Bioresearch Communications

Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal Volume 7, Issue 1, January 2021

and Eye Drop in COVID-19 patient
Md. Iqbal Mahmud Choudhury1, Nilufar Shabnam2, Tazin Ahsan3, Md. Saiful kabir4,
Rashed Md. Khan5, S.M. Abu Ahsan6
1
Assistant professor, Plastic Surgery Unit, Department of Surgery, Bangabandhu Sheikh Mujib Medical
2
University, Shahbag, Dhaka, Bangladesh. Assistant professor, Department of Surgery, BIRDEM Hospital &
3
Ibrahim Medical College, Shahbag, Dhaka, Bangladesh. Medical officer, Upazila Health Complex,
4
Chowgacha, Jessore, Bangladesh. Professor and Head, Department of Dermatology and Venereology,
5
National Medical College, Dhaka, Bangladesh. Professor and Head, Department of Dermatology and
6
Venereology, Dhaka Medical College, Dhaka, Bangladesh. Associate Professor and Head, Ad-din Sakina
Medical college, Jessore, Bangladesh.

ABSTRACT: Background: The sudden onset of COVID-19 began in late 2019 caused by a novel coronavirus (SARS-COV2) and on 11th March, WHO
declared it to have developed pandemic status. There is still no specific treatment and vaccine available for COVID-19; causing wide spread health
problem and concern of the globe. Povidone iodine (PVP-I) is an antiseptic that has been used for over 150 years. It is already proved that different
concentration of PVP-I can deactivate COVID-19 virus. Methodology: In this randomized controlled clinical trial, out of 1113 patients 606 patients
were enrolled and divided in 2 groups by randomization after taken consents. In Gr-A, 303 patients underwent mouthwash/gargle, nasal drops and
eye drops with 1% povidone iodine 4 hourly for 4 weeks as well as symptomatic treatment according to need. In Gr-B 303 patients were advised
mouthwash/gargle, nasal cavity and eye wash with lukewarm water 4 hourly for 4 weeks and symptomatic treatment according to need. RT-PCR
test done every 3rd, 5th and 7th day and Thyroid hormone level (TSH,T3, T4, FT4) at 4th week for follow up. Results: The group of patients used 1%
PVP-I have shown tremendously reduced mortality, morbidity and hospital as well as financial burden in this covid situation. Conclusion:
Administration of 1% PVP-I as mouthwash/gargle, nasal or eye drop is simple, rapid and cost effective in reduction of mortality and morbidity by
COVID-19.

KEYWORDS: Povidone Iodine, 1Pq.s, COVID-19.

RECEIVED: 07 September 2020, ACCEPTED: 03 December 2020 CORRESPONDING AUTHOR: Dr. Md. Iqbal Mahmud Choudhury, assistant
professor, Plastic Surgery Unit, Department of Surgery, Bangabandhu
TYPE: Original Research
Sheikh Mujib Medical University, Shahbag, Dhaka.
Email: [email protected] Mobile: +8801713011283

Introduction study done by Hou et al. shows that the ciliated cell with
A strange situation has emerged among the people all over the ACE2 expressions are most susceptible to infection which are
world due to corona virus disease (COVID-19) due to its more in the upper than lower air way cells.9 The study shows
presence for uncertain time and severity of its consequences. that a virus transmission pathway, which involves infection of
Since December 2019, scientists and health-care workers are ciliated cells of upper airway (nasal cavity) is the commonest
struggling for effective treatment plan and implementing site of infection followed by subsequent aspiration to lower
strategies to control this pandemic. The nasal cavity, airway and secondary to lungs. This process may play a role in
oropharynx and nasopharynx are the initial target cell of novel systemic involvement and variable expression of clinical
corona virus with the result saliva contains high viral load of severity.10,11,12 Iodine is an effective anti-septic agent since
COVID-19 with upto1.2 X108 infective copies/ml.1,2,3 The 1800s. Povidone Iodine was discovered in 1955 by H.A.
saliva is an important diagnostic tool for rapid mass Shelanski and M.V. Shelanski. It is a water soluble polymer
detection.4 COVID-19 virus occupies host cells through two polyvinyl pyrrotodon (PVP-I) and less toxic than tincture of
receptors: Angiotensin Converting Enzyme 2 (ACE2) and iodine.13 PVP-I is extensively used as a hand washing agent
CD147 (Basigen or EMMPRIN). Viral spike protein (SP) fixes (as a 7.5% solution), for pre-procedure skin preparation (as a
to ACE2 or CD147 of host cell causing viral invasion, 10% solution), in ophthalmic surgery (as a 5% solution) and in
replication and spreading to other cells.5,6 Like RBCs and oral surgery (as a 10% solution).14,15,16 PVP-I is commercially
Type-II alveolar cells (AT2 ) of lung. CD147 is also present in available in Asia as a 1% w/v mouthwash for use every 2-
tear, alveolar tissues and retinal pigmented epithelium.7 So 4hourly. 17 The onset of antiseptic action of PVP-I starts when
some sort of upper respiratory tract infection is due to binding free form of iodine dissociate from the polymer complex
of COVID-19 virus with CD147 in ocular tissues then travel which rapidly penetrates the microbes oxidizing the nucleic
into nasal cavity via naso-lacrimal duct.5,6 In case of COVID- acid and its protein structures. PVP-I has higher virucidal
19, initial interaction between its host receptor (ACE 2 or activity than other commonly used anti-septic agents like
CD147) and spike protein (SP) are the initiating event in chlorhexidine and benzalkonium chloride and shown to be
establishment of causing human host infection. 8 A recent active in vitro against SARS-COV (epidemic of 2002-03) &
920 Effect of 1% Povidone Iodine Mouthwash

MERS-COV (epidemic of 2012-13) virus.18,19,20 COVID-19 required hospitalization were admitted in of Anwar Khan
Virus is highly homologous to SARS virus.21 In vitro study on Modern Medical College Hospital. The study protocol was
virucidal activity of povidone iodine against MERS & SARS approved by the ethical committee of Anwar Khan Modern
virus show that the lowest concentration of povidone iodine to Medical College Hospital. Analysis was performed by using a
effective was 1% when used for 30 seconds, leading to a computer based statistical program SPSS (Statistical Package
reduction of viral activity of ≥ 99.99%.22 So, 1% PVP-I for Social Sciences) version 16. Quantitative data were
solution as mouthwash/gargle, nasal drop/spray and eye drop expressed as means ±SD. 95% confidence interval was
inactivate the heam agglutinin esterase activity as well as calculated and p value of <0.05 was considered as
enhance absorption of ACE2 as receptor of host cell.23 Thus significance.
reduced the infectivity of host with systemic transmission and Preparation and Method of Application of 1% PVP-I –
as well as cross infection. 10% PVP-I is found all over the country. But 1%
commercially available PVP-I is found only in a few cities or
Materials and Methods town. Most of the 1% PVP-I was formed from 10% PVP-I in
Total 1113 patients from 1st February 2020 to 30th August the following manner - Povidone Iodine 1P 10% v/w in
2020 in Bangladesh took treatment through telemedicine purified water 1P q.s. Therefore, use 1 mL of PVP-I in 10mL
service of Anwar Khan Modern Medical College Hospital, of sterile water/purified water. 1% PVP-I is introduced into
Call A Doctor BD, Sebaghar. All patients were highly oral cavity as mouth wash. Care is taken to ensure the solution
educated and belong to middle class family. They had very is distributed throughout the oral cavity for 30 seconds and
much hospital phobia in COVID-19 situation and wanted to then gently gargled or, held at the back of the throat for
take treatment at home isolation rather than in hospital. We another 30 seconds before spitting out. Then 4-5 drops of 1%
used mobile calls, Viber, WhatsApp, e-mail and Zoom for PVP-I is introduced to wash the nostrils by dropper and 2
communication and collection of data from patient or drops in each eye. This application is done 4 hourly for 4
attending relative. RT-PCR positive patients who have done weeks.
the test on 1st day of symptom (single or multiple symptoms –
fever, body ache, headache, loss of smell, loss of taste, sore Results
throat, diarrhea, skin rash, shortness of breath, redness of the In the study, more affected are male (79.87 %, N- 484) than
eyes), age more than 10 years and less than 90 years were female (20.13%, N- 122). The differences were not
included in this study. Patients with history of allergy to statistically significant (P>0.05). More (39.93%) patients are
povidone iodine, all form of thyroid diseases or on radioactive in the 31-50 years age group, followed by 34.65% in the 51-70
iodine treatment, known pregnancy, renal failure and years age group (Table -1). In group A (patients used PVP-I),
malignancy were excluded. 606 patients were enrolled and only 2.64% (N-8) patient is RT-PCR positive on the 7th day
divided in 2 groups by randomization after taken consents. In whereas in group B (patients used lukewarm water), it is
Gr-A, 303 patients underwent mouthwash/gargle, nasal drops 70.30% (N-213) (Table 2, Gr- A & B) (p>0.05). Data of Table
and eye drops with 1% povidone iodine 4 hourly for 4 weeks 3(Gr-A&B) shows that 3.30% (N-10) hospitalized patients of
as well as symptomatic treatment according to need. In Gr-B, group A needed oxygen support (by mechanical ventilator
303 patients were advised mouthwash/gargle, nasal cavity and and/or high flow nasal cannula and/or non rebreather mask
eye wash with lukewarm water 4 hourly for 4 weeks and and/or face mask and/or nasal cannula) but 20.79% (N-63)
symptomatic treatment according to need. RT-PCR test done patients of group B needed oxygen support. Mortality rate is
every 3rd, 5th and 7th day and Thyroid hormone level high 5.6% (N-17) in group B than 0.66% (N-2) in group A.
(TSH,T3, T4,FT4) at 4th week for follow up. Some patients The differences were statistically significant (P<0.05).

Table-1. Age and Sex Distributions of patients

Age Group(yrs) Male Female Total

11-30 72 11.88% 18 2.97% 90 14.85%
31-50 193 31.85% 49 8.09% 242 39.93%
51-70 167 27.56% 43 7.10% 210 34.65%
71-90 52 8.58% 12 1.98% 64 10.56%
484 79.87% 122 20.13% 606 100%

Table-2. Gr-A( RT-PCR test result using PVP-I)

RT-PCR test positive on 3rd RT-PCR test positive on 5th RT-PCR test positive on 7th
Age Group day day day
(yrs) Male Female Male Female Male Female
11-30 2 1 1 0 0 0
31-50 6 3 4 2 0 1
51-70 7 5 6 3 2 1
71-90 7 4 5 3 3 1
22 (7.26%) 13 (4.29%) 16 (5.25%) 8 (2.64%) 5 (1.65%) 3 (0.99%)
35 (11.55%) 24 (7.92%) 8 (2.64%)
Choudhury et. al. 921

Table-2. Gr-B (RT-PCR test result using lukewarm water)

RT-PCR test positive on 3rd RT-PCR test positive on 5th RT-PCR test positive on 7th
Age Group day day day
(yrs) Male Female Male Female Male Female
11-30 33 9 29 6 20 3
31-50 95 23 91 19 81 15
51-70 80 20 77 18 62 12
71-90 26 75 24 4 18 2
235 (77.22%) 57(18.81%) 221(72.937%) 47(15.51%) 181(59.735%) 32(10.56%)
291 (96.039 %) 268 (88.448%) 213 (70.297%)

Table-3. Gr-A (Total outcome after using PVP-I)

Hospitalized Hospitalized + Oxygen support Death

Age Group Male Female Male Female Male Female
(yrs)
11-30 0 0 0 0 0 0
31-50 1 0 0 0 0 0
51-70 0 0 4 1 1 0
71-90 1 0 3 2 1 0
2 (0.66%) 0 7 (2.31%) 3 (0.99%) 2 (0.66%) 0
2 (0.66%) 10(3.30%) 2 (0.66%)

Table-3. Gr-B (Total outcome after using lukewarm water)

Hospitalized Hospitalized + Oxygen support Death

Age Group Male Female Male Female Male Female
(yrs)
11-30 0 0 7 1 0 0
31-50 5 2 16 5 3 1
51-70 5 0 11 9 6 0
71-90 1 1 9 5 5 2
11 (3.63%) 3 (0.99%) 43 (14.19%) 20 (6.60%) 14 (4.62%) 3(0.99%)
14 (4.62%) 63 (20.79%) 17 (5.61%)

Discussion 99.99% virucidal activity against COVID-19 was found for a

There are no established effective therapies or vaccines for 1% PVP-I mouth wash and a 0.45% PVP-I throat spray.35
COVID-19 infection still today, so treatment relies mostly on COVID-19 viral load are high in nasal cavity, naso-
supportive care, oxygen support with or without mechanical oropharynx, lymphocyte of oral tissues, goblet and ciliated
ventilation and medication previously employed against cells within respiratory epithelium of nose have the highest
SARS-Cov, MARS-Cov.24Povidone Iodine (PVP-I) is very expression of ACE2, the main receptor of COVID-19 virus
much effective virucidal and well tolerable mouthwash/ and some accidental ocular exposure CD147, also receptor of
gargle, nasal spray and eye drop than other antiseptics which COVID-19 virus.36 PVP-I of 0.5-10% solution inactivate the
working against SARC-Cov and MARS-Cov is already ACE2 and CD147 receptor of host cell. In our study, patients of
proven.25,26 Free iodine release from aqueous solution of PVP- Gr-A (those who used 1% PVP-I) are tremendously improved
I which likely attack surface proteins of enveloped virus and over Gr-B (those who used only lukewarm water) in terms of
destabilizes membrane fatty acid by reacting with unsaturated RT-PCR test result, mortality, hospitalization with or without
carbon bond. 27,28,29,30 It is already proved that binding with oxygen support (Table-2&3). In table-2, only 11.55% patient’s
iodine to the lipid component of enveloped virus increases show RT-PCR test positive in Gr-A on 3rd day where as
susceptibility over non enveloped viruses.31 COVID-19 virus 96.04% is positive in Gr-B. On the other hand, 2.64% patient
belongs to a family of enveloped, single-stranded RNA corona is positive on 7th day in Gr-A and 70.30% positive in Gr-B.
virus.32 Some recent studies has shown that PVP-I inactivate So, it is clear that 1% PVP-I can vigorously reduce the viral
MERS-Cov and SARS-Cov which has nearly identical load in oral cavity, nasal cavity and naso-oropharynx. This
genomes to COVID-19 virus.33 Concentration of 0.23-1% information is also supported by an in vivo study done by
PVP-I reduced infectivity below detectable level within 2 Martinez Lams et al in June 2020; aimed to determine the
minutes.34 In recent months, susceptibility to PVP-I solutions influence of 1% PVP-I on COVID-19 positive patients. 37
has been confirmed for COVID-19 virus. After 30 seconds, ≥ They evaluated and compared the viral load of the saliva of
922 Effect of 1% Povidone Iodine Mouthwash

those patients after 1 minute use of 1% PVP-I and effects 7. Parikh SR, Bly RA, Bonilla-Velez J, Dahl JP, Evans SS, Horn DL,
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0.66% mortality over 5.61% of Gr-B and only 3.30% exposure. Otolaryngology–Head and Neck Surgery. 2020:
p.0194599820919748.
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comparison to 20.79% in Gr-B. So the patients those who used 8. Sarma P, Prajapat M, Avti P, Kaur H, Kumar S and Medhi B.
1% PVP–I have minimum mortality, morbidity and occupying Therapeutic options for the treatment of 2019-novel coronavirus: An
minimum number of hospital bed causing less burden to health evidence-based approach. Indian journal of pharmacology. 2020;
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