pirkko J Pussinen, Timo Sorsa. Innate Immunity 2015; 22:1. https://doi.org/10.1177/1753425915617521
12. COVID-19: Preparing for the Inevitable. Sorsa T., Nwhator S.O., Sakellari D., Grigoriadis A., Pfützner A., Kleine-Gunk B., and Räisänen, I.T. 2020 submitted
13. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. Lirong Zou et al. N EngJ Med 382;12