|Year : 2020 | Volume
| Issue : 2 | Page : 74-78
Povidone-iodine: “The first line of defense” with potential anti-severe acute respiratory syndrome coronavirus-2 efficacy
Nishant Negi1, Vinay Kumar Bhardwaj2, Deepak Sharma3, Rajiv Sharma1, Toufiq Asad1, Abdul Shamal1
1 Department of Orthodontics and Dentofacial Orthopaedics, H.P. Government Dental College and Hospital, Shimla, Himachal Pradesh, India
2 Department of Public Health Dentistry, H.P. Government Dental College and Hospital, Shimla, Himachal Pradesh, India
3 Department of Periodontology, H.P. Government Dental College and Hospital, Shimla, Himachal Pradesh, India
|Date of Submission||04-Jul-2020|
|Date of Acceptance||16-Oct-2020|
|Date of Web Publication||16-Feb-2021|
Dr. Deepak Sharma
Department of Periodontology, H.P. Government. Dental College and Hospital, Shimla - 171 001, Himachal Pradesh
Source of Support: None, Conflict of Interest: None
An outbreak of new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) (coronavirus disease-19), has assumed the proportion of global pandemic having affected more than 200 countries and territories. In the absence of any specific treatment, efficient disinfectant and antiseptic products are useful to help prevent the spread of infection. Povidone-iodine formulations are well known for their broad-spectrum antimicrobial action and a remarkable safety profile. They have shown in vitro virucidal activity against different coronaviruses. Till the time there is a concrete clinical evidence of efficacy of antiseptic agents against the current coronavirus, povidone-iodine formulations can be used widely as first choice antiseptics as well as for preventive and prophylactic management of SARS-CoV2 infection. This review highlights the importance of Povidone-Iodine formulations in health-care settings as broad-spectrum antiseptic, especially because of their potential virucidal activity against SARS-CoV2.
Keywords: Coronavirus, coronavirus disease, povidone-iodine, severe acute respiratory syndrome coronavirus 2
|How to cite this article:|
Negi N, Bhardwaj VK, Sharma D, Sharma R, Asad T, Shamal A. Povidone-iodine: “The first line of defense” with potential anti-severe acute respiratory syndrome coronavirus-2 efficacy. Int J Oral Health Sci 2020;10:74-8
|How to cite this URL:|
Negi N, Bhardwaj VK, Sharma D, Sharma R, Asad T, Shamal A. Povidone-iodine: “The first line of defense” with potential anti-severe acute respiratory syndrome coronavirus-2 efficacy. Int J Oral Health Sci [serial online] 2020 [cited 2022 Aug 9];10:74-8. Available from: https://www.ijohsjournal.org/text.asp?2020/10/2/74/309447
| Introduction|| |
The novel coronavirus disease-19 (COVID-19) caused by the 2019 novel coronavirus is an urgent threat to the world. It was first detected during an unexplained cluster of pneumonia cases in Wuhan, China, in December 2019 and has since been declared a pandemic by the World Health Organization. As of June 21, 2020, this disease has been reported in more than 180 countries with more than 8,708,008 cases and 461,715 deaths. This enveloped, single-stranded RNA virus has been renamed severe acute respiratory syndrome coronavirus-2 (SARS-COV2) as it is similar to the coronavirus responsible for SARS-COV, a member of subgenus sarbecovirus (beta-CoV lineage B), with which it shares more than 79% of its sequence, but it is more distant to the coronavirus responsible for Middle East respiratory syndrome (MERS), a member of the merbecovirus subgenus (only 50% homology with SARS-COV2).
Dental care settings are at a high risk of 2019-n CoV infection as they involve face-to-face communication with the patients. The pathogenic microorganisms can be transmitted in dental settings through inhalation of airborne microorganisms, direct contact with blood, oral fluids, or other patient materials, contact of conjunctival, nasal, or oral mucosa with droplets and aerosols containing microorganisms generated from an infected individual and indirect contact with contaminated instruments and/or environmental surfaces.,,
Therefore, it is of utmost importance to maintain strict infection control practices in dental care settings. Among different infection control practices, antiseptics have an important role in controlling the spread of nosocomial infections including COVID infection. Povidone-iodine formulations have been most recommended for infection control in hospital care settings. Currently, these formulations have specifically been advocated for their anti-coronavirus activity., This review highlights the importance of povidone-iodine formulations in health-care settings as broad-spectrum antiseptic, especially because of their potential virucidal activity against SARS-CoV2.
| Povidone-Iodine Background|| |
Povidone-iodine (iodine with the water-soluble polymer polyvinylpyrrolidone, PVP-I) was discovered in 1955 at the industrial toxicology laboratories in Philadelphia by Shelanski and Shelanski. It consists of a complex of povidone hydrogen iodide and elemental iodine. It was developed to find an antimicrobial iodine complex that was less toxic than tincture of Iodine, which causes burns. It is listed on the WHO, list of essential medicines, a list of most important medicines necessary for any functional health-care system. PVP-I is also available over the counter and is often used as a broad-spectrum topical antiseptic, mouthwash, nasal spray, etc., The formulations are typically manufactured with concentrations of 7.5%–10% PVP-I in solution, with oral formulations including 1% gargle, in addition to surgical scrubs, ointments, and scrubs.
| Mechanism of Action|| |
The antimicrobial action of PVP-I occurs after free iodine (I2) dissociates from the polymer complex. It is the free iodine that mediates the basic mechanism of action which involves disruption of microbial metabolic pathways as well as destabilization of the structural components of cell membranes, causing irreversible damage to the pathogen. An equilibrium is achieved in such circumstances, with more PVP-bound iodine released into solution to replace the iodine that is consumed by germicidal activity. The maintenance of this equilibrium ensures long-lasting efficacy during bouts of microorganism proliferation, as well as better tolerability for patients due to lower levels of irritation. The concentration of free iodine is the determining factor of the antimicrobial activity of PVP-I., PVP-I exposure leads to destruction of cytosolic and nuclear structures in bacteria and damage to cell wall in fungi., In addition to a direct killing action on bacteria, PVP-I also inhibits the release of pathogenic factors such as exotoxins, endotoxins, and tissue-destroying enzymes. Furthermore, iodine is a scavenger of free radical oxygen species, contributing to anti-inflammatory properties.
PVP-I elicits potent antiviral activity by blocking viral attachment to the host cell receptors and inhibition of viral release from infected cells. PVP-I inactivates the essential viral enzymes, thereby blocking the viral release from the host cells, preventing further spread of the virus to the host cell receptor. In addition, PVP-I also inhibits viral hemagglutinin, resulting in the blockade of attachment to the host cell receptor.
The lack of reported resistance to PVP-I to date is thought to be due to the sheer diversity of susceptible targets within each pathogen, an important aspect to be considered in the face of rising resistance and mutations. In addition to a broad-spectrum effect, PVP-I has also demonstrated hemostyptic, anti-inflammatory, and healing effects.,
| Antimicrobial Spectrum|| |
The oral cavity and throat of healthy individuals are known to be inhabited by hundreds of diverse bacteria, fungi, protozoa, and viruses that colonize different surfaces of the oral and oropharyngeal cavities., They also act as a reservoir of highly pathogenic microorganisms. This indicates the need for antiseptic agents with broad-spectrum activity, as well as oral formulations that ensure whole oral and oropharyngeal antiseptic coverage. Numerous studies have shown that PVP-I has a broader antimicrobial spectrum than other available antiseptics including chloroxylenol, chlorhexidine, polyhexanide, hexetidine, and quaternary ammonium compounds showing efficacy against Gram-positive and Gram-negative bacteria, bacterial spores, fungi, protozoa, and several viruses., Although alcohol-based antiseptics also have broad potency, unlike PVP-I formulations, they typically have no effect on fungal or bacterial spores.
| Antiviral Spectrum|| |
Povidone-iodine has been reported as having highest virucidal activity profile among several antiseptics such as chlorhexidine, benzalkonium chloride, Benzethonium Chloride (BEC) and alkyl-diaminoethyl-glycine hydrochloride. Kawana et al. in their in vitro studies found that PVP-I gargle effectively inactivated a panel of viruses that included both enveloped and nonenveloped viruses such as adenovirus, mumps, rotavirus, poliovirus (type 1 and 3), coxsackievirus, rhinovirus, herpes simplex virus, rubella, measles, influenza, and human immunodeficiency virus. PVP-I gargles have also demonstrated rapid virucidal activity against swine influenza viruses (H1N1, H3N2, H1N2, H5N3, H7N7, and H9N2).,
| Anti-Coronavirus Activity|| |
PVP-I formulations have been shown to be active in vitro against coronaviruses that have caused epidemics in the past two decades, namely SARS-COV causing the SARS epidemic of 2002–2003 and MERS-COV the agent responsible for causing the MERS epidemic of 2012–2013 [Table 1]. Kariwa and Fujii showed that the treatment in vitro of SARS-COV with various preparations of PVP-I for 2 min was enough to reduce the viral activity to undetectable levels.
Eggers et al. evaluated different formulations of PVP-I for antiviral activity against the MERS coronavirus and found that the viral titer could be reduced by a factor of C4log 10, corresponding to ≥99.99% inactivation levels. This remarkable level of potency was achieved within 15 s of application of each PVP-I formulations which included a 7.5% surgical scrub, a 1% PVP-I gargle/mouthwash, and 4% PVP-I skin cleanser formulations. They further recommended that the PVP-I-based hand hygiene products can be used to decontaminate virally infected skin, while PVP-I mouthwash can reduce viral load in the oral cavity and the oropharynx, potentially aiding in the support of hygiene measures needed to reduce the severity of future MERS outbreak. In a subsequent study, Eggers et al. used 7% PVP-I diluted to. 23% as a mouthwash/gargle to reduce the viral titers of both MERS and SARS-CoV by ≥99.99% within 15 s of application. SARS-COV2 is highly homologous with SARS-COV, and as such it is considered a close relative of SARS-COV. It is believed that it may behave similarly to SARS-COV with regard to susceptibility against PVP-I formulations.
| Safety and Tolerance|| |
PVP-I is well tolerated by majority of the patients. Allergenic dermatitis and significant toxicity after prolonged skin contact with PVP-I have been reported to be rare complications., Gargled PVP-I is well tolerated when compared with other gargled antiseptics. The use of PVP-I mouthwash for four times daily for a short period (2 weeks) or once daily for a prolonged period (24 weeks) was not found to affect thyroid function., However, increased serum thyroid-stimulating hormone concentrations may occur after prolonged use. PVP-I is therefore not to be used in those with hyperthyroidism and other diseases of thyroid. Short-term use of PVP-I has not been shown to irritate healthy or diseased oral mucosa or exhibit adverse effects, such as discoloration of teeth and tongue and change in taste. PVP-I products should be used during pregnancy and lactation with caution. PVP-I was found to be favorably tolerated by children receiving PVP-I for dental conditions.
| Clinical Applications|| |
PVP-I formulations enjoy widespread use in hospitals as antiseptic and disinfectant due to their broad-spectrum anti-infective profile, low potential for resistance as well as hemostatic and anti-inflammatory properties. PVP-I is available in different strengths and formulations, as a 10%, 7.5% and 1% PVP-I gargle and mouthwash and 0.45% throat spray, thereby allowing flexibility in design regimens to suit individual patient needs. Some of its common uses include antiseptic treatment of skin and mucous membranes in surgical procedures, management of burns and wounds, and disinfection of medical equipment such as catgut catheter, knife blades, ampules, plastic items, rubber goods, brushes, thermometers, and vials.
PVP-I formulations are also widely used during oral and maxillofacial surgical procedures. The use of PVP-I as a prophylactic mouthrinse to reduce postoperative bacteremia after periodontal and maxillofacial surgical procedures has also been demonstrated. A preprocedural rinse of PVP-I was shown to reduce the level of microorganisms generated in aerosol and spatter during dental procedure with rotary instruments. PVP-I mouthrinse has been used in management of gingivitis and periodontitis. PVP-I has also been found to be effective in the prevention of dental caries in high-risk children.
Gargling and rinsing with 10–15 ml undiluted PVP-I followed up for a minimum of 30 s has been used for the treatment and prevention of sore throats. Given the potential of PVP-I in reducing the incidence of airborne or droplet transmitted respiratory infections (e.g., SARS, avian flu, and swine flu), Kanagalingam et al. recommended undiluted PVP-I to be used as a protective measure by rinsing the mouth for 2 min up to four times a day. Gargling has been strongly recommended for both prevention and treatment of URTIs in Japan, a practice supported by finding from studies that looked at the role of gargling in both healthy individuals and those with frequent or persistent respiratory infections.,, Japanese clinical respiratory guidelines recommend gargling with PVP-I (four times a day) in both inpatient and health-care workers, for the prevention of hospital-acquired pneumonia. PVP-I has also been recommended as a preventive measure against pandemic influenza.
| Role of Povidone-Iodine Formulations During Current Pandemic|| |
Although clinical evidence regarding the efficacy of PVP-I formulations against SARS-COV2 is unavailable at the moment, the success of these formulations against related coronaviruses in in vitro studies has given some confidence regarding their use during current pandemic. Based on these in vitro studies, numerous authors have advocated wider and aggressive usage of PVP-I formulations during current pandemic.,,,
Kirk-Bayley et al. have proposed that a 0.5% (5 mg/ml) PVP-I solution be applied to the oral, oropharyngeal, and nasopharyngeal mucosa of all patients having procedures (including examination) in or around the mouth and nose or procedures that transit those areas and the health-care professionals carrying out those procedures which include dentistry and oral surgery, ENT-ORT examination and treatment, endotracheal intubation, endoscopy, and bronchoscopy. This application is advocated in the form of 0.3 ml nasal spray of 0.5% PVP-I per nostril followed by 9 ml mouthrinse of 0.5% PVP-I for 1 min. For unconscious patients, they advocated an oral care sponge swab soaked in 2 ml of 0.5% PVP-I and wiped around all oral mucosal surfaces. This protocol has to be repeated every 2–3 h for a maximum of four times by health-care workers if multiple patients are to be attended. Farzan and Firoozi have also recommended the preprocedural PVP-I mouthrinse against SARS-COV2. Lubomirov and Petkanchin recommend frequent PVP-I rinsing, gargling, and spraying (or applying a palm in the nose) for health-care professionals and also for general population as a preventive and prophylactic tool. Based on the available evidence, we also recommend that PVP-I formulations should be widely used as antiseptic against SARS-CoV2. There is an urgent need for clinical trials of antiseptics against this disease.
| Conclusion|| |
PVP-I products offers a great potential in prevention of COVID in patients, health-care workers, and general population. Based on the available evidence, PVP-I products should be the first choice antiseptic in dentistry and other health-care settings. The role of PVP-I oral, nasal, and throat hygiene products as an emergency mass preventive therapy should be urgently explored.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al
. Genomic characterization and epidemiology of 2019 novel coronavirus: Implication for virus origins and receptor binding. Lancet 2020;395:565.
Harrel SK, Molinari J. Aerosols and splatter in dentistry: A brief review of the literature and infection control implications. J Am Dent Assoc 2004;135:429-37.
Cleveland JL, Gray SK, Harte JA, Robison VA, Moorman AC, Gooch BF. Transmission of blood-borne pathogens in US dental health care settings: 2016 update. J Am Dent Assoc 2016;147:729-38.
Wei J, Li Y. Airborne spread of infectious agents in the indoor environment. Am J Infect Control 2016;44:S102-8.
Eggers M. Infectious disease management and control with Povidone Iodine. Infec Dis Ther 2019;8:581-93.
Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci 2020;12:9.
Eggers M, Eickmann M, Zorn J. Rapid and effective virucidal activity of povidone-iodine products against Middle East respiratory syndrome coronavirus (MERS-CoV) and modified Vaccinia virus Ankara (MVA). Infect Dis Ther 2015;4:491-501.
Kirk-Bayley J, Challacombe S, Sunkaraneni VS, Combes J. The Use of Povidone Iodine Nasal Spray and Mouthwash During the Current COVID-19 Pandemic May Reduce Cross Infection and Protect Healthcare Workers; 2020.
Rackur H. New aspects of mechanism of action of povidone-iodine. J Hosp Infect 1985;6 Suppl A: 13-23.
Shirai J, Kanno T, Tsuchiya Y, Mitsubayashi S, Seki R. Effects of chlorine, iodine, and quaternary ammonium compound disinfectants on several exotic disease viruses. J Vet Med Sci 2000;62:85-92.
Selvaggi G, Monstrey S, van Landuyt K, Hamdi M, Blondeel P. The role of iodine in antisepsis and wound management: A reappraisal. Acta Chir Belg 2003;103:241-7.
Mangran A, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol 1999;20:247-134.
König B, Reimer K, Fleischer W, König W. Effects of Betaisodona on parameters of host defense. Dermatology 1997;195 Suppl 2:42-8.
Beukelman CJ, van den Berg AJ, Hoekstra MJ, Uhl R, Reimer K, Mueller S. Anti-inflammatory properties of a liposomal hydrogel with povidone-iodine (Repithel) for wound healing in vitro
. Burns 2008;34:845-55.
Sriwilaijaroen N, Wilairat P, Hiramatsu H, Takahashi T, Suzuki T, Ito M, et al
. Mechanisms of the action of povidone-iodine against human and avian influenza A viruses: Its effects on hemagglutination and sialidase activities. Virol J 2009;6:124.
Kumar KS, Reddy GV, Naidu G, Pandiarajan R. Role of povidone iodine in periapical surgeries: Hemostyptic and anti-inflammatory? Ann Maxillofac Surg 2011;1:107-11.
] [Full text]
Arakeri G, Brennan PA. Povidone-iodine: An antioedematous agent? Int J Oral Maxillofac Surg 2011;40:173-6.
Gibbons RJ. Bacterial adhesion to oral tissues: A model for infectious diseases. J Dent Res 1989;68:750-60.
Gibbons RJ, Spinell DM, Skobe Z. Selective adherence as a determinant of the host tropisms of certain indigenous and pathogenic bacteria. Infect Immun 1976;13:238-46.
Lachapelle J, Castel O, Casado F, Leroy B, Micali G, Tennstedt D, et al
. Antiseptics in the era of bacterial resistance: A focus on povidone iodine. Future Med 2013;10:579-92.
Kawana R, Kitamura T, Nakagomi O, Matsumoto I, Arita M, Yoshihara N, et al
. Inactivation of human viruses by povidone-iodine in comparison with other antiseptics. Dermatology 1997;195 Suppl 2:29-35.
Ito H, Ito T, Hikida M, Yashiro J, Otsuka A, Kida H, et al
. Outbreak of highly pathogenic avian influenza in Japan and anti-influenza virus activity of povidone-iodine products. Dermatology 2006;212 Suppl 1:115-8.
Ito H, Hikida M, Yashiro J. Virucidal efficacy of povidone-iodine products against swine influenza viruses. J Chemother 2009;57:508-10.
Kariwa H, Fujii N, Takashima I. Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents. Dermatology (Basel, Switzerland) 2006;212 Suppl: 119-23.
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;7:249-59.
Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, et al
. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020;10:766-88.
Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp Infec 2020;104:246-51.
Reyazulla MA, Gopinath AL, Vaibhav N, Raut RP. An unusual complication of late onset allergic contact dermatitis to povidone iodine in oral & maxillofacial surgery a report of 2 cases. Eur Ann Allergy Clin Immunol 2014;46:157-9.
Dela Cruz F, Brown DH, Leikin JB, Franklin C, Hryhorczuk DO. Iodine absorption after topical administration. West J Med 1987;146:43-5.
Shiraishi T, Nakagawa Y. Evaluation of the bactericidal activity of povidone-iodine and commercially available gargle preparations. Dermatology 2002;204 Suppl 1:37-41.
Ader AW, Paul TL, Reinhardt W, Safran M, Pino S, McArthur W, et al
. Effect of mouth rinsing with two polyvinylpyrrolidone-iodine mixtures on iodine absorption and thyroid function. J Clin Endocrinol Metab 1988;66:632-5.
Ferguson MM, Geddes DA, Wray D. The effect of a povidone-iodine mouthwash upon thyroid function and plaque accumulation. Br Dent J 1978;144:14-6.
Müller G, Kramer A. Comparative study of in vitro
cytotoxicity of povidone-iodine in solution, in ointment or in a liposomal formulation (Repithel) and selected antiseptics. Dermatology 2006;212 Suppl 1:91-3.
Danziger Y, Pertzelan A, Mimouni M. Transient congenital hypothyroidism after topical iodine in pregnancy and lactation. Arch Dis Child 1987;62:295-6.
Amin MS, Harrison RL, Benton TS, Roberts M, Weinstein P. Effect of povidone-iodine on Streptococcus mutans in children with extensive dental caries. Pediatr Dent 2004;26:5-10.
Kanagalingam J, Feliciano R, Hah JH, Labib H, Le TA, Lin JC. Practical use of povidone-iodine antiseptic in the maintenance of oral health and in the prevention and treatment of common oropharyngeal infections. Int J Clin Pract 2015;69:1247-56.
Seymour S. Block disinfections, sterilization and preservation. In: Lee and Fabriger. 4th
ed. Philadelphia, London: Disinfectants and Antiseptics by Chemical Types; 1991. p. 152.
Maruniak J, Clark WB, Walker CB, Magnusson I, Marks RG, Taylor M, et al
. The effect of 3 mouthrinses on plaque and gingivitis development. J Clin Periodontol 1992;19:19-23.
Petersen PE, Bourgeois D, Ogawa H, Estupinan-Day S, Ndiaye C. The global burden of oral diseases and risks to oral health. Bull World Health Organ 2005;83:661-9.
Collins JG, Offenbacher S, Arnold RR. Effects of a combination therapy to eliminate Porphyromonas gingivalis
in refractory periodontitis. J Periodontol 1993;64:998-1007.
Nagatake T, Ahmed K, Oishi K. Prevention of respiratory infections by povidone-iodine gargle. Dermatology 2002;204 Suppl 1:32-6.
Satomura K, Kitamura T, Kawamura T, Shimbo T, Watanabe M, Kamei M, et al
. Prevention of upper respiratory tract infections by gargling: A randomized trial. Am J Prev Med 2005;29:302-7.
Kitamura T, Satomura K, Kawamura T, Yamada S, Takashima K, Suganuma N, et al
. Great cold investigators-I. Can we prevent influenza-like illnesses by gargling? Intern Med 2007;46:1623-4.
Committee for the Japanese Respiratory Society Guidelines in Management of Respiratory. Prevention of hospital-acquired pneumonia (strategies for prevention of hospital-acquired infections). Respirology 2004;9 Suppl 1:S48-50.
Sakai M, Shimbo T, Omata K, Takahashi Y, Satomura K, Kitamura T, et al
. Cost-effectiveness of gargling for the prevention of upper respiratory tract infections. BMC Health Serv Res 2008;8:258.
Farzan A, Firoozi P. Common mouthwash for pre-procedural rinsing in dental practice: Which one is appropriate for eliminating coronaviruses? A mini literature review. Regen Reconst Rest 2020;5:e 2.
Lubomirov D, Petkanchin V. Decontaminating the Nose, Mouth and Throat of SARSCoV-2 with Povidone-Iodine – Aren't We Missing Out on Very Effective Prevention and Prophylactic Tools in the War Against the Covid-19 Pandemic? 2020.