Chlorhexidine gluconate — the most effective antiviral mouthwash in COVID-19 pandemic

This article covers all the peer-reviewed evidence available on why chlorhexidine gluconate is the best antiviral mouthwash in our fight against SARS-CoV-2 — the COVID-19 virus.

Chlorhexidine gluconate has demonstrated antiviral activity (more than 50 years of evidence), long-lasting action inside the mouth (the only mouthwash with substantivity), and elimination of SARS-CoV-2 oropharyngeal load in hospitalized COVID-19 patients.

Early studies on the antiviral (virucidal) action of chlorhexidine:

1. The earliest experiment showing the antiviral action of Chlorhexidine comes from a study conducted way back in 1968 that recommended chlorhexidine as a virucidal disinfectant for veterinary use. These workers reported that under experimental conditions a number of viruses were sensitive to 0 05 % chlorhexidine. Under experimental lab conditions, the Herpes virus lost 5–6 log10 units of infectivity after 10 minutes’ exposure at room temperature. [1]
2. Another study conducted in 1972 showed that the infectivity titer of two strains of Herpes virus was reduced by about six log10 units by 90 minutes’ exposure to chlorhexidine at a final concentration of 0.02 % at room temperature. These experiments justify the use of chlorhexidine as a disinfectant in the medical and veterinary prophylaxis of herpetic infections. [2] Click here to read
3. Chlorhexidine gluconate completely inactivated human immunodeficiency virus (HIV) at concentrations greater than or equal to 0.2% (same as currently available mouthwashes), but Betadine did not inactivate HIV at the concentrations recommended for clinical use. [3] Click here to read
4. A study conducted in 1989 showed that chlorhexidine inhibited the replication and cytolytic activity of HSV-1 in Vero cell monolayers. When 0.2% CHX was applied topically onto the HSV-1 infected forehead skin of mice, the development of viral lesions and the viral titers in the skin and trigeminal ganglia were also moderately reduced. These data indicate that CHX oral rinse may be beneficial for the control of intraoral HSV-1 infection in certain patients, and warrants further controlled clinical study. [4] Click here to read
5. Chlorhexidine’s antiviral effect on enveloped viruses has been known since the year 1990. [5] Click here to read.

The novel coronavirus SARS-COV-2 is an enveloped virus.

Latest studies on the novel coronavirus (SARS-CoV-2)

1. Lancet’s study in April 2020 showed that chlorhexidine could inactivate SARS-COV-2 in a concentration as low as 0.05%. Currently available mouthwashes of 0.2% w/v concentration are four times stronger than 0.05%. [6] Click here to read
2. Another study (May 2020) showed that a single rinse with chlorhexidine reduced the SARS-COV-2 viral load in the mouth for 2 hours, which can help reduce the viral transmission in the pandemic. [7] Click here to read
3. An Indian study has found that chlorhexidine in 0.2% concentration inactivated SARS CoV 2 in minimal contact time, i.e., 30 secs. With a much better efficacy than povidone-iodine. [8] Click here to read
4. Taking it further, a March 2021 study states that four days of chlorhexidine use can eliminate oropharyngeal SARS-COV-2 in Covid-19 patients. [9]
   With four days of chlorhexidine use in hospitalized COVID-19 patients, 62 % of chlorhexidine mouthwash users could eliminate SARS-COV-2 from the oropharynx. In comparison, only 5.5% of people from the control group were able to achieve it.
   The number of people who eliminated the virus rose to 86 % when they also used a chlorhexidine oropharyngeal spray along with the mouthwash (vs. 6.3% control).
   Hence, if you use chlorhexidine mouthwash to rinse the mouth and gargle the throat, you will control the infection more effectively.
   The study says that chlorhexidine is a simple and safe addition to current COVID‐19 prevention guidelines and may significantly reduce disease spread. Click here to read the article

The most unique property of Chlorhexidine: Substantivity (Persistent attachment, sustained release, prolonged action) :

1. A mouthwash will significantly help, only if it binds strongly to the teeth and oral mucosal surfaces. Persistent attachment and sustained release into the mouth are critical for a prolonged antiviral action of a mouthwash inside the mouth. This property of mouthwash is known as substantivity.
2. For many decades we know that chlorhexidine is the only mouthwash to have a prolonged action inside the mouth [10](1974, Archives of Oral Biology), the only mouthwash with substantivity [11] (1999, British Dental Journal), and can be detected even 24 hours after a single rinse.[12] (2020, Archives of Oral Biology). No other mouthwash demonstrates these properties.
3. An antiviral molecule is of no use as a mouthwash if it has no persistent attachment, sustained release, and prolonged action inside the mouth. Even a good antiviral property is of no use if the mouthwash has no prolonged action, because within a few minutes after spitting, the mouth becomes refilled with new viruses entering the oral cavity from salivary glands and lungs. For decades we know that the only molecule with prolonged and sustained activity inside the mouth is chlorhexidine. [11]
4. Although we have two different concentrations of chlorhexidine — 0.12% and 0.2% available in the market, 0.2% is a better option. Substantivity was greater with 0.2% CHX than 0.12% CHX. An increase in the volume of 0.12% or 0.2% CHX mouthwash does not affect the duration of antimicrobial activity in saliva, whereas increasing the duration produces a marked increase in substantivity. [13]

Which chlorhexidine to use? The one with Anti-Discoloration System (ADS) or the one without ADS?:

1. Peer-reviewed evidence from British Dental Journal, 1999 states that commercially available chlorhexidine mouthwashes which do not produce staining are inactive usually because the active chlorhexidine molecules have been bound to another constituent of the mouthwash. [11] So for the best therapeutic effect, choose the stain-producing chlorhexidine. Click here to read
2. A new study published in October 2020 showed that chlorhexidine mouthwash without an anti-discoloration system resulted in significantly lowered plaque and gingival index compared to chlorhexidine mouthwash with an anti-discoloration following periodontal surgery. [14] Click here to read

Summary:

Chlorhexidine mouthwash has the most ideal properties — antiviral action plus substantivity- to act as an antiviral mouthwash and throat gargle against all enveloped viruses, esp. SARS-CoV-2.

We should use the old and newer lines of evidence and educate the people and help them make use of chlorhexidine mouthwash to eliminate the virus from the oropharyngeal region and reduce the transmission of the virus.

Chlorhexidine gluconate, as a mouthwash and throat gargle, has the ability to work as an effective agent in pre-exposure as well as post-exposure prophylaxis.

Chlorhexidine gluconate will be of great use in clinics to minimize the exposure of healthcare workers to the SARS-CoV-2 virus and safeguard their health.

Along with safe distancing, proper use of masks, hand sanitization, and eyewear, chlorhexidine can reduce virus transmission effectively, safeguard the doctors and clinics, offices, and households from indoor transmission.

It can also help hospitalized patients to reduce their oropharyngeal viral load effectively.

This way, chlorhexidine can help reduce infection as well as infectivity. Thus, it will help us minimize community transmission and control the pandemic crisis.

References:

[1] Eppley, J. R., Hays, M. B., and Kucera, C. J. (1968). Nolvasan: a virucide. Biochem. Rev ., 33, 9–13.

[2] Bailey A, Longson M. Virucidal activity of chlorhexidine on strains of Herpesvirus hominis, poliovirus, and adenovirus. J Clin Pathol. 1972 Jan;25(1):76–8. doi: 10.1136/jcp.25.1.76. PMID: 4335578; PMCID: PMC477227.

[3] Harbison MA, Hammer SM. Inactivation of human immunodeficiency virus by Betadine products and chlorhexidine. J Acquir Immune Defic Syndr (1988). 1989;2(1):16–20. PMID: 2465403.

[4] Park JB, Park NH. Effect of chlorhexidine on the in vitro and in vivo herpes simplex virus infection. Oral Surg Oral Med Oral Pathol. 1989 Feb;67(2):149–53. doi: 10.1016/0030–4220(89)90320–4. PMID: 2537483.

[5] Bernstein D, Schiff G, Echler G, Prince A, Feller M, Briner W. In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse. J Dent Res. 1990 Mar;69(3):874–6. doi: 10.1177/00220345900690030901. PMID: 2109001.

[6] Chin AWH, Chu JTS, Perera MRA, Hui KPY, Yen HL, Chan MCW, Peiris M, Poon LLM. Stability of SARS-CoV-2 in different environmental conditions. Lancet Microbe. 2020 May;1(1):e10. doi: 10.1016/S2666–5247(20)30003–3. Epub 2020 Apr 2. PMID: 32835322; PMCID: PMC7214863.

[7] Yoon JG, Yoon J, Song JY, Yoon SY, Lim CS, Seong H, Noh JY, Cheong HJ, Kim WJ. Clinical Significance of a High SARS-CoV-2 Viral Load in the Saliva. J Korean Med Sci. 2020 May 25;35(20):e195. doi: 10.3346/jkms.2020.35.e195. PMID: 32449329; PMCID: PMC7246183.

[8] Jain A, Grover V, Singh C, Sharma A, Das DK, Singh P, Thakur KG, Ringe RP. Chlorhexidine: An effective anticovid mouth rinse. J Indian Soc Periodontol. 2021 Jan-Feb;25(1):86–88. doi: 10.4103/jisp.jisp_824_20. Epub 2021 Jan 7. PMID: 33642749; PMCID: PMC7904017.

[9] Huang YH, Huang JT. Use of chlorhexidine to eradicate oropharyngeal SARS-CoV-2 in COVID-19 patients. J Med Virol. 2021 Mar 23. doi: 10.1002/jmv.26954. Epub ahead of print. PMID: 33755218.

[10] Bonesvoll P, Lökken P, Rölla G, Paus PN. Retention of chlorhexidine in the human oral cavity after mouth rinses. Arch Oral Biol. 1974 Mar;19(3):209–12. doi: 10.1016/0003–9969(74)90263–5. PMID: 4525807.

[11] Eley, B. Antibacterial agents in the control of supragingival plaque — a review. Br Dent J 186, 286–296 (1999). https://doi.org/10.1038/sj.bdj.4800090

[12] Reda B, Hollemeyer K, Trautmann S, Hannig M, Volmer DA. Determination of chlorhexidine retention in different oral sites using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Arch Oral Biol. 2020 Feb;110:104623. doi: 10.1016/j.archoralbio.2019.104623. Epub 2019 Nov 27. PMID: 31830639.

[13] Tomás I, Cousido MC, García-Caballero L, Rubido S, Limeres J, Diz P. Substantivity of a single chlorhexidine mouthwash on salivary flora: influence of intrinsic and extrinsic factors. J Dent. 2010 Jul;38(7):541–6. doi: 10.1016/j.jdent.2010.03.012. Epub 2010 Apr 7. PMID: 20380865.

[14] Mauland EK, Preus HR, Aass AM. Comparison of commercially available 0.2% chlorhexidine mouthwash with and without anti-discoloration system: A blinded, crossover clinical trial. J Clin Periodontol. 2020 Dec;47(12):1522–1527. doi: 10.1111/jcpe.13382. Epub 2020 Oct 28. PMID: 33020951.