August 18, 2021, preprint. PVPI.pdf
Oronasal Hygiene with PVP-I for COVID19
- Mouth rinsing, gargling, and nasal irrigation with Povidone-Iodine (PVP-I) is safe and effective for prophylaxis, early treatment, and prevention of transmission of COVID-19
- PVP-I has been used for decades as a broad-spectrum antiseptic in dentistry and otolaryngology, so its use for COVID-19 is not re-purposing
- PVP-I has been widely used in India to prevent nosocomial transmission of COVID-19
- In clinical trials, PVP-I was up to 90% in prevention hospitalizations and deaths from COVID-19
Application of 0.5%-1.0% PVP-I solution to the nasal cavity, oral cavity, nasopharynx, and oropharynx, 2-4 times per day, is an excellent prophylaxis and adjuvant treatment of early COVID-19. Its use would also prevent or sharply decrease transmission of the virus from contagious persons. Povidone-Iodine (PVP-I) is available over the counter.
This is the conclusion from the available literature, including physicians’ recommendations.
PVP-I solution has been used as a broad-spectrum antiseptic, effective against viruses, bacteria, fungi, and other pathogens in dentistry and otolaryngology for decades.
PVP-I was introduced in 1955 (Eggers, 2019). It has demonstrated safety and effectiveness against a broad range of throat and mouth pathogens. It was shown effective against SARS and MERS, influenza viruses, and endemic human coronaviruses (Kanagalingam et al., 2015). Thus, the use of PVP-I against SARS-COV-2 is not repurposing.
Gargling with PVP-I was recommended by Japan’s Ministry of (Eggers et al., 2018) (Eggers, 2019) since the 2009 pandemic flu, and by the government of China since the beginning of the COVID-19 pandemic.
This is a narrative review of the literature on the use of PVP-I for prophylaxis and treatment of COVID-19, highlighting the best. All studies from they systematic review (C19 Anonymous, 2021), available on August 13, 2021, have been considered, plus a selection of pre-COVID19 studies and currently available medical protocols as well as doctors’ professional reports.
Protocols, Proposals, and Medical Experience
(FLCCC, 2021) suggests 3x daily gargling and nasal irrigation with 1% PVP-I solution as part of early treatment. Saline solution is for nasal use. 2x daily gargling is proposed for prophylaxis. Listerine and some other antiseptics are also proposed for gargling / mouth washing.
(Marik, 2021) supports (FLCCC, 2021) with a special emphasis on the Delta variant. It also stresses that reducing the viral load in URT is likely to reduce disease severity.
(Arefin, 2021) , (Khan and Parab, 2021) report that many otolaryngology offices in India, including theirs, have asked patients to gargle and to take nasal drops or spray of 0.5%-0.6% PVP-I, before examination and other procedures. They have found that PVP-I is highly tolerable, does not cause tooth stain, and the procedure is practical and useable. They also report that this procedure provided sufficient safety to the personnel and other patients. (Khan and Parab, 2021) report that the protection remains sufficient for 4 hours. (Arefin, 2021) report that the personnel were required to repeat that procedure every 2-3 hours. Such broad and unremarkable use might explain relative paucity of easily accessible papers on the subject.
Doctors at St. Paul’s Sinus Centre are conducting a trial and believe that early sinus rinse and throat gargle with PVP-I would be a game changer in early COVID-19 treatment (Javer (quoted), 2021).
Peer Reviewed literature, trials and in vitro
Nasal and oral cavities, oro- and nasopharynx are primary mucosal surfaces, are occupied by the coronavirus in the first few days of infection (Khan and Parab, 2021). These areas are all connected, and fluids containing it move between them. This suggests that cleansing all the areas at the same time is most beneficial.
The only sufficiently powered clinical trial of PVP-I applied to nasal cavity, nasopharynx, oral cavity, and oropharynx (Choudhury et al., 2021) has shown about 10 times decrease (sic!) in deaths and hospitalization. It used gargle/mouthwash, nasal drops, and eye drops with 1% PVP-I in a large cohort of more than 600 COVID-19 patients. Eye drops do not seem essential.
Multiple trials, using only throat or nasal application of PVP-I have confirmed high efficacy of PVP-I, even when not applied to all the areas previously listed.
(Arefin et al., 2021) reports a clinical trial with nasal application only. Nasal irrigation was found superior to nasal spray. 0.5%-0.6% PVP-I caused viral clearance in 89% (48/54) patients, without adverse effects.
(Seet et al., 2021) reports a clinical trial using a PVP-I throat spray. It observes significant decrease of sickness and symptoms compared with placebo and other treatment groups, in real world conditions.
(Elzein et al., 2021) reports a large decrease of viral load in saliva, after mouthwash with PVP-I, measured in PCR cycles (Ct), necessary for the detection. The decrease corresponded to 4.5 cycles with PVP-I. The use of PCR test probably underestimates the effect, because PCR detects viral RNA. If the amount of viable virus were measured, the decrease would likely be much larger.
Multiple studies (Anderson et al., 2020) (Bidra et al., 2020) show that 0.5% PVP-I inactivates SARS-COV-2 in 15-30 seconds in vitro.
No study, reporting a lack of efficacy of PVP-I against COVID-19 has been encountered. Temporary elevation of thyroid stimulating hormone (an adverse side effect) was observed in a small clinical trial applying excessive amounts of PVP-I (Guenezan et al., 2021).
Peer reviewed literature, reviews
(Chopra et al., 2021) (Frank et al., 2020) review PVP-I activity, mentioning successful inactivation of human CoVs, SARS and MERS in as little as 15 seconds, and recommending 0.5%-1% concentrations.
(Maurya et al., 2021) stresses the use of PVP-I as a second line of defense against COVID-19 in dentistry, describing its safety and tolerability. In agreement with other authors, this paper also recommends that clinical staff use PVP-I every 2-3 hours (up to 4 times a day) and that patients use it before procedures.
Gargling and nasal irrigation has been traditionally used in India. Gargling was officially adopted by Japan and has been used as a traditional remedy in many European countries. However, these are not traditional procedures in the US. This would partly explain the apparent scarcity of research published in English, and the insufficient interest from the physicians. However, the successful outcomes of many clinical trials’ as well as the practical experiences of many doctors, justify the immediate and broad use of PVP-I in COVID-19 prophylaxis and treatment.
Povidone Iodine, 0.5% solution is sold over the counter, under the brand name Betadine. There is also a 10% solution, used topically, for skin issues. For oral, nasal, or pharynx use, it must be diluted to 1% or less (FLCCC, 2021).
PVP-I could possibly be used alongside other OTC prophylactic and therapeutic treatments of limited effectiveness, such as vitamin C, vitamin D, Quercetin, and Zinc, as well as with drugs such as Ivermectin and Hydroxychloroquine.
There are other mouth rinsing / gargling solutions, including Listerine, with efficacy against COVID-19 (Meyers et al., 2021).
Iodine intolerance and thyroid diseases are among some of the contra-indications for PVP-I use.
Studies support the successful use of PVP-I (0.5% – 1.0% solution) to prevent and/or treat COVID-19. The best results were obtained by applying PVP-I to the nasal cavity, nasopharynx, oral cavity, and oropharynx, every 4 hours. The methods were nasal irrigation, mouth rinsing, and gargling. Some may also be applied in spray form. Saline solution is preferable for nasal use.
PVP-I works by inactivating the virus on the mucosal surfaces of the mouth, nasal cavity, and throat. It destroys coronavirus’ envelope and/or membrane. PVP-I inactivates the virus present at the time of application. It also remains on the mucosal surfaces for some time and continues to destroy virus that appears on them from outside and inside.
PVP-I effect might be underestimated when measured by PCR because PVP-I does not act directly on the RNA, measured by PCR tests.
Observed and expected effects:
- PVP-I prevents infection by destroying virus present on the mucosal surfaces at the time of treatment and some time after it.
- PVP-I improves outcomes in the early phase of infection, by preventing or decreasing the spread of the virus from oro- and nasopharynx into the lungs
- PVP-I reduces viral transmission to others, especially in the early stages, when most of the coronavirus load is in the upper respiratory tract (URT)
PVP-I does not prevent the replication of the coronavirus once it has already infected tissues.
In addition to prophylaxis and treatment of COVID-19, PVP-I can be used for protection of healthcare workers; as a broad acting antiviral with monoclonal antibodies treatment; and as a quick prophylaxis before or after exposure to COVID-19.
No Competing Interests
The author declares no competing interest. No funding was provided for this work.
This is not medical advice.
Anderson, D.E., Sivalingam, V., Kang, A.E.Z., Ananthanarayanan, A., Arumugam, H., Jenkins, T.M., Hadjiat, Y., Eggers, M., 2020. Povidone-Iodine Demonstrates Rapid In Vitro Virucidal Activity Against SARS-CoV-2, The Virus Causing COVID-19 Disease. Infect Dis Ther 9, 669–675. https://doi.org/10.1007/s40121-020-00316-3
Arefin, M.K., 2021. Povidone Iodine (PVP-I) Oro-Nasal Spray: An Effective Shield for COVID-19 Protection for Health Care Worker (HCW), for all. Indian J Otolaryngol Head Neck Surg 1–6. https://doi.org/10.1007/s12070-021-02525-9
Arefin, M.K., Rumi, S.K.N.F., Uddin, A.K.M.N., Banu, S.S., Khan, M., Kaiser, A., Chowdhury, J.A., Khan, Md.A.S., Hasan, M.J., 2021. Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: an open-label randomized clinical trial. Indian J Otolaryngol Head Neck Surg. https://doi.org/10.1007/s12070-021-02616-7
Bidra, A.S., Pelletier, J.S., Westover, J.B., Frank, S., Brown, S.M., Tessema, B., 2020. Rapid In-Vitro Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Using Povidone-Iodine Oral Antiseptic Rinse. Journal of Prosthodontics 29, 529–533. https://doi.org/10.1111/jopr.13209
C19 Anonymous, A., 2021. PVP-I for COVID-19: real-time analysis of all 17 studies. https://c19pvpi.com
Chopra, A., Sivaraman, K., Radhakrishnan, R., Balakrishnan, D., Narayana, A., 2021. Can povidone iodine gargle/mouthrinse inactivate SARS-CoV-2 and decrease the risk of nosocomial and community transmission during the COVID-19 pandemic? An evidence-based update. Japanese Dental Science Review 57, 39–45. https://doi.org/10.1016/j.jdsr.2021.03.001
Choudhury, M.I.M., Shabnam, N., Ahsan, T., Kabir, M.S., Ahsan, R.M.K. and S.M.A., 2021. Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal and Eye Drop in COVID-19 patient. Bioresearch Communications-(BRC) 7, 919–923. https://www.bioresearchcommunications.com/index.php/brc/article/view/176
Eggers, M., 2019. Infectious Disease Management and Control with Povidone Iodine. Infect Dis Ther 8, 581–593. https://doi.org/10.1007/s40121-019-00260-x
Eggers, M., Koburger-Janssen, T., Eickmann, M., Zorn, J., 2018. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens. Infect Dis Ther 7, 249–259. https://doi.org/10.1007/s40121-018-0200-7
Elzein, R., Abdel-Sater, F., Fakhreddine, S., Hanna, P.A., Feghali, R., Hamad, H., Ayoub, F., 2021. In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2. A randomized-controlled clinical trial. Journal of Evidence Based Dental Practice 21, 101584. https://doi.org/10.1016/j.jebdp.2021.101584
FLCCC, 2021. I-MASK+ Protocol. FLCCC | Front Line COVID-19 Critical Care Alliance. URL https://covid19criticalcare.com/covid-19-protocols/i-mask-plus-protocol/
Frank, S., Capriotti, J., Brown, S.M., Tessema, B., 2020. Povidone-Iodine Use in Sinonasal and Oral Cavities: A Review of Safety in the COVID-19 Era. Ear Nose Throat J 99, 586–593. https://doi.org/10.1177/0145561320932318
Guenezan, J., Garcia, M., Strasters, D., Jousselin, C., Lévêque, N., Frasca, D., Mimoz, O., 2021. Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial. JAMA Otolaryngology–Head & Neck Surgery 147, 400–401. https://doi.org/10.1001/jamaoto.2020.5490
Javer (quoted), A., 2021. Researchers investigate iodine rinse as treatment for COVID-19 The Daily Scan. https://thedailyscan.providencehealthcare.org/2021/06/iodine-rinse-as-treatment-for-covid-19/
Kanagalingam, J., Feliciano, R., Hah, J.H., Labib, H., Le, T.A., Lin, J.-C., 2015. Practical use of povidone-iodine antiseptic in the maintenance of oral health and in the prevention and treatment of common oropharyngeal infections. International Journal of Clinical Practice 69, 1247–1256. https://doi.org/10.1111/ijcp.12707
Khan, M.M., Parab, S.R., 2021. Tolerability and usability of 0.5% PVP-I gargles and nasal drops in 6692 patients: Observational study. Am J Otolaryngol 42, 102880. https://doi.org/10.1016/j.amjoto.2020.102880
Marik, P., 2021. An overview of the MATH+, I-MASK+ and I-RECOVER Protocols. A Guide to the Management of COVID-19. https://covid19criticalcare.com/wp-content/uploads/2020/12/FLCCC-Protocols-%E2%80%93-A-Guide-to-the-Management-of-COVID-19.pdf
Maurya, R.K., Singh, H., Kapoor, P., Sharma, P., Srivastava, D., 2021. Povidone-iodine preprocedural rinse—An evidence-based, second-line defense against severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in dental healthcare. Infection Control & Hospital Epidemiology 1–2. https://doi.org/10.1017/ice.2021.90
Meyers, C., Robison, R., Milici, J., Alam, S., Quillen, D., Goldenberg, D., Kass, R., 2021. Lowering the transmission and spread of human coronavirus. Journal of Medical Virology 93, 1605–1612. https://doi.org/10.1002/jmv.26514
Seet, R.C.S., Quek, A.M.L., Ooi, D.S.Q., Sengupta, S., Lakshminarasappa, S.R., Koo, C.Y., So, J.B.Y., Goh, B.C., Loh, K.S., Fisher, D., Teoh, H.L., Sun, J., Cook, A.R., Tambyah, P.A., Hartman, M., 2021. Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: An open-label randomized trial. International Journal of Infectious Diseases 106, 314–322. https://doi.org/10.1016/j.ijid.2021.04.035
via Science Defies Politics
August 18, 2021