Clinical use of Chlorine dioxide in the prevention of coronavirus spread through dental aerosols.

What is the current pandemic all about?

Coronavirus disease/ COVID-19/ SARS-COV2 is an infectious disease caused by a coronavirus. Infected patients show symptoms like temperature, cough, loss of smell, respiratory illness. They may do away mild symptoms without any special treatment. Patients of low immunity, aged or having a history of COPD, cardiovascular disease, diabetes cancer, are very susceptible and need immediate attention. Coronavirus spreads through infected patient’s saliva droplets and nose discharges. [1].

What is chlorine dioxide (ClO2)?

Chlorine dioxide is a yellow to reddish-yellow artificially manufactured gas. Chlorine dioxide is added to water for surface treatment and to make water fit for human consumption. When chlorine dioxide is added to water it forms chlorite ion which is also used to decontaminate water. [2] Chlorine dioxide is used in the pre-oxidation stage, wherein the ClO2 oxidizes the floating matter, bringing about coagulation, prevents the growth of algae and bacteria (biofilm). Chlorine dioxide is active as a biocide for 48 hours in the water.

Coronavirus and dental practice threat Coronaviruses is present in saliva in par with levels found in nasopharyngeal samples. One patient’s saliva also showed virus till 11th day after being hospitalized. Thus, salivary gland cells are being studied in the role of virus entry, and progress of infection. ACE2 is highly available in the epithelial lining of oral mucosa making COVID 19 infections highest in the oral mucosa.

Covid-19 spreads from one person to another. When an infected person sneezes, coughs or speaks the saliva droplets or nasal discharges get released in the air. These discharges are heavy and thus don’t travel far and settle down quickly on the ground or tables doorknobs clothes etc. [3] If a healthy individual comes across these droplets or breathe the air where the infected has sneezed or spoken, there are chances of COVID-19 to be passed on to the other. In a patient setting if a dental practitioner comes across a Covid-19 infected patient there are 100% chances of the dentist getting infected. In such a situation Dental practitioners are at great risk.

How deadly is SARS COV2 Virus?

The COVID-19 virus enters the human cells by binding to the host cell via their spike protein to angiotensin-converting enzyme 2 receptor (ACE2). Infected patients with SARS COV2 spread more viruses in their asymptomatic stage, and those in the later stages of disease shed it at a faster rate. The virus is studied to be more efficient in travelling more distance and becoming aerosolized [4].  Higher viral loads have been detected in nasal passages and the upper respiratory tract of infected people, thus when such patients talk, open their mouth, sneeze or they emit out loads of virus. Similarly, regular dental procedures like ultrasonic scaling, airotor based procedures produce various infected aerosols. This increases the chance of infecting the doctor and their fellow practitioners. Also since the virus may settle on the chair the instruments the dental tray etc. the chances of disease transmission increase to other patients as well.

A respiratory infection can be transmitted via various particles/ molecules:
1. Droplet nuclei: less than 5 mm(diameter) [11]
2. Droplet: more than 5-10mm (diameter)[11]
3. Aerosols: less than 50mm(diameter)[10]
4. Splatter: more than 50 mm [10]

Nose filters out particles above 10 microns, particles below 10 microns enter the respiratory tract and particle below 0.1 microns like the coronavirus enter the bloodstream and start targeting organs of the body. When a virus gets into the air as aerosols during sneeze cough or dental treatments they can travel a long-distance and propagate secondary infection in the environment. These aerosols remain in the air and pose a threat to healthcare workers and contaminate surfaces.

Viruses are contained in the following places for the specified duration.
• Up to 72 hours on plastic and stainless steel surfaces.
• Up to 24 hours on cardboard surfaces.
• Up to nine hours on copper surfaces.
• Up to three hours in suspended aerosols.

One study showed that ultrasonic sterilization transmits 100,000 microbes per cubic foot with 6 feet of aerosolization and that microbes can last between 35 minutes-17 hours. [5] Covering these dangers to dentists/healthcare professionals /patients; OSHA
(OCCUPATIONAL SAFETY AND HEALTH ACT) released “Guidance on Preparing Workplaces for COVID-19.

This document categorizes occupations with aerosol production as very high risk, occupation. [6]

So how can dentists minimise the virus load in their set up for the prevention of transmission of disease?

Coronavirus is known to be mostly present in the mouth and respiratory tract. Dentists can minimise the risk of viral load considerably by rinsing every patient’s mouth before they walk into the clinic and during their procedure. Chlorine dioxide can be used for the same. The EPA has set maximum concentration as 0.8mg/l for chlorine dioxide and 1.0 mg/l for chlorite ion. [7]

Japanese researches have demonstrated that gargling with drinking water reduced the incidence of upper respiratory tract infection. This very much coincided with the presence of 0.5 mg /l of chlorine which had been used to disinfect water.

The following study shows the use of chlorine dioxide in reducing virus load in aerosols.[8] A cohort of 120 patients with chronic periodontitis was pooled in for a single centre; double-blind; three group parallel designed the study. The study aimed at studying the efficacy of commercially available pre-procedural mouthwash; chlorine dioxide mouthwash, water and 0.2% CHX Gluconate. The aerosol produced by the ultrasonic unit was collected from 5 locations in the mouth. The same was then smeared on blood agar plates and incubated at 37°C for48 hours to study the growth of CFUs.

The result showed the number of CFUS to be drastically lower in patients that underwent mouth rinse with chlorine dioxide & 0.2% CHX Gluconate as compared to the water mouth rinse candidates. Also, CFUs drastically reduced in the plates with samples from the chlorine dioxide. However, their mean post-procedural CFUs were not very different.

Conclusion: Chlorine dioxide mouth rinse is found to reduce virus load significantly.

Please note in certain places chlorine dioxide is used for disinfection. Ogata found that the antimicrobial nature of chlorine dioxide is derived from its property of denaturing proteins present on virus cells. This denaturation involves the oxidation of certain amino residues majorly tryptophan and tyrosine present in the proteins. [9]

In 2012, Ogata further confirmed this theory by studying chlorine dioxide’s antimicrobial activity with respect to Influenza. The inactivation of influenza virus was brought about by denaturing of the tryptophan residues in its spike proteins. This denaturation led to the destruction of the virus’s host cell receptor binding capability. Interestingly spike protein of Covid-19 contains 54 tyrosine, 12 tryptophan and 40 cysteine residues. It’s an extremely important understanding that if these viruses come across aqueous phase of chlorine dioxide, the antimicrobial denaturing activity of the COVID 19 virus will begin, causing rapid inactivation of the virus. [9]

How does chlorine dioxide inactivate covid19 virus?

Coronaviruses have spike proteins on their surface. These spikes have host binding sites on them. When chlorine dioxide comes in contact with the virus it denatures the tyrosine tryptophan residues on the spike protein, deactivating the receptor binding and oxidises the viral genetic material.

The genetic material is made of purines and pyrimidine (guanine, cytosine adenine thymine) and the unique sequence of these make the difference. The guanine base undergoes oxidation when ClO2 comes in contact with the virus. This oxidation of guanine results in the formation of 8 oxyguanine which stops the replication of the viral nucleic acid production and thus stops the virus multiplication.

So if chlorine dioxide has a denaturing effect, how are the tissues of the human body not at risk?

Human cells have glutathione in mM concentration, in addition, they also have vitamin C & E. Together glutathione and vitamins reduce chlorine dioxide. Human cells are much bigger than bacteria or virus. So their glutathione reserve is also high. It’s said that even an isolated human cell can stay in chlorine dioxide solution for a much longer time than bacteria or virus. And as we all know the human body is made up of tissues consisting of cells. Thus we can guess the magnitude of glutathione and vitamins in the human tissues.

Also, multicellular organisms have constant transport of antioxidant and vitamins to the tissues helping them to sustain chlorine dioxide attack and recovery. Comparing the size of a bacterium/virus to a human tissue we can very well decipher that bacteria/virus needs a small amount of chlorine dioxide to be inactivated, and this small amount will be safe for human
consumption. [9]

How much time does chlorine dioxide (CIO2) take to inactivate the virus?

Viruses are smaller than bacteria. Inactivation time of virus is shorter than inactivation time of bacteria under the same conditions of CIO2 strength, temperature etc. The following arguments support this assumption:

The diameter of COVID 19 virus is 120nm
1. Viruses are smaller than bacteria, so the diffusion-controlled reaction with CIO2 would be faster in the virus.
2. CIO2 need not penetrate the virus to inactivate it; it can merely react with a few tyrosine tryptophan bases in the protein to denature the host binding sites.
3. Viruses don’t have glutathione or similar protective metabolic molecules to protect themselves from CIO2 attack. (Viruses have no metabolic activity)

These points lead to the fact that after contact is made between virus and chlorine dioxide inactivation is quick. However, for a virus in aqueous phases like nasal discharge or fluid droplet or epithelial lining of mucous membranes, the diffusion of chlorine dioxide in the water is a rate-limiting step. The time required to inactivate the virus is shorter as compared to the time required for the CIO2 to be transported to the virus.[9]

An on-going study (expected to be completed in June) is reviewing the efficacy of oral chlorine dioxide in the treatment of COVID 19 patients. https://clinicaltrials.gov/ct2/show/study/NCT04343742

What makes us hypothesize that Chlorine dioxide will be useful in reducing transmissions in clinical settings?

Dilution: EPA has approved a concentration of 0.8 mg/l of chlorine dioxide in drinking water [7]. However this water isn't going to be ingested, so we can safely hypothesize the use of a higher concentration for reducing viral load spread through aerosols.

Chlorine dioxide’s long history in the use as a disinfectant. Its use in drinking water treatment gives confidence that it can be edible at specified concentrations. It would also be safe to increase the concentration of ClO2 in water, this will significantly
reduce the viral load while working with dental handpieces as the patient is not going to ingest it. Using a rubber dam along with chlorine dioxide will reduce the chances of transmission to the dental operator and also reduce the virus in aerosols. Proved efficacy against SARS coronavirus family of virus. It’s easy to use, so we can consider its use in high-speed handpieces as an irrigant, this
will inactivate the virus in saliva and in aerosols. This will not affect the dental instruments like other irrigants.

Chlorine dioxide is not pungent at a very small quantity that may be used for irrigation in dental setups. It is economical to use.

PLEASE TAKE NOTE THAT THIS CHLORINE DIOXIDE WATER IN ADDITION TO OTHER SAFETY PROCEDURES WILL SIGNIFICANTLY REDUCE VIRAL LOAD.

References:

1. WHO. 2020. CORONAVIRUS. [ONLINE] Available at: https://www.who.int/health-
topics/coronavirus#tab=tab_1. [Accessed 18 May 2020].

2. National Center for Biotechnology Information. PubChem Database. Chlorine dioxide, CID=24870, https://pubchem.ncbi.nlm.nih.gov/compound/Chlorine-dioxide [accessed on May 18, 2020]

3. WHO. 2020. Q&A on coronaviruses (COVID-19). [ONLINE] [Accessed 18 May 2020].

4. Perio implant advisory. 2020. COVID-19 and the problem with dental aerosols. [ONLINE] Available at: https://www.perioimplantadvisory.com/periodontics/oral-medicine-anesthetics-
and-oral-systemic-connection/article/14173521/covid19-and-the-problem-with-dental-aerosols. Accessed 19 May 2020.

5. Miller RL. Characteristics of blood-containing aerosols generated by common powered dental instruments. Am Ind Hyg Assoc J. 1995;56(7):670-676. doi:10.1080/15428119591016683

6 Guidance on preparing workplaces for COVID-19. US Department of Labor. Occupational Safety and Health Administration. 2020. https://www.osha.gov/Publications/OSHA3990.pdf

7 AGENCY FOR TOXIC SUBSTANCES AND DISEASE REGISTRY. 2020. Public Health
Statement for Chlorine Dioxide and Chlorite. [ONLINE] Available at:
https://www.atsdr.cdc.gov/phs/phs.asp?id=580&tid=108. [Accessed 19 May 2020].

8 Saini R. Efficacy of a preprocedural mouth rinse containing chlorine dioxide in the reduction of viable bacterial count in dental aerosols during ultrasonic scaling: A double-blind, placebo-controlled clinical trial. Dent Hypotheses 2015;6:65-71

9. Kály-Kullai, K & Wittmann, Maria & Noszticzius, Z & Rosivall, Laszlo. (2020). Can
chlorine dioxide prevent the spreading of coronavirus or other viral infections? Medical
hypotheses. Physiology international. 1-11. 10.1556/2060.2020.00015.

10. Harrel SK, Molinari J. Aerosols and splatter in dentistry: a brief review of the literature and
infection control implications. J Am Dent Assoc. 2004;135(4):429‐437.
doi:10.14219/jada.archive.2004.0207

11 WHO. 2020. Modes of transmission of the virus causing COVID-19: implications for IPC precaution recommendations. [ONLINE] Available at https://www.who.int/news-room/commentaries/detail/modes-of-transmission-of-virus-causing-covid-19-implicationsfor-ipc-precaution-recommendations. [Accessed 22 May 2020].

Authors: 
Dr Anuj H. Gandhi
BDS. (M.G.V. Dental College, Nashik)
Basic Implantology (Bapuji Dental College, Davangere.)
F.I.C.O.I, U.S.A.
Clinical Mastership in Oral Implantology from StonyBrook University.
One Year Online Externship Program, Dental XP, Atlanta, USA
KOL - BioHorizons
KOL - Dentium

Malvika A. Gandhi
Btech in Biotechnology (DY Patil University)
MBA Marketing (Cardiff University, UK)
3 years of work experience with Lupin pharmaceutical company
(management - licensing) for the India market and CIS Market.

Tags: